Fifty whitespotted bamboo sharks (Chiloscyllium playgiosum) of both sexes were used to establish a large capacity variable domain of the new antigen receptor (VNAR) library with a total capacity of over 10⁹ colony-forming units (CFU). It was applied to screen VNARs against human serum albumin (HSA) and human transcription factor EB (TFEB), respectively. Meanwhile, VNAR libraries specific to HSA and TFEB with capacities above 10⁸ CFU were obtained following conventional immunization. These two approaches were systematically studied in terms of VNAR yield and composition. By comparing the VNAR sequences obtained from naïve and antigen-immunized libraries, we found that the complementary-determining region 3 (CDR3) of the former differs in composition from that of the latter. It shares a higher degree of homology with the naïve library. Meanwhile, the binding efficiency assessed by ELISA is also different between the naïve and antigen-immunized libraries. The binding of VNARs from the TFEB-immunized library appeared to surpass that observed with the naïve libraries, whereas the performance of VNARs from the HSA-immunized library indicated that both the immunized and naïve libraries for HSA had positive binding responses in polyclonal and monoclonal ELISA. The results are useful to develop novel diagnostic and therapeutic products based on shark VNARs.

Filamenting temperature-sensitive mutant Z (FtsZ), a protein essential for bacterial cell division, is highly conserved across bacterial species but absent in humans, positioning it as a strategic target for the development of antibiotics. Significant efforts to identify FtsZ inhibitors-via biochemical assays (e.g., GTPase activity) and cellular approaches (e.g., immunofluorescence)-have yielded over 100 natural products and synthetic compounds, whose cheminformatics clustering underscores a limited chemical diversity among the current scaffolds. Structural studies, including X-ray crystallography and cryo-electron microscopy, have resolved 97 FtsZ structures revealing conserved polymerization mechanisms and conformational plasticity, as exemplified by extremophile adaptations (e.g., Shewanella benthica from the high-pressure environment of the Mariana Trench's Challenger Deep). However, clinical translation is hindered by weak binding affinities, inhibitory inefficacy, dynamic conformational flexibility, and evolving drug resistance linked to FtsZ's functional plasticity. To address these challenges, future efforts should be directed to resolve transient assembly intermediates, leveraging machine learning with high-throughput screening, and integrating structural biology with pharmacokinetic optimization. Multidisciplinary strategies combining these approaches hold promise for translating FtsZ-focused research into clinically viable therapies, addressing the critical unmet need posed by antibiotics resistance.

Objective:To evaluate the reliability and validity of a questionnaire assessing the leadership qualities of primary healthcare institution managers, and to further clarify the current state of leadership development among management teams of community health service centers in Shanghai.Methods:The study was a cross-sectional survey. It was conducted from August to December 2021, and used a stratified sampling method. Using a self-developed questionnaire for primary healthcare institution managers, we surveyed 279 individuals from 10 community health service centers in Shanghai, including management teams, middle-level cadres, general practitioners, and staff from health administrative departments in their respective districts. Leadership qualities were evaluated on five dimensions: inspiration, decisiveness, control, influence, and foresight. Cronbach′s α coefficient and split half coefficient were used to analyze the reliability of the questionnaire, and confirmatory factor analysis was used to assess the structural validity of the scale.Results:The overall Cronbach′s α reliability of the questionnaire for the comprehensive management of community health service centers was 0.96, and the Spearman-Brown split-half coefficient was 0.94. The validity analysis yielded a KMO value of 0.975, the RMSEA for factor analysis was 0.085, and the adaptation indexes all met the model adaptation conditions. Of the 279 participants, 174 were female (62.4%), 257 held a mid-level or higher professional title (92.1%). The overall leadership score of the community health service center management teams was (4.43±0.59), with the dimensions ranked from highest to lowest as follows: inspiration (4.52±0.55), decisiveness (4.46±0.62), control (4.44±0.60), influence (4.42±0.63), and foresight (4.32±0.69). The foresight score was significantly lower than the other four dimensions (all P<0.05). Conclusions:The questionnaire used to assess the leadership qualities of primary healthcare institution managers is reliable and valid. The development of leadership qualities among management teams of community health service centers in Shanghai is unbalanced, with foresight being the weakest dimension.

