@baimingtao/lbs-agent 1.0.0

package/extensions/skills/optional/research/domain-intel/scripts/domain_intel.py

@@ -0,0 +1,397 @@
+#!/usr/bin/env python3
+"""
+Domain Intelligence — Passive OSINT via Python stdlib.
+
+Usage:
+    python domain_intel.py subdomains example.com
+    python domain_intel.py ssl example.com
+    python domain_intel.py whois example.com
+    python domain_intel.py dns example.com
+    python domain_intel.py available example.com
+    python domain_intel.py bulk example.com github.com google.com --checks ssl,dns
+
+All output is structured JSON. No dependencies beyond Python stdlib.
+Works on Linux, macOS, and Windows.
+"""
+
+import json
+import re
+import socket
+import ssl
+import sys
+import urllib.request
+import urllib.parse
+from concurrent.futures import ThreadPoolExecutor, as_completed
+from datetime import datetime, timezone
+
+
+# ─── 子域名发现 (crt.sh) ──────────────────────────────────────────
+
+def subdomains(domain, include_expired=False, limit=200):
+    """Find subdomains via Certificate Transparency logs."""
+    url = f"https://crt.sh/?q=%25.{urllib.parse.quote(domain)}&output=json"
+    req = urllib.request.Request(url, headers={
+        "User-Agent": "domain-intel-skill/1.0", "Accept": "application/json",
+    })
+    with urllib.request.urlopen(req, timeout=15) as r:
+        entries = json.loads(r.read().decode())
+
+    seen, results = set(), []
+    now = datetime.now(timezone.utc)
+    for e in entries:
+        not_after = e.get("not_after", "")
+        if not include_expired and not_after:
+            try:
+                dt = datetime.strptime(not_after[:19], "%Y-%m-%dT%H:%M:%S").replace(tzinfo=timezone.utc)
+                if dt <= now:
+                    continue
+            except ValueError:
+                pass
+        for name in e.get("name_value", "").splitlines():
+            name = name.strip().lower()
+            if name and name not in seen:
+                seen.add(name)
+                results.append({
+                    "subdomain": name,
+                    "issuer": e.get("issuer_name", ""),
+                    "not_after": not_after,
+                })
+
+    results.sort(key=lambda r: (r["subdomain"].startswith("*"), r["subdomain"]))
+    return {"domain": domain, "count": min(len(results), limit), "subdomains": results[:limit]}
+
+
+# ─── SSL 证书检查 ────────────────────────────────────────────
+
+def check_ssl(host, port=443, timeout=10):
+    """Inspect the TLS certificate of a host."""
+    def flat(rdns):
+        r = {}
+        for rdn in rdns:
+            for item in rdn:
+                if isinstance(item, (list, tuple)) and len(item) == 2:
+                    r[item[0]] = item[1]
+        return r
+
+    def parse_date(s):
+        for fmt in ("%b %d %H:%M:%S %Y %Z", "%b  %d %H:%M:%S %Y %Z"):
+            try:
+                return datetime.strptime(s, fmt).replace(tzinfo=timezone.utc)
+            except ValueError:
+                pass
+        return None
+
+    warning = None
+    try:
+        ctx = ssl.create_default_context()
+        with socket.create_connection((host, port), timeout=timeout) as sock:
+            with ctx.wrap_socket(sock, server_hostname=host) as s:
+                cert, cipher, proto = s.getpeercert(), s.cipher(), s.version()
+    except ssl.SSLCertVerificationError as e:
+        warning = str(e)
+        ctx = ssl.create_default_context()
