A novel amide alkaloid,bursatamide A(1),featuring an unprecedented propyl-hexahydronaphthalene carbon frame-work,was isolated from the infrequently studied sea hare Bursatella leachi,alongside a new 3-phenoxypropanenitrile alkaloid,bursatellin B(2),and twelve known compounds.The structures of 1 and 2 were elucidated through comprehensive spectroscopic data analyses,while their relative and absolute configurations(ACs)were established through total synthesis and a series of quantum chem-ical calculations,including calculated electronic circular dichroism(ECD)spectra,optical rotatory dispersion(ORD)methods,and DP4+probability analyses.Bursatamide A(1)demonstrated inhibitory effects against the human pathogenic bacteria Listeria monocyt-ogenes and Vibrio cholerae.Erythro-bursatellin B(21),a diastereoisomer of 2,exhibited notable antibacterial activity against the fish pathogenic bacterium Streptococcus parauberis FP KSP28,with an MIC90 value of 0.0472 μg·mL-1.

Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC₅₀ = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.

Endosomal TLRs (TLR3/7/8/9) are highly analogous innate immunity sensors for various viral or bacterial RNA/DNA molecular patterns. Among them, TLR7, in particular, has been suggested to be a target for various inflammatory disorders and autoimmune diseases including systemic lupus erythematosus (SLE); but few small-molecule inhibitors with elaborated mechanism have been reported in literature. Here, we reported a well-characterized human TLR7-specific small-molecule inhibitor, TH-407b, with promising potency and negligible cytotoxicity through a novel binding mechanism. Notably, TH-407b not only effectively inhibited TLR7-mediated pro-inflammatory signaling in a variety of cultured cell lines but also demonstrated potent inflammation suppressing activities in primary peripheral blood mononuclear cells (PBMCs) derived from SLE patients. Furthermore, TH-407b showed prominent efficacy in vivo, improved survival rate and ameliorated symptoms of SLE model mice. To obtain molecular insights into the TH-407b derivatives' inhibition mechanism, we performed the structural analysis of TLR7/TH-407b complex using cryogenic electron microscopy (cryo-EM) method. As an atomistic resolution cryo-EM structure of the TLR family, it not only of value to facilitate structure-based drug design, but also shed light to methodology development of small proteins using EM. Significantly, TH-407b has unveiled an inhibition strategy for TLR7 via stabilizing its resting/inactivated state. Such a resting state could be generally applicable to all TLRs, rendering a useful method for targeting this group of important immunological receptors.

Aiming at the medical service robot used in the indoor environment, this study proposes a method to test the pose accuracy of its working surface based on the binocular vision system. This method uses a binocular vision coordinate system to measure targets fixed on the working surface of the service robot, aligns the measurement system with the robot base coordinate system through the nonlinear least squares method, and integrates the multi-eye image data to achieve the accuracy test of the working surface. Finally, the vision test program was tested and verified on a mobile service robot model ABIR X8. According to the accuracy index given in GB/T 38124 Service Robot Performance Test Method, the test results of its pose accuracy were obtained.
Optical Devices ; Robotics ; Vision, Binocular

Objective:This study aimed to discover the HIV infection and associated factors among male sex workers (MSW) who provide sexual services for men. Data from this study thus can be used to provide evidence for designing related intervention programs.Methods:In this observational study, MSW were recruited from May to July, 2019 in KTV venues in Wuxi, China. A questionnaire was used to collect information with blood sample collected and tested for HIV and syphilis. EpiData 3.0 and SPSS 17.0 software were used to clean up data and statistical analysis.Results:A number of 500 MSW were involved including 243 (48.6 %) heterosexual and 257 (51.4 %) homosexual MSW. The overall HIV prevalence was 5.4 %(27/500) among all the MSW. there were significant differences between the HIV prevalence rates, the heterosexual MSW (3.3 %, 8/243) and the homosexual MSW (7.4 %, 19/257)( χ2=4.112, P=0.043). In the past 3 months, 28.0 % (72/257) of the homosexual MSW mainly engaged in receptive anal sex which was higher than 11.5 %(28/243) of the heterosexual MSW. Compared to 15.6 % (40/257) of the homosexual MSW who engaged in heterosexual behavior, a higher proportion of 98.4 % (239/243) was noticed among the heterosexual MSW. Higher percentage (44.9 %, 109/243) appeared among the heterosexual MSW who had not been tested for HIV than the homosexual MSW (20.6 %, 53/257). Results from logistic regression multivariate analysis showed that age ≥30 (a OR=7.54, 95 %CI: 2.53-37.11), having unprotected anal sexual practice (a OR=3.76, 95 %CI:1.15-12.23), having anal sex after drinking alcohol (a OR=10.91, 95 %CI: 2.29-51.87) and syphilis tested positive (a OR=8.23, 95 %CI:1.29-52.51) were risk factors associated with HIV infection among the heterosexual MSW. Having unprotected anal sexual behavior (a OR=2.94, 95 %CI: 1.17-7.37), having group anal sex (a OR=4.08, 95 %CI:1.05-15.81), without record on HIV testing (a OR=6.58, 95 %CI: 2.01-18.06) and syphilis tested positive (a OR=4.55, 95 %CI: 1.15-18.06) were risk factors associated with HIV among the homosexual MSW. Conclusions:High HIV prevalence was discovered among both heterosexual and homosexual MSW in Wuxi, China. Differences in sexual behaviors between these two groups should be considered when designing targeted HIV intervention programs for these populations.