Objective:To calibrate the absorbed doses of the configured ray water with different gears of energies in accelerator based onof International Atomic Energy Agency(IAEA)277 and 381 reports,so as to ensure the accuracy of the output dose of the linear accelerator during clinical radiotherapy.Methods:Elekta Infinity linear accelerator was used in this study,and the photon beam energies were respectively 6MV flattening filter(FF)mode and 6MV flattening filter free(FFF)mode.The electron beam energies were respectively 4,6,8,10,12 and 15MeV.According to the IAEA TRS277 and TRS381 reports,the calibrations of output doses in photon and electron beam waters were performed respectively by using the PTW dosimeter,PTW30013 finger type of ionization chamber and PTW34001 parallel plate ionization chamber.The error of each step was analyzed,and the accuracies of the calibrations of using different standards for the output waters of linear accelerator were compared.Results:The output amounts of photon beams of FF mode and FFF mode of 6MV at the maximum dose point in water were respectively 1.003 and 1.008cGy/MU.The output amounts of the energy of each gear of electron beams of 4,6,8,10,12 and 15MeV at the maximum dose point in water were respectively 1.003,1.002,0.998,0.999,1.000 and 1.003 cGy/MU.The calibration of the output of each gear of energy rays at the maximum dose point in water was 1cCy corresponded to 1MU,which error was less than 1%.Conclusion:The calibration for the output dose amount of accelerator in water on the basis of IAEA TRS277 and trs381 can ensure the accuracy of the output dose of the accelerator.

Seven novel linear polyketides,talaketides A-G(1-7),were isolated from the rice media cultures of the mangrove sed-iment-derived fungus Talaromyces sp.SCSIO 41027.Among these,talaketides A-E(1-5)represented unprecedented unsaturated lin-ear polyketides with an epoxy ring structure.The structures,including absolute configurations of these compounds,were elucidated through detailed analyses of nuclear magnetic resonance(NMR)and high-resolution mass spectrometry(HR-MS)data,as well as elec-tronic custom distributors(ECD)calculations.In the cytotoxicity screening against prostate cancer cell lines,talaketide E(5)demon-strated a dose-dependent inhibitory effect on prostate cancer PC-3 cell lines,with an IC50 value of 14.44 μmol·L-1.Moreover,com-pound 5 significantly inhibited the cloning formation of PC-3 cell lines and arrested the cell cycle in S-phase,ultimately inducing ap-optosis.These findings indicate that compound 5 may serve as a promising lead compound for the development of a potential treat-ment for prostate cancer.

Objective:To compare the efficacy of endoscopic submucosal dissection (ESD) and modified-endoscopic mucosal resection (M-EMR) for G1 rectal neuroendocrine tumors (RNETs) .Methods:Data of 121 patients with pathologically confirmed G1 RNETs treated with ESD ( n=105) or M-EMR ( n=16) in Nanjing Drum Tower Hospital from January 2017 to September 2020 were retrospectively analyzed. The complete resection rate, complication incidence, hospital stay, treatment cost and other indicators of the two groups were compared by using inverse probability of treatment weighting (IPTW). Results:There were significant differences in tumor number ( χ2=8.76, P=0.003), tumor invasion depth ( χ2=6.96, P=0.008), utilization of metal clips [82.9% (87/105) VS 93.8% (15/16), χ2=8.78, P=0.003], number of metal clips ( χ2=8.41, P=0.016), hemostasis using hot clamp [78.1% (82/105) VS 18.7% (3/16), χ2=20.64, P<0.001], traction procedure [2.9% (3/105) VS 18.7% (3/16), χ2=4.45, P=0.035] and treatment cost (17 568.6 ± 8 911.0 yuan VS 8 120.8±1 528.2 yuan, t=3.65, P<0.001) between the ESD group and the M-EMR group. After verifying the stability of the results using IPTW sensitivity analysis, there was still significant difference in the treatment cost ( t=2.07, P<0.001). Conclusion:Both ESD and M-EMR demonstrate comparable efficacy in treating G1 RNETs; however, M-EMR exhibites lower treatment costs.