+        ctx.check_hostname = False
+        ctx.verify_mode = ssl.CERT_NONE
+        with socket.create_connection((host, port), timeout=timeout) as sock:
+            with ctx.wrap_socket(sock, server_hostname=host) as s:
+                cert, cipher, proto = s.getpeercert(), s.cipher(), s.version()
+
+    not_after = parse_date(cert.get("notAfter", ""))
+    now = datetime.now(timezone.utc)
+    days = (not_after - now).days if not_after else None
+    is_expired = days is not None and days < 0
+
+    if is_expired:
+        status = f"EXPIRED ({abs(days)} days ago)"
+    elif days is not None and days <= 14:
+        status = f"CRITICAL — {days} day(s) left"
+    elif days is not None and days <= 30:
+        status = f"WARNING — {days} day(s) left"
+    else:
+        status = f"OK — {days} day(s) remaining" if days is not None else "unknown"
+
+    return {
+        "host": host, "port": port,
+        "subject": flat(cert.get("subject", [])),
+        "issuer": flat(cert.get("issuer", [])),
+        "subject_alt_names": [f"{t}:{v}" for t, v in cert.get("subjectAltName", [])],
+        "not_before": parse_date(cert.get("notBefore", "")).isoformat() if parse_date(cert.get("notBefore", "")) else "",
+        "not_after": not_after.isoformat() if not_after else "",
+        "days_remaining": days, "is_expired": is_expired, "expiry_status": status,
+        "tls_version": proto,
+        "cipher_suite": cipher[0] if cipher else None,
+        "serial_number": cert.get("serialNumber", ""),
+        "verification_warning": warning,
+    }
+
+
+# ─── WHOIS 查询 ──────────────────────────────────────────────────
+
+WHOIS_SERVERS = {
+    "com": "whois.verisign-grs.com", "net": "whois.verisign-grs.com",
+    "org": "whois.pir.org", "io": "whois.nic.io", "co": "whois.nic.co",
+    "ai": "whois.nic.ai", "dev": "whois.nic.google", "app": "whois.nic.google",
+    "tech": "whois.nic.tech", "shop": "whois.nic.shop", "store": "whois.nic.store",
+    "online": "whois.nic.online", "site": "whois.nic.site", "cloud": "whois.nic.cloud",
+    "digital": "whois.nic.digital", "media": "whois.nic.media", "blog": "whois.nic.blog",
+    "info": "whois.afilias.net", "biz": "whois.biz", "me": "whois.nic.me",
+    "tv": "whois.nic.tv", "cc": "whois.nic.cc", "ws": "whois.website.ws",
+    "uk": "whois.nic.uk", "co.uk": "whois.nic.uk", "de": "whois.denic.de",
+    "nl": "whois.domain-registry.nl", "fr": "whois.nic.fr", "it": "whois.nic.it",
+    "es": "whois.nic.es", "pl": "whois.dns.pl", "ru": "whois.tcinet.ru",
+    "se": "whois.iis.se", "no": "whois.norid.no", "fi": "whois.fi",
+    "ch": "whois.nic.ch", "at": "whois.nic.at", "be": "whois.dns.be",
+    "cz": "whois.nic.cz", "br": "whois.registro.br", "ca": "whois.cira.ca",
+    "mx": "whois.mx", "au": "whois.auda.org.au", "jp": "whois.jprs.jp",
+    "cn": "whois.cnnic.cn", "in": "whois.inregistry.net", "kr": "whois.kr",
+    "sg": "whois.sgnic.sg", "hk": "whois.hkirc.hk", "tr": "whois.nic.tr",
+    "ae": "whois.aeda.net.ae", "za": "whois.registry.net.za",
+    "space": "whois.nic.space", "zone": "whois.nic.zone", "ninja": "whois.nic.ninja",
+    "guru": "whois.nic.guru", "rocks": "whois.nic.rocks", "live": "whois.nic.live",
+    "game": "whois.nic.game", "games": "whois.nic.games",
+}
+
+
+def whois_lookup(domain):
+    """Query WHOIS servers for domain registration info."""
+    parts = domain.split(".")
