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Context: Individuals with Li-Fraumeni syndrome (LFS) have an inherited cancer predisposition to a diverse array of malignancies beginning early in life; survivors of one cancer have a markedly elevated risk of additional primary tumors. The underlying genetic defect in the majority of the families is a germline mutation in the TP53 tumor suppressor gene. The diversity of tumors and rarity of families have contributed to the difficulty in devising effective screening recommendations for members of LFS kindreds.Objective: To gather preliminary data with which to evaluate F18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging as a potential surveillance modality to detect early malignancies in asymptomatic members of LFS kindreds.Design, Setting, and Participants: Members of LFS families with documented germline TP53 mutations or obligate carrier status, no history of cancer within 5 years of enrollment, and no symptoms of cancer or ill-health were offered FDG-PET/CT scanning as a screening test in a comprehensive US cancer center from 2006 to 2007. Scans were initially reviewed clinically, then centrally reviewed by an expert radiologist.Main Outcome Measure: The primary outcome was the detection of new primary cancers using FDG-PET/CT scanning.Results: Of 15 individuals, baseline FDG-PET/CT scan identified asymptomatic cancers in 3 (20%). Two individuals had papillary thyroid cancers (stage II and stage III) and one individual had stage II esophageal adenocarcinoma.Conclusions: These preliminary data provide the first evidence for a potential cancer surveillance strategy that may be worthy of further investigation for patients with LFS. Concerns about radiation exposure and other challenges inherent in screening high-risk patients will require further consideration. [ABSTRACT FROM AUTHOR]

A comprehensive mutational scanning test for the p53 coding region based on multiplex PCR and two-dimensional DNA electrophoresis was designed and evaluated. In a 2-step multiplex PCR, the p53 coding region (exons 2-11) was amplified as a single 8646-bp fragment by long-distance PCR in step one. This fragment served as a template for the subsequent co-amplification of the individual exons in two multiplex groups in step two. The multiplex products were then separated, first on the basis of size in non-denaturant polyacrylamide gels and then on the basis of sequence by denaturing gradient gel electrophoresis (DGGE). Primers for optimal PCR, melting behavior and 2-D gel distribution were designed using a recently developed computer program. The resulting two-dimensional gene scanning (TDGS) test was evaluated by screening, in a blinded fashion, 29 coded DNA samples from Li-Fraumeni syndrome patients with previously identified germline mutations. All mutations were correctly detected. This assay provides an accurate, cost-effective and non-radioactive method for simultaneous mutational scanning of all p53 coding exons. [ABSTRACT FROM PUBLISHER]

Background: Allergen testing has emerged as a pivotal component in prevention and treatment strategies for allergic diseases among children and the utilization of specific IgE (sIgE) through a fully automated chemiluminescent microarray immunoassay (CLMIA) has emerged as a promising trend in the simultaneous detection of multiple allergenic components of children., Methods: The accuracy and reliability of CLMIA were verified using children's serum samples that concentrated on allergens. the allergens. The clinical diagnostic practicability of CLMIA was assessed through comprehensive evaluations including measurements of the limit of detection (LOD), intra-batch, and inter-batch precision, linearity analysis, the cross-contamination rate, and the concordance rate with the Phadia system., Results: After the optimization process of CLMIA, the LODs for allergens were calculated to be below 0.01 kU/L, demonstrating the high sensitivity of CLMIA. All components exhibited good linearity within the range of 0.1-100.0 kU/L and the coefficient of determinations (R 2  > 0.99). The data of intra-batch precision (<10 %) and inter-batch data (<15 %) illustrated the high reproducibility of CLMIA. The cross-contamination rates for allergens (<0.5 %) showed the high accuracy of CLMIA without interfering. The positive concordance rate between CLMIA and the Phadia system exceeds 90 % with a good negative concordance rate (>85 %) and the Kappa coefficients (>0.8), suggesting the close alignment of CLMIA and the Phadia system and showing the satisfactory clinical potential of CLMIA in children's allergy disease., Conclusions: The application of CLMIA has been promising in allergen testing, especially for detecting multiple allergenic components in children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Functional redundancy is considered a pivotal mechanism for maintaining the adaptability of species by preventing the loss of key functions in response to dehydration. However, we still lack a comprehensive understanding of the redundancy of leaf hydraulic systems along aridity gradients. Here, photosynthesis (A n ), stomatal conductance (g s ) and leaf hydraulic conductance (K leaf ) during dehydration were measured in 20 woody species from a range of aridity index (AI) conditions and growing in a common garden to quantify stomatal redundancy (SR), the extent of stomatal opening beyond the optimum required for maximum photosynthesis (A max ), leaf hydraulic redundancy (HR), and the extent of leaf hydraulic conductance (K leaf ) beyond the optimum required for maximum g s (g s-max ). The findings revealed that species from arid habitats tended to have higher SRs but lower HRs than did species from humid habitats. The relatively high SR in arid species arose from relatively high g s-max values. The relatively low HR arose from the relatively high K leaf value at a 5% reduction in g s-max (K leaf-gs ). Our results suggest that greater stomatal redundancy and lower hydraulic redundancy prevent the loss of photosynthesis and water transportation, respectively, and thus might be the key adaptive mechanisms for plants to adapt to drought conditions., (© 2025 John Wiley & Sons Ltd.)