Objective To compare the clinical outcomes between open reduction and fixation with cannulated screws via the modified Burks-Schaffer approach versus arthroscopic EndoButton plating for avulsion fracture of the tibial attachment of the posterior cruciate ligament(PCL).Methods From February 2013 to August 2017,41 patients with acute displaced avulsion fracture of the tibial PCL attachment were treated operatively at Department of Trauma Surgery,The Affiliated Hospital to Qingdao University.They were 24 men and 17 women,aged from 18 to 65 years (average,39 years).The lefi knee was injured in 22cases and the right knee in 19.They were divided into 2 groups according to their different fixation methods.The open reduction and fixation group (23 cases) received open reduction and fixation with cannulated screws via the modified Burks-Schaffer approach while the arthroscopic group (18 cases) arthroscopic Endobutton plating.The 2 groups were compared in terms of operation time,bleeding,objective knee scores and knee range of motion (ROM) after operation.Results All the 41 patients were followed up from 23 to 40months (average,27.2 months).Their follow-up revealed no incision infection,malunion,nonunion or loosening of the implants.Their knee X-ray films at the final follow-ups showed bony union of all the avulsion fractures.There were significant differences between the open reduction and fixation group and the arthroscopic group in operation time (52.6±7.3 min versus 86.8±9.2 min) and bleeding (63.9±12.7 mL versus 19.7 ± 10.2 mL) (P ＜ 0.05).There was no significant difference in the objective knee scores or knee ROM between the 2 groups (P ＞ 0.05).Conclusions Both open reduction and cannulated screw fixation via the modified Burks-Schaffer approach and arthroscopic EndoButton plating can achieve satisfactory clinical outcomes in the treatment of avulsion fracture of the tibial PCL attachment.Although the 2 methods make no significant differences in stability of the knee joint or in clinical scores,the latter leads to less bleeding and the former shorter operation time.

OBJECTIVE： To establish a method for simultaneous determination of α-pinene， β-pinene， limonene and α-terpineol in volatile oil of Forsythia suspensa. METHODS： GC method was adopted. The determination was performed on HP-5 capillary column through temperature-programmed route. The inlet temperature was 230 ℃， and detector temperature was 250 ℃； split sampling was applied （split ratio of 8 ∶ 1）； the air flow rate was 300 mL/min， the hydrogen flow rate was 30   mL/min， the tail gas flow rate was 30 mL/min， and the injection volume was 1 μL. Using limonene as internal reference， relative correction factors of α-pinene， β-pinene and α-terpineol were established， and the reproducibility of relative correction factors were investigated by using different chromatographs and columns， and chromatographic peak location of components was measured. The contents of above components were calculated with QAMS， and then compared with the results of external standard method. RESULTS： The linear range of α-pinene， β-pinene， limonene and α-terpineol were 16.5-990.0， 38.1-2 287.5， 8.2-491.2， 2.4-142.5  μg/mL， respectively （r≥0.999 1）. RSDs of precision， reproducibility and stability tests were all lower than 3％ （n＝6）. Average recoveries were 99.7％-105.5％（RSD＜4％，n＝9）. Compared with limonene （1.00），the average relative correction factors of α-pinene， β-pinene and α-terpineol were 0.91，0.86 and 1.11（n＝3）； relative retention time were 0.69-0.74， 0.81-0.86， 1.25-1.35（RSD＜3％，n＝3）. By using different chromatographs and columns， RSDs of relative correction factors were 0.21％-4.65％（n＝6）. Compared with external standard method， determination results of above 4 components were consistent （the absolute value of relative error were all less than 7％）. CONCLUSIONS： QAMS can be used for simultaneous determination of 4 kinds of effective components in volatile oil from F. suspensa.