+    server = WHOIS_SERVERS.get(".".join(parts[-2:])) or WHOIS_SERVERS.get(parts[-1])
+    if not server:
+        return {"error": f"No WHOIS server for .{parts[-1]}"}
+
+    try:
+        with socket.create_connection((server, 43), timeout=10) as s:
+            s.sendall((domain + "\r\n").encode())
+            chunks = []
+            while True:
+                c = s.recv(4096)
+                if not c:
+                    break
+                chunks.append(c)
+            raw = b"".join(chunks).decode("utf-8", errors="replace")
+    except Exception as e:
+        return {"error": str(e)}
+
+    patterns = {
+        "registrar": r"(?:Registrar|registrar):\s*(.+)",
+        "creation_date": r"(?:Creation Date|Created|created):\s*(.+)",
+        "expiration_date": r"(?:Registry Expiry Date|Expiration Date|Expiry Date):\s*(.+)",
+        "updated_date": r"(?:Updated Date|Last Modified):\s*(.+)",
+        "name_servers": r"(?:Name Server|nserver):\s*(.+)",
+        "status": r"(?:Domain Status|status):\s*(.+)",
+        "dnssec": r"DNSSEC:\s*(.+)",
+    }
+    result = {"domain": domain, "whois_server": server}
+    for key, pat in patterns.items():
+        matches = re.findall(pat, raw, re.IGNORECASE)
+        if matches:
+            if key in {"name_servers", "status"}:
+                result[key] = list(dict.fromkeys(m.strip().lower() for m in matches))
+            else:
+                result[key] = matches[0].strip()
+
+    for field in ("creation_date", "expiration_date", "updated_date"):
+        if field in result:
+            for fmt in ("%Y-%m-%dT%H:%M:%S", "%Y-%m-%dT%H:%M:%SZ", "%Y-%m-%d %H:%M:%S", "%Y-%m-%d"):
+                try:
+                    dt = datetime.strptime(result[field][:19], fmt).replace(tzinfo=timezone.utc)
+                    result[field] = dt.isoformat()
+                    if field == "expiration_date":
+                        days = (dt - datetime.now(timezone.utc)).days
+                        result["expiration_days_remaining"] = days
+                        result["is_expired"] = days < 0
+                    break
+                except ValueError:
+                    pass
+    return result
+
+
+# ─── DNS 记录 ───────────────────────────────────────────────────
+
+def dns_records(domain, types=None):
+    """Resolve DNS records using system DNS + Google DoH."""
+    if not types:
+        types = ["A", "AAAA", "MX", "NS", "TXT", "CNAME"]
+    records = {}
+
+    for qtype in types:
+        if qtype == "A":
+            try:
+                records["A"] = list(dict.fromkeys(
+                    i[4][0] for i in socket.getaddrinfo(domain, None, socket.AF_INET)
+                ))
+            except Exception:
+                records["A"] = []
+        elif qtype == "AAAA":
+            try:
+                records["AAAA"] = list(dict.fromkeys(
+                    i[4][0] for i in socket.getaddrinfo(domain, None, socket.AF_INET6)
+                ))
+            except Exception:
+                records["AAAA"] = []
+        else:
+            url = f"https://dns.google/resolve?name={urllib.parse.quote(domain)}&type={qtype}"
+            try:
+                req = urllib.request.Request(url, headers={"User-Agent": "domain-intel-skill/1.0"})
+                with urllib.request.urlopen(req, timeout=10) as r:
+                    data = json.loads(r.read())
+                records[qtype] = [
+                    a.get("data", "").strip().rstrip(".")
+                    for a in data.get("Answer", []) if a.get("data")
+                ]
+            except Exception:
+                records[qtype] = []
+
+    return {"domain": domain, "records": records}
+
+
+# ─── 域名可用性检查 ─────────────────────────────────────────────
+
+def check_available(domain):
+    """Check domain availability using passive signals (DNS + WHOIS + SSL)."""