Abstract: According to the World Health Organization (WHO) manual, sperm concentration should be measured using an improved Neubauer hemocytometer, while sperm motility should be measured by manual assessment. However, in China, thousands of laboratories do not use the improved Neubauer hemocytometer or method; instead, the Makler counting chamber is one of the most widely used chambers. To study sources of error that could impact the measurement of the apparent concentration and motility of sperm using the Makler counting chamber and to verify its accuracy for clinical application, 67 semen samples from patients attending the Department of Andrology, West China Second University Hospital, Sichuan University (Chengdu, China) between 13 September 2023 and 27 September 2023, were included. Compared with applying the cover glass immediately, delaying the application of the cover glass for 5 s, 10 s, and 30 s resulted in average increases in the sperm concentration of 30.3%, 74.1%, and 107.5%, respectively (all P < 0.0001) and in the progressive motility (PR) of 17.7%, 30.8%, and 39.6%, respectively (all P < 0.0001). However, when the semen specimens were fixed with formaldehyde, a delay in the application of the cover glass for 5 s, 10 s, and 30 s resulted in an average increase in the sperm concentration of 6.7%, 10.8%, and 14.6%, respectively, compared with immediate application of the cover glass. The accumulation of motile sperm due to delays in the application of the cover glass is a significant source of error with the Makler counting chamber and should be avoided., (Copyright ©The Author(s)(2024).)