Based on gram positive enhancer matrix displaying technology, we designed and evaluated a bacteria-like particle vaccine against swine type O Foot-and-mouth disease virus. Three optimized genes of type O Foot-and-mouth disease virus strain Mya98 were cloned into recombinant prokaryotic expression vector pQZ-PA and renamed as pQZ-BT1B-PA, pQZ-BT2B-PA and pQZ-B (T1BT2) 4B-PA, fused with an anchor protein (PA) binding to Gram-positive enhancer matrix (GEM) particles specifically. The protein expression was identified with SDS-PAGE and Western blotting, and then purified with GEM particles. Five-week old female mice were randomly divided into six groups and all the immunization was developed according to subcutaneous injection. Mice in the first three groups were injected with 50 μg/dose GEM-BT1B, GEM-BT2B and GEM-B (T1BT2) 4B, respectively. Mice in the fourth group were immunized with commercial peptide vaccine as positive control. The fifth group vaccinated with host E. coli transformed with pQZ-PA fulfilled as negative control. Mice in the last group injected with sterile PBS served as blank control. The humoral immunity of recombinant protein vaccine was evaluated with peptide-specific antibody and LPB antibody. The cellular immunity was evaluated with lymphocyte proliferation test and cytokine expression detection. SDS-PAGE and Western blotting showed that the most part of soluble target fusion protein have been purified and displayed on GEM particles. Vaccine GEM-B (T1BT2) 4B stimulated mice produce not only higher level of specific antibody against peptide and Foot-and-mouth disease virus specific liquid phase blocking antibody, but also more vigorous spleen lymph proliferation and higher levels of Th1 type cytokines. To summarize, vaccine of GEM-B (T1BT2) 4B possessed good immunogenicity and opened a new way for further Foot-and-mouth disease virus subunit vaccine design.

Objective To investigate th grade of CT in colonic diverticulitis and the value in predicting clinical treatment.Methods CT data of totally 41 patients with colonic diverticulitis were analyzed retrospectively.According to the imaging signs,the grading of diverticulitis cases was performed.Patients with level 1 to 3 were considered as only need non-operative treatment,those with level 4 or 5 were considered as need surgical treatment.The consistency of predictive treatment plans were contrasted with clinical practical treatment results.Results The CT features of colonic diverticulitis were saclike protrusions bulged outside of the bowel wall with colon wall thickening in 40 cases (40/41,97.56％) and fuzzy pericolonal fat space in 39 cases (39/41,97.12％).The diagnostic accuracy of preoperative CT grading in predictive treatment plan was 85.37 ％ (36/41).Conclusion Colonic diverticulitis have certain characteristic CT findings.CT grading of diverticulitis is helpful to formulate appropriate clinical treatment.

OBJECTIVE:To establish a method for the determination of ethanol,acetonitrile,dichloromethane,ethyl acetate, pyridine in vidarabine monophosphate. METHODS:Headspace GC was performed on the column of Agilent DB-624,programmed temperature,inlet temperature was 200 ℃,the detector was flame ionization detector,detecting temperature was 250 ℃,nitrogen was carrier gas,flow rate was 3 ml/min,split ratio was 1∶1,the top bottles equilibrium temperature was 100 ℃,and equilibrium time was 45 min,injection volume was 1 ml. external standard was used for quantitative analysis. RESULTS:The peaks of five re-sidual solvents could be completely separated from the other peaks respectively,The linear rang was 24.7-296.3 μg/ml for ethanol (r=0.999 6)、1.9-23.2 μg/ml for acetonitrile(r=0.999 0),2.8-33.6 μg/ml for dichloromethane(r=0.998 0),24.7-295.9 μg/ml for ethyl acetate(r=0.999 5),1.0-11.9 μg/ml for pyridine(r=0.998 6);RSDs of precision and reproducibility tests were lower than 4.35%;recoveries were 102.4%(RSD=2.0%,n=9)、102.1%(RSD=3.4%,n=9)、105.5%(RSD=4.8%,n=9)、100.3%(RSD=4.8%, n=9)、98.3%(RSD=4.0%,n=9). The minimum quantifation limit was 0.304 4-0.988 0 μg/ml and the minimum detection limit was 0.101 5-0.329 3 μg/ml. CONCLUSIONS:The method is simple,accurate and reproducible,and can be used for the determination of residual solvents in vidarabine monophosphate.