+    signals = {}
+
+    # DNS
+    try:
+        a = [i[4][0] for i in socket.getaddrinfo(domain, None, socket.AF_INET)]
+    except Exception:
+        a = []
+
+    try:
+        ns_url = f"https://dns.google/resolve?name={urllib.parse.quote(domain)}&type=NS"
+        req = urllib.request.Request(ns_url, headers={"User-Agent": "domain-intel-skill/1.0"})
+        with urllib.request.urlopen(req, timeout=10) as r:
+            ns = [x.get("data", "") for x in json.loads(r.read()).get("Answer", [])]
+    except Exception:
+        ns = []
+
+    signals["dns_a"] = a
+    signals["dns_ns"] = ns
+    dns_exists = bool(a or ns)
+
+    # SSL
+    ssl_up = False
+    try:
+        ctx = ssl.create_default_context()
+        ctx.check_hostname = False
+        ctx.verify_mode = ssl.CERT_NONE
+        with socket.create_connection((domain, 443), timeout=3) as s:
+            with ctx.wrap_socket(s, server_hostname=domain):
+                ssl_up = True
+    except Exception:
+        pass
+    signals["ssl_reachable"] = ssl_up
+
+    # WHOIS (快速检查)
+    tld = domain.rsplit(".", 1)[-1]
+    server = WHOIS_SERVERS.get(tld)
+    whois_avail = None
+    whois_note = ""
+    if server:
+        try:
+            with socket.create_connection((server, 43), timeout=10) as s:
+                s.sendall((domain + "\r\n").encode())
+                raw = b""
+                while True:
+                    c = s.recv(4096)
+                    if not c:
+                        break
+                    raw += c
+                raw = raw.decode("utf-8", errors="replace").lower()
+            if any(p in raw for p in ["no match", "not found", "no data found", "status: free"]):
+                whois_avail = True
+                whois_note = "WHOIS: not found"
+            elif "registrar:" in raw or "creation date:" in raw:
+                whois_avail = False
+                whois_note = "WHOIS: registered"
+            else:
+                whois_note = "WHOIS: inconclusive"
+        except Exception as e:
+            whois_note = f"WHOIS error: {e}"
+
+    signals["whois_available"] = whois_avail
+    signals["whois_note"] = whois_note
+
+    if not dns_exists and whois_avail is True:
+        verdict, conf = "LIKELY AVAILABLE", "high"
+    elif dns_exists or whois_avail is False or ssl_up:
+        verdict, conf = "REGISTERED / IN USE", "high"
+    elif not dns_exists and whois_avail is None:
+        verdict, conf = "POSSIBLY AVAILABLE", "medium"
+    else:
+        verdict, conf = "UNCERTAIN", "low"
+
+    return {"domain": domain, "verdict": verdict, "confidence": conf, "signals": signals}
+
+
+# ─── 批量分析 ─────────────────────────────────────────────────
+
+COMMAND_MAP = {
+    "subdomains": subdomains,
+    "ssl": check_ssl,
+    "whois": whois_lookup,
+    "dns": dns_records,
+    "available": check_available,
+}
+
+
+def bulk_check(domains, checks=None, max_workers=5):
+    """Run multiple checks across multiple domains in parallel."""