Three Tomicus bark beetles (T. yunnanensis, T. brevipilosus and T. minor) coexist in the trunks of Pinus yunnanensis but possess relatively independent spatio-temporal ecological niches. This makes them become a good case for addressing functional differentiation of chemosensory-related proteins among closely related species in odorant recognition and insecticide sequestering. In this study, we used odorant binding protein (OBP) orthologues highly expressed in antennae to illustrate this question. We first identified 33, 35 and 34 OBPs from T. yunnanensis, T. brevipilosus and T. minor, respectively, with 33 groups of OBP orthologues. Sequence and phylogenetic analyses revealed the conservation and differences of OBP orthologues across three Tomicus beetles. Expression profiles revealed that the majority of Tomicus OBPs were abundantly expressed in antennae where 11 groups of OBP orthologues shared a significantly antenna-enriched distribution. Four groups of antennal OBP orthologues (OBP2, OBP9, OBP10 and OBP16 totaling 12 genes) presented diverse ligand-binding properties, responding differently to five classes of ecologically relevant odorants as well as various insecticides. In particular, OBP orthologues were tuned differentially to host and non-host odorants, and chlorpyrifos was identified as the best ligand for 12 Tomicus OBPs. Our study thus sheds light on functional conservation and divergence of OBP orthologues among three sympatric Tomicus bark beetles, possibly as an implication for the early or late of host colonization, ecological niche differences and the strong habitat adaptation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The threats to the safety of humans and the environment and the resistance of agricultural chemicals to plant pathogenic fungi and bacteria highlight an urgent need to find safe and efficient alternatives to chemical fungicides and bactericides. In this study, a series of Berberine (BBR) derivatives were designed, synthesized and evaluated for in vitro and in vivo antimicrobial activity against plant pathogenic fungi and bacteria., Results: Bioassay results indicated that compounds A11, A14, A20, A21, A22, A25, A26, E1, E2, E3, Z1 and Z2 showed high inhibitory activity against Sclerotinia sclerotiorum and Botrytis cinerea. Especially, A25 showed a broad spectrum and the highest antifungal activity among these compounds. Its EC 50 value against Botrytis cinerea was 1.34 μg mL -1 . Compound E6 possessed high inhibitory activity against Xanthomonas oryzae and Xanthomonas Campestris, with MIC 90 values of 3.12 μg mL -1 and 1.56 μg mL -1 . A Topomer CoMFA model was generated for 3D-QSAR studies based on anti-B. cinerea effects, with high predictive accuracy, showed that the addition of an appropriate substituent group at the para-position of benzyl of BBR derivatives could effectively improve the anti-B. cinerea activity. In addition, compound A25 could significantly inhibit the spore germination of Botrytis cinerea at low concentration, and compound F4 exhibited remarkable curative and protective efficiencies on rice bacterial leaf blight., Conclusion: This study indicates that the BBR derivatives are hopeful for further exploration as the lead compound with novel antimicrobial agents. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: To analyze the association between the hemoglobin glycation index (HGI) and the long-term prognosis of patients with coronary artery disease (CAD)., Methods: HGI represented the difference between laboratory measured Hemoglobin A1c (HbA1c) and predicted HbA1c based on a liner regression between Hb1Ac and fasting plasma glucose (FPG). A total of 10 598 patients who treated with percutaneous coronary intervention (PCI) were stratified into three groups (low HGI group: HGI<-0.506, medium HGI group: -0.506 ≤ HGI < 0.179, and high HGI group: HGI ≥ 0.179). The primary endpoints includes all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs)., Results: A total of 321 ACMs, 243 CMs, 774 MACEs, and 854 MACCEs were recorded during a 60-month follow-up period. After adjusting for confounders using a multivariate Cox regression analysis, the patients in the low HGI group had a significantly increased risk of ACM (adjusted HR = 1.683, 95%CI:1.179-2.404, P = 0.004) and CM (HR = 1.604, 95%CI:1.064-2.417, P = 0.024) as compared with patients in the medium HGI group. Similarly, the patients in the high HGI group had an increased risk of MACEs (HR = 1.247, 95% CI: 1.023-1.521, P = 0.029) as compared with patients in the medium HGI group. For ACM, CM, and MACEs, a U-shaped relation were found among these three groups. However, we did not find significant differences in the incidence of MACCEs among these three groups., Conclusion: The present study indicates that HGI could be an independent predictor for the risk of mortality and MACEs in patients with CAD., (© 2024. The Author(s).)

A series of 2-(trifluoromethyl)-4-hydroxyquinoline derivatives were designed and synthesized with introduction of the antibacterial fragment amino alcohols, and their antibacterial activity against plant phytopathogenic bacteria was evaluated for the development of quinoline bactericides. It is worth noting that compound Qa5 exhibited excellent antibacterial activity in vitro with a minimum inhibitory concentration (MIC) value of 3.12 μg/mL against Xanthomonas oryzae ( Xoo ). Furthermore, in vivo assays demonstrated that the protective efficacy of Qa5 against rice bacterial blight at 200 μg/mL (33.0%) was superior to that of the commercial agent bismerthiazol (18.3%), while the curative efficacy (35.0%) was comparable to that of bismerthiazol (35.7%). The antibacterial mechanisms of Qa5 indicated that it affected the activity of bacteria by inducing intracellular oxidative damage in Xoo and disrupting the integrity of the bacterial cell membrane. The above results demonstrated that the novel quinoline derivative Qa5 possessed excellent in vitro and in vivo antibacterial activity, indicating its potential as a novel green agricultural antibacterial agent.

Determining the differences in flower hydraulic traits and structural resource allocation among closely related species adapted to low mean annual precipitation (MAP) can provide insight into plant adaptation to arid environments. Here, we measured the maximum flower hydraulic conductance (K max-flower ), water potential at induction 50% loss of K max-flower (P 50-flower ), flower pressure-volume parameters, dry mass of individual flowers and structural components (vexillum, wings, keels, stamens and sepals) of six Caragana species growing in regions ranging from 110 to 1400 mm MAP. Compared with species from high-MAP environments, those from low-MAP environments presented lower K max-flower , more negative P 50-flower , osmotic potential at full turgor (π o ) and turgor loss points (π tlp ), and a greater bulk modulus of elasticity (ε). Consequently, a negative correlation between K max-flower (hydraulic efficiency) and P 50-flower (hydraulic safety) was observed across Caragana species. Furthermore, the dry masses of individual flowers and structural components (vexillum, wings, keels, stamens and sepals) were greater in the species from the low-MAP environment than in those from the high-MAP environment. These findings suggest that greater flower hydraulic safety and drought tolerance combined with greater structural resource allocation promote drought adaptation in Caragana species to low-MAP environments., (© 2024 John Wiley & Sons Ltd.)