Objective:To explore the factors associated with vascular luminal dilatational remodeling (VLDR) following balloon angioplasty for intracranial atherosclerotic stenosis (ICAS).Methods:A case-control study was conducted to analyze the data of symptomatic severe ICAS patients who received either paclitaxel-coated balloon angioplasty (PCBA) or plain balloon angioplasty (POBA) at our center from January 2019 to January 2022 and completed the six-month follow-up. The patients were divided into VLDR group and non-VLDR group according to whether VLDR occurred on follow-up digital subtraction angiography (DSA). The baseline data, preoperative and postoperative lesion characteristics (DSA), and perioperative related information were collected. The definition of VLDR was a decrease in luminal stenosis rate by more than 10% at the time of follow-up compared to the immediate postoperative period. Multivariate logistic regression was performed to analyze possible factors affecting VLDR such as balloon type, balloon length, and expansion time.Results:A total of 88 patients were included in this study, with 16 in the VLDR group and 72 in the non-VLDR group. The follow-up time for all included patients was 6.00 (5.00, 7.00) months. VLDR occurred in 18.2% (16/88) of cases, with a VLDR incidence of 30.4% (14/46) after PCBA and 4.8% (2/42) after POBA. Univariate logistic regression analysis revealed that treatment balloon type, balloon length, inflated time, immediate postoperative stenosis rate, follow-up time and Mori classification may affect the occurrence of VLDR. Multivariate logistic regression analysis showed that the use of paclitaxel-coated balloon (PCB) ( OR=9.82, 95% CI 1.99-48.49, P=0.005) and postoperative immediate stenosis rate ( OR=1.07, 95% CI 1.00-1.14, P=0.042) were independently associated with VLDR. Conclusion:The occurrence of VLDR following balloon angioplasty in ICAS was associated with the use of PCB and immediate postoperative stenosis rates, which will provide guidance for the clinical application of PCB.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Objective:To investigate the feasibility and effectiveness of incision subcutaneous porous catheter combined with ropivacaine analgesia in enhanced recovery after laparoscopic gastrointestinal surgery.Methods:The clinical data of 140 patients underwent gastrointestinal surgery from August 2021 to April 2022 in Shanghai Fourth People′s Hospital, School of Medicine, Tongji University were retrospectively analyzed. Among them, 70 patients were given routine postoperative analgesia (control group), and 70 patients were given incision subcutaneous porous catheter combined with ropivacaine analgesia on the basis of routine postoperative analgesia (observation group). The visual analogue score (VAS) 4, 24, 32, 48, 56 and 72 h after operation was evaluated; and the complications of subcutaneous catheterization, incision infection, postoperative nausea vomiting, neurological symptoms, time to extubation, patient satisfaction degree, recovery time of intestinal function and hospital stay were recorded.Results:The VAS 4, 24, 32, 48, 56 and 72 h after operation in observation group was significantly lower than that in control group: 1.000 (- 0.250, 2.250) scores vs. 1.000 (- 1.000, 3.000) scores, 2.000 (1.000, 3.000) scores vs. 4.000 (2.000, 6.000) scores, 1.000 (0.000, 2.000) scores vs. 3.000 (1.000, 5.000) scores, 2.000 (1.000, 3.000) scores vs. 3.000 (1.750, 4.250) scores, (1.100 ± 0.934) scores vs. (2.085 ± 0.943) scores and (0.985 ± 0.842) scores vs. (1.814 ± 0.921) scores, and there was statistical difference ( P<0.05 or <0.01). The recovery time of intestinal function and hospital stay in observation group were significantly shorter than that that in control group: (1.743 ± 0.557) d vs. (2.200 ± 0.714) d and (8.043 ± 1.160) d vs. (8.757 ± 1.221) d, and there were statistical difference ( P<0.01); there were no statistical differences in the rate of incision infection, incidence of postoperative nausea vomiting, time to extubation and patient dissatisfaction rate between two groups ( P>0.05); there were no the complications of subcutaneous catheterization and neurological symptoms in two groups. Conclusions:The incision subcutaneous porous catheter combined with ropivacaine analgesia after laparoscopic gastrointestinal surgery is a safe, effective and feasible method. Multimodal analgesia under enhanced recovery after surgery can increase the postoperative recovery after gastrointestinal operations and shorten the postoperative hospital stay.