+    if not checks:
+        checks = ["ssl", "whois", "dns"]
+
+    def run_one(d):
+        entry = {"domain": d}
+        for check in checks:
+            fn = COMMAND_MAP.get(check)
+            if fn:
+                try:
+                    entry[check] = fn(d)
+                except Exception as e:
+                    entry[check] = {"error": str(e)}
+        return entry
+
+    results = []
+    with ThreadPoolExecutor(max_workers=min(max_workers, 10)) as ex:
+        futures = {ex.submit(run_one, d): d for d in domains[:20]}
+        for f in as_completed(futures):
+            results.append(f.result())
+
+    return {"total": len(results), "checks": checks, "results": results}
+
+
+# ─── CLI 入口点 ───────────────────────────────────────────────
+
+def main():
+    if len(sys.argv) < 3:
+        print(__doc__)
+        sys.exit(1)
+
+    command = sys.argv[1].lower()
+    args = sys.argv[2:]
+
+    if command == "bulk":
+        # 解析 --checks 标志
+        checks = None
+        domains = []
+        i = 0
+        while i < len(args):
+            if args[i] == "--checks" and i + 1 < len(args):
+                checks = [c.strip() for c in args[i + 1].split(",")]
+                i += 2
+            else:
+                domains.append(args[i])
+                i += 1
+        result = bulk_check(domains, checks)
+    elif command in COMMAND_MAP:
+        result = COMMAND_MAP[command](args[0])
+    else:
+        print(f"Unknown command: {command}")
+        print(f"Available: {', '.join(COMMAND_MAP.keys())}, bulk")
+        sys.exit(1)
+
+    print(json.dumps(result, indent=2))
+
+
+if __name__ == "__main__":
+    main()

package/extensions/skills/optional/research/drug-discovery/SKILL.md

@@ -0,0 +1,218 @@
+---
+name: drug-discovery
+description: >
+  药物发现工作流的药物研究助手。在 ChEMBL 上搜索生物活性化合物，计算类药性（Lipinski Ro5、QED、TPSA、合成可及性），通过 OpenFDA 查找药物相互作用，解读 ADMET 属性，并协助先导化合物优化。用于药物化学问题、分子属性分析、临床药理学和开放科学药物研究。
+platforms: [linux, macos, windows]
+version: 1.0.0
+author: bennytimz
+license: MIT
+metadata:
+  hermes:
+    tags: [science, chemistry, pharmacology, research, health]
+prerequisites:
+  commands: [curl, python3]
+---
+
+# 药物发现与药学研究
+
+您是一位具备药物发现、化学信息学和临床药理学深厚知识的资深药学家和药物化学家。请将此技能用于所有药学/化学研究任务。
+
+## 核心工作流
+
+### 1 — 生物活性化合物搜索 (ChEMBL)
+
+按靶点、活性或分子名称在 ChEMBL（世界上最大的开放生物活性数据库）中搜索化合物。无需 API key。
+
+```bash
+# Search compounds by target name (e.g. "EGFR", "COX-2", "ACE")
+TARGET="$1"
+ENCODED=$(python3 -c "import urllib.parse,sys; print(urllib.parse.quote(sys.argv[1]))" "$TARGET")
+curl -s "https://www.ebi.ac.uk/chembl/api/data/target/search?q=${ENCODED}&format=json" \
+  | python3 -c "
+import json,sys
+data=json.load(sys.stdin)
+targets=data.get('targets',[])[:5]
+for t in targets:
+    print(f\"ChEMBL ID : {t.get('target_chembl_id')}\")
+    print(f\"Name      : {t.get('pref_name')}\")
+    print(f\"Type      : {t.get('target_type')}\")
+    print()
+"
+```
+
+```bash
+# Get bioactivity data for a ChEMBL target ID
+TARGET_ID="$1"   # e.g. CHEMBL203
+curl -s "https://www.ebi.ac.uk/chembl/api/data/activity?target_chembl_id=${TARGET_ID}&pchembl_value__gte=6&limit=10&format=json" \
+  | python3 -c "
+import json,sys
+data=json.load(sys.stdin)
+acts=data.get('activities',[])