Objective: To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer. Methods: The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N =36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N =22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P >0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results: Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z =-2.315, P =0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t =0.076, P =0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z =-1.331, P =0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ 2 =6.070, P =0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026-0.828, P =0.030). Conclusion: Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.

Sperm head morphology is crucial for male factor infertility diagnosis and assessment of male reproductive potential. Several criteria are available to analyze sperm head morphology, but they are limited by poor methodology comparability and population applicability. This study aimed to explore comprehensive and new normal morphometric reference values for spermatozoa heads in fertile Asian males. An automated sperm morphology analysis system captured 23 152 stained spermatozoa from confirmed fertile males. Of these samples, 1856 sperm head images were annotated by three experienced laboratory technicians as "normal". We employed 14 novel morphometric features to describe sperm head size (head length, head width, length/width ratio, and girth), shape (ellipse intersection over union, girth intersection over union, short-axis symmetry, and long-axis symmetry), area (head, acrosome, postacrosomal areas, and acrosome area ratio), and degrees of acrosome and nuclear uniformity. This straight-forward method for the morphometric analysis of sperm by accurate visual measurements is clinically applicable. The measured parameters present valuable information to establish morphometric reference intervals for normal sperm heads in fertile Asian males. The presented detailed measurement data will be valuable for interlaboratory comparisons and technician training. In vitro fertilization and andrology laboratory technicians can use these parameters to perform objective morphology evaluation when assessing male fertilization potential., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Background: Testicular cancer (TC) mostly occurs in men aged 14 to 44. Studies have shown that TC seriously damages male fertility, and 6% to 24% of patients with TC were even found to suffer from azoospermia when they are diagnosed. At present, some studies have pointed out that onco-microdissection testicular sperm extraction (mTESE) can extract sperm from tumor testicles. However, there are almost no reports on remedial measures after onco-mTESE failure. Given the valuable opportunity for fertility preservation in patients with TC and azoospermia, it is necessary to provide effective remedial methods for patients with failed onco-mTESE., Methods: Two young men, who were diagnosed with TC and also found to have azoospermia, tried onco-mTESE while undergoing radical orchiectomy for fertility preservation. However, sperm extraction failed in both patients. Subsequently, the isolated testicular tissue of the patient in case 1 suffered from TC again, and the patient in case 2 was scheduled to receive multiple cycles of gonadotoxic chemotherapy. Because both had a plan to have a birth in the future, we performed remedial mTESE., Results: Sperm was successfully extracted from both patients. The patient recovered well, without complications. The patient couple in case 1 underwent 1 intracytoplasmic sperm injection (ICSI) cycle but did not achieve clinical pregnancy., Conclusions: There is still an opportunity to extract sperm successfully using onco-mTESE, despite the difficulty of fertility preservation in TC patients with azoospermia. If sperm extraction from the tumor testis fails, implementing remedial mTESE as early as possible would likely preserve the last chance of fertility for these patients., Competing Interests: The authors declare that they have no funding and conflict of interests., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The aim of this article is to establish an external quality assessment (EQA) scheme for sperm Deoxyribonucleic acid (DNA) fragmentation (SDF) detection, and to assess the feasibility of the scheme. In addition, this article provides some case analysis of abnormal results in order to really help improve the performance of the laboratory., Results: In 2021 and 2022, 10 and 28 laboratories in China volunteered to participate in the EQA program respectively. Two samples were selected for EQA each year, a large spread of results was obtained for the four samples, and the highest values were 13.7, 4.2, 8.0 and 4.0 times the lowest respectively. The coefficients of variation (CVs) were very high for the four samples, at 46.6%, 30.1%, 26.7% and 30.3%, respectively. The CVs of the samples with high SDF values were lower than those of the samples with low SDF values. There was no significant difference between the results of sperm chromatin structure assay (SCSA) and sperm chromatin dispersion (SCD). For the 10 laboratories that participated in EQA in 2021 and 2022, the CVs of low SDF value samples and high SDF value samples decreased from 46.6% and 30.1% in 2021 to 32.5% and 22.7% in 2022, respectively., Conclusion: This is the first study to evaluate the EQA program on SDF, which involved a number of laboratories and was demonstrated to be feasible. It is recommended that all laboratories participate in the EQA of SDF to ensure the accuracy of the results., (© 2023. The Author(s).)