+print(f'Found {len(acts)} activities (pChEMBL >= 6):')
+for a in acts:
+    print(f\"  Molecule: {a.get('molecule_chembl_id')}  |  {a.get('standard_type')}: {a.get('standard_value')} {a.get('standard_units')}  |  pChEMBL: {a.get('pchembl_value')}\")
+"
+```
+
+```bash
+# Look up a specific molecule by ChEMBL ID
+MOL_ID="$1"   # e.g. CHEMBL25 (aspirin)
+curl -s "https://www.ebi.ac.uk/chembl/api/data/molecule/${MOL_ID}?format=json" \
+  | python3 -c "
+import json,sys
+m=json.load(sys.stdin)
+props=m.get('molecule_properties',{}) or {}
+print(f\"Name       : {m.get('pref_name','N/A')}\")
+print(f\"SMILES     : {m.get('molecule_structures',{}).get('canonical_smiles','N/A') if m.get('molecule_structures') else 'N/A'}\")
+print(f\"MW         : {props.get('full_mwt','N/A')} Da\")
+print(f\"LogP       : {props.get('alogp','N/A')}\")
+print(f\"HBD        : {props.get('hbd','N/A')}\")
+print(f\"HBA        : {props.get('hba','N/A')}\")
+print(f\"TPSA       : {props.get('psa','N/A')} Ų\")
+print(f\"Ro5 violations: {props.get('num_ro5_violations','N/A')}\")
+print(f\"QED        : {props.get('qed_weighted','N/A')}\")
+"
+```
+
+### 2 — 类药性计算（Lipinski Ro5 + Veber）
+
+使用 PubChem 的免费属性 API 评估任何分子是否符合公认的口服生物利用度规则 —— 无需安装 RDKit。
+
+```bash
+COMPOUND="$1"
+ENCODED=$(python3 -c "import urllib.parse,sys; print(urllib.parse.quote(sys.argv[1]))" "$COMPOUND")
+curl -s "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/name/${ENCODED}/property/MolecularWeight,XLogP,HBondDonorCount,HBondAcceptorCount,RotatableBondCount,TPSA,InChIKey/JSON" \
+  | python3 -c "
+import json,sys
+data=json.load(sys.stdin)
+props=data['PropertyTable']['Properties'][0]
+mw   = float(props.get('MolecularWeight', 0))
+logp = float(props.get('XLogP', 0))
+hbd  = int(props.get('HBondDonorCount', 0))
+hba  = int(props.get('HBondAcceptorCount', 0))
+rot  = int(props.get('RotatableBondCount', 0))
+tpsa = float(props.get('TPSA', 0))
+print('=== Lipinski Rule of Five (Ro5) ===')
+print(f'  MW   {mw:.1f} Da    {\"✓\" if mw<=500 else \"✗ VIOLATION (>500)\"}')
+print(f'  LogP {logp:.2f}       {\"✓\" if logp<=5 else \"✗ VIOLATION (>5)\"}')
+print(f'  HBD  {hbd}           {\"✓\" if hbd<=5 else \"✗ VIOLATION (>5)\"}')
+print(f'  HBA  {hba}           {\"✓\" if hba<=10 else \"✗ VIOLATION (>10)\"}')
+viol = sum([mw>500, logp>5, hbd>5, hba>10])
+print(f'  Violations: {viol}/4  {\"→ Likely orally bioavailable\" if viol<=1 else \"→ Poor oral bioavailability predicted\"}')
+print()
+print('=== Veber Oral Bioavailability Rules ===')
+print(f'  TPSA         {tpsa:.1f} Ų   {\"✓\" if tpsa<=140 else \"✗ VIOLATION (>140)\"}')
+print(f'  Rot. bonds   {rot}           {\"✓\" if rot<=10 else \"✗ VIOLATION (>10)\"}')
+print(f'  Both rules met: {\"Yes → good oral absorption predicted\" if tpsa<=140 and rot<=10 else \"No → reduced oral absorption\"}')
+"
+```
+
+### 3 — 药物相互作用与安全性查询 (OpenFDA)
+
+```bash
+DRUG="$1"
+ENCODED=$(python3 -c "import urllib.parse,sys; print(urllib.parse.quote(sys.argv[1]))" "$DRUG")
+curl -s "https://api.fda.gov/drug/label.json?search=drug_interactions:\"${ENCODED}\"&limit=3" \
+  | python3 -c "
+import json,sys
+data=json.load(sys.stdin)
+results=data.get('results',[])
+if not results:
+    print('No interaction data found in FDA labels.')
+    sys.exit()
+for r in results[:2]:
+    brand=r.get('openfda',{}).get('brand_name',['Unknown'])[0]
+    generic=r.get('openfda',{}).get('generic_name',['Unknown'])[0]
+    interactions=r.get('drug_interactions',['N/A'])[0]
+    print(f'--- {brand} ({generic}) ---')
+    print(interactions[:800])
+    print()
+"
+```
+
+```bash
+DRUG="$1"
+ENCODED=$(python3 -c "import urllib.parse,sys; print(urllib.parse.quote(sys.argv[1]))" "$DRUG")
+curl -s "https://api.fda.gov/drug/event.json?search=patient.drug.medicinalproduct:\"${ENCODED}\"&count=patient.reaction.reactionmeddrapt.exact&limit=10" \
+  | python3 -c "
+import json,sys
+data=json.load(sys.stdin)
+results=data.get('results',[])
+if not results:
+    print('No adverse event data found.')
+    sys.exit()
+print(f'Top adverse events reported:')
+for r in results[:10]:
+    print(f\"  {r['count']:>5}x  {r['term']}\")
+"
+```
+
+### 4 — PubChem 化合物搜索
+
+```bash
+COMPOUND="$1"
+ENCODED=$(python3 -c "import urllib.parse,sys; print(urllib.parse.quote(sys.argv[1]))" "$COMPOUND")
+CID=$(curl -s "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/name/${ENCODED}/cids/TXT" | head -1 | tr -d '[:space:]')
+echo "PubChem CID: $CID"
+curl -s "https://pubchem.ncbi.nlm.nih.gov/rest/pug/compound/cid/${CID}/property/IsomericSMILES,InChIKey,IUPACName/JSON" \
+  | python3 -c "
+import json,sys
+p=json.load(sys.stdin)['PropertyTable']['Properties'][0]
+print(f\"IUPAC Name : {p.get('IUPACName','N/A')}\")
+print(f\"SMILES     : {p.get('IsomericSMILES','N/A')}\")
+print(f\"InChIKey   : {p.get('InChIKey','N/A')}\")
+"
+```
+
+### 5 — 靶点与疾病文献 (OpenTargets)
+
+```bash
+GENE="$1"
+curl -s -X POST "https://api.platform.opentargets.org/api/v4/graphql" \
+  -H "Content-Type: application/json" \
+  -d "{\"query\":\"{ search(queryString: \\\"${GENE}\\\", entityNames: [\\\"target\\\"], page: {index: 0, size: 1}) { hits { id score object { ... on Target { id approvedSymbol approvedName associatedDiseases(page: {index: 0, size: 5}) { count rows { score disease { id name } } } } } } } }\"}" \
+  | python3 -c "
+import json,sys
+data=json.load(sys.stdin)
+hits=data.get('data',{}).get('search',{}).get('hits',[])
+if not hits:
+    print('Target not found.')
+    sys.exit()
+obj=hits[0]['object']
+print(f\"Target: {obj.get('approvedSymbol')} — {obj.get('approvedName')}\")
+assoc=obj.get('associatedDiseases',{})
+print(f\"Associated with {assoc.get('count',0)} diseases. Top associations:\")
+for row in assoc.get('rows',[]):
+    print(f\"  Score {row['score']:.3f}  |  {row['disease']['name']}\")