Objectives: To summarize the characteristics of local extension of eccentric and central nasopharyngeal carcinoma (NPC) by magnetic resonance imaging (MRI) and to improve clinical target volume (CTV) delineation., Methods: MRI of 870 newly diagnosed NPC patients were reviewed. According to tumor distribution features, the NPCs were divided into eccentric and central lesions., Results: All local invasions presented as continuous invasion from gross lesions and structures adjacent to the nasopharynx were more likely to be invaded. There were 240 (27.6%) and 630 (72.4%) cases with central and eccentric lesions, respectively. The spread of eccentric lesions was centered on the ipsilateral Rosenmüller's fossa; and most anatomic sites had significantly higher invasion rates in the ipsilateral side than the contralateral side (P < 0.05). However, they were at low risk of concurrent bilateral tumor invasion (<10%), except the prevertebral muscle (15.4%) and nasal cavity (13.8%). The extension of central NPCs was centered on the nasopharyngeal superior-posterior wall and was more common in the superior-posterior direction. Furthermore, bilateral tumor invasion into the anatomical sites was common., Conclusion: Local invasion of NPC was characterized by continuous invasion from proximal to distal sites. The eccentric and central lesions showed different invasion features. Individual CTV delineation should be based on the distribution characteristics of tumors. The eccentric lesions had a very low probability of invasion into the contralateral tissue; thus routine prophylactic radiation of contralateral parapharyngeal space and skull base foramina may not be necessary., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To investigate the value of CT radiomics features of meso-esophageal fat in the overall survival (OS) prediction of patients with locally advanced esophageal squamous cell carcinoma (ESCC)., Methods: A total of 166 patients with locally advanced ESCC in two medical centers were retrospectively analyzed. The volume of interest (VOI) of meso-esophageal fat and tumor were manually delineated on enhanced chest CT using ITK-SNAP. Radiomics features were extracted from the VOIs by Pyradiomics and then selected using the t-test, the Cox regression analysis, and the least absolute shrinkage and selection operator. The radiomics scores of meso-esophageal fat and tumors for OS were constructed by a linear combination of the selected radiomic features. The performance of both models was evaluated and compared by the C-index. Time-dependent receiver operating characteristic (ROC) analysis was employed to analyze the prognostic value of the meso-esophageal fat-based model. A combined model for risk evaluation was constructed based on multivariate analysis., Results: The CT radiomic model of meso-esophageal fat showed valuable performance for survival analysis, with C-indexes of 0.688, 0.708, and 0.660 in the training, internal, and external validation cohorts, respectively. The 1-year, 2-year, and 3-year ROC curves showed AUCs of 0.640-0.793 in the cohorts. The model performed equivalently compared to the tumor-based radiomic model and performed better compared to the CT features-based model. Multivariate analysis showed that meso-rad-score was the only factor associated with OS., Conclusions: A baseline CT radiomic model based on the meso-esophagus provide valuable prognostic information for ESCC patients treated with dCRT., (© 2023. The Author(s).)

Tumor-remodeled endothelial cells not only facilitate the formation of tumor angiogenesis but also promote tumorigenesis. In this study, we aimed to explore the interaction between glioma-associated endothelial cells (GAEs) and glioma cells. We found that different subtypes of glioma owned distinct GAE abundance. Glioma patients with high GAE abundance exhibited poor prognosis. Both the results of the bioinformatics analysis and the in vitro co-culture system assay revealed that GAE promoted glioma cell invasion. Besides, anti-vascular endothelial growth factor (VEGF) therapy partially abolished the effects of GAE on gliomas. Moreover, anti-VEGF therapy upregulated IL-2 expression in GAE, and exogenous IL-2 administration inhibits GAE-induced glioma cell invasion. Collectively, our present study provides a novel outstanding of the interaction between GAE and glioma cells., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cell-penetrating peptides (CPPs) are attractive non-viral gene delivery vectors due to their high transfection capacity and safety. Previously, we have shown that cell-penetrating peptide RALA can be a promising gene delivery vector for chronic wound regeneration application. In this study, we engineered a novel peptide called RALA-E by introducing elastin-derived VGVAPG fragment into RALA, in order to target the elastin-binding protein on the cell surface and thus improve delivery efficacy of RALA. The transfection efficiency of RALA-E was evaluated by transfecting the HEK-293T and HeLa cell lines cells with RALA-E/pDNA complexes and the flow-cytometry results showed that RALA-E significantly increased the transfection efficiency by nearly 20% in both cell lines compared to RALA. Inhibition of pDNA transfection on HEK-293T cells via chlorpromazine, genistein and mβCD showed that the inhibition extent in transfection efficiency was much less for RALA-E group compared to RALA group. In addition, RALA-E/miR-146a complexes showed up to 90% uptake efficiency in macrophages, and can escape from the endosome and enter the nucleus to inhibit the expression of inflammation genes. Therefore, the developed RALA-E peptide has high potential as a safe and efficient vector for gene therapy application.