+"
+```
+
+## 推理指南
+
+在分析类药性或分子属性时，请务必：
+
+1. **首先列出原始值** —— MW、LogP、HBD、HBA、TPSA、RotBonds
+2. **应用规则集** —— Ro5 (Lipinski)、Veber、Ghose filter（视情况而定）
+3. **标记潜在风险** —— 代谢热点、hERG 风险、影响中枢神经系统（CNS）穿透的高 TPSA
+4. **建议优化方案** —— 生物电子等排体替换、前药策略、环裂解
+5. **引用来源 API** —— ChEMBL、PubChem、OpenFDA 或 OpenTargets
+
+对于 ADMET 问题，请系统性地推演吸收（Absorption）、分布（Distribution）、代谢（Metabolism）、排泄（Excretion）和毒性（Toxicity）。详细指导请参阅 references/ADMET_REFERENCE.md。
+
+## 重要提示
+
+- 所有 API 均为免费公开，无需身份验证
+- ChEMBL 频率限制：在批量请求之间添加 `sleep 1`
+- FDA 数据反映的是报告的不良事件，不一定是因果关系
+- 对于临床决策，始终建议咨询持有执照的药剂师或医生
+
+## 快速参考
+
+| 任务 | API | 端点 |
+| ------ | ----- | ---------- |
+| 寻找靶点 | ChEMBL | `/api/data/target/search?q=` |
+| 获取生物活性 | ChEMBL | `/api/data/activity?target_chembl_id=` |
+| 分子属性 | PubChem | `/rest/pug/compound/name/{name}/property/` |
+| 药物相互作用 | OpenFDA | `/drug/label.json?search=drug_interactions:` |
+| 不良事件 | OpenFDA | `/drug/event.json?search=...&count=reaction` |
+| 基因-疾病 | OpenTargets | GraphQL POST `/api/v4/graphql` |

package/extensions/skills/optional/research/drug-discovery/references/ADMET_REFERENCE.md

@@ -0,0 +1,66 @@
+# ADMET 参考指南
+
+药物发现中吸收、分布、代谢、排泄和毒性 (ADMET) 分析的综合参考。
+
+## 类药性规则集
+
+### Lipinski 五规则 (Ro5)
+
+| 属性 | 阈值 |
+| ---------- | ----------- |
+| 分子量 (MW) | ≤ 500 Da |
+| 亲脂性 (LogP) | ≤ 5 |
+| 氢键供体 (HBD) | ≤ 5 |
+| 氢键受体 (HBA) | ≤ 10 |
+
+参考文献：Lipinski et al., Adv. Drug Deliv. Rev. 23, 3–25 (1997)。
+
+### Veber 口服生物利用度规则
+
+| 属性 | 阈值 |
+| ---------- | ----------- |
+| TPSA | ≤ 140 Ų |
+| 可旋转键 | ≤ 10 |
+
+参考文献：Veber et al., J. Med. Chem. 45, 2615–2623 (2002)。
+
+### 中枢神经系统穿透性 (BBB)
+
+| 属性 | CNS 理想范围 |
+| ---------- | ------------- |
+| MW | ≤ 400 Da |
+| LogP | 1–3 |
+| TPSA | < 90 Ų |
+| HBD | ≤ 3 |
+
+## CYP450 代谢
+
+| 亚型 | 药物百分比 | 知名抑制剂 |
+| --------- | --------- | ------------------- |
+| CYP3A4 | ~50% | 葡萄柚，酮康唑 |
+| CYP2D6 | ~25% | 氟西汀，帕罗西汀 |
+| CYP2C9 | ~15% | 氟康唑，胺碘酮 |
+| CYP2C19 | ~10% | 奥美拉唑，氟西汀 |
+| CYP1A2 | ~5% | 氟伏沙明，环丙沙星 |
+
+## hERG 心脏毒性风险
+
+结构警报：碱性氮 (pKa 7–9) + 芳香环 + 疏水部分，LogP > 3.5 + 碱性胺。
+
+缓解策略：降低碱性，引入极性基团，破坏平面结构。
+
+## 常见生物电子等排体替换
+
+| 原始基团 | 生物电子等排体 | 目的 |
+| ---------- | ------------- | --------- |
+| -COOH | -tetrazole, -SO₂NH₂ | 提高渗透性 |
+| -OH (酚类) | -F, -CN | 减少葡萄糖醛酸化 |
+| 苯基 | 吡啶，噻吩 | 降低 LogP |
+| 酯 | -CONHR | 减少水解 |
+
+## 关键 API
+
+- ChEMBL: https://www.ebi.ac.uk/chembl/api/data/
+- PubChem: https://pubchem.ncbi.nlm.nih.gov/rest/pug/
+- OpenFDA: https://api.fda.gov/drug/
+- OpenTargets GraphQL: https://api.platform.opentargets.org/api/v4/graphql