This study is conducted to explore the association between health behaviors and the COVID-19 vaccination based on the risk compensation concept among health-care workers in Taizhou, China. We conducted a self-administered online survey to estimate the health behaviors among the staff in a tertiary hospital in Taizhou, China, from May 18 to 21 May 2021. A total of 592 out of 660 subjects (89.7%) responded to the questionnaire after receiving an e-poster on WeChat. Subjects who had been inoculated with the COVID-19 vaccine were asked to mention the differences in their health behaviors before and after the vaccination. The results showed that there were no statistical differences in health behaviors between vaccinated and unvaccinated groups, except in terms of the type of gloves they used (62.8% in the vaccinated group and 49.2% in the unvaccinated group, p = .048). Subjects who received earlier COVID-19 vaccinations exhibited better health behaviors (22.40% increased for duration of wearing masks ( P = .007), 25.40% increased for times of washing hands ( P = .01), and 20.90% increased for times of wearing gloves ( P = .01)). Subjects also revealed better health behaviors (washing hands, wearing gloves, and wearing masks) after vaccination compared to that before. In conclusion, concept of risk compensation was not applied in our findings. The health behaviors did not reduce after the COVID-19 vaccination, which even may improve health behaviors among health-care workers in the hospital setting.

A lack of confidence on the vaccination drive hinders the management of the COVID-19 pandemic. We aimed to assess the antibody response to the SARS-CoV-2 vaccine among hospitalized patients in China. This case-control study was based on SARS-CoV-2 sero-surveillance during hospitalization. From April to June 2021, hospitalized patients without documented COVID-19 infection from the Department of Urology were routinely assayed for anti-SARS-CoV-2 antibodies. The SARS-CoV-2 vaccination history of each participant was obtained from their vaccination records. Of the 405 participants, there were 37 seropositive participants (case group) and 368 seronegative participants (control group); 68 participants (16.8%) had received the inactivated SARS-CoV-2 vaccine, including 54 who received the Sinovac-CoronaVac vaccine and 14 received the Sinopharm vaccine. All seropositive participants who had received one or two doses of the SARS-CoV-2 vaccine were assessed for at least 16 days, while 31 (8.4%) of 368 seronegative controls who had received the vaccine were tested for 1-94 days. The overall seroconversion rate was 54.4% (37/68) in the vaccinated participants who received the inactivated SARS-CoV-2 vaccine. The odds ratio (OR) and confidence interval (CI) for seropositivity was 6.20 (95% CI: 2.05-18.71) in those received full vaccination with two doses versus those partially vaccinated participants with one dose after adjusting for sex and age. These findings imply that the inactivated SARS-CoV-2 vaccine could have a protective antibody response.

A community-based prostate cancer screening program was conducted to assess the morbidity and associated factors for prostate cancer among the subpopulation of men aged ≥50 years in Taizhou, China. Taizhou Integrated Prostate Screening (TIPS) is a large, observational, population-based study of prostate cancer screening data based on serum prostate-specific antigen (PSA) concentrations. A pilot census of all male residents aged 50 years or older was conducted in Luqiao District, one of the field sites of the TIPS cohort in the city of Taizhou, Zhejiang. The interviewer-administered questionnaire evaluated demographic characteristics and environmental exposure factors. A total of 1,806 out of 3,516 participants completed the questionnaire. The overall prevalence of PSA ≥4 ng/mL was 11.5%, and included participants at low risk (9.2%), moderate risk (1.7%), and high risk (0.6%). Participants aged 60-69, 70-79, and ≥80 years had a 2.7-fold, 4.2-fold, and 6.5-fold higher risk of elevated PSA, respectively, in comparison with those aged 50 to 59 years ( p < .001). Eighteen patients were diagnosed with prostate cancer, of whom 11 (61.1%) underwent radical surgery. This community-based PSA screening program indicated the results for early detection of prostate cancer among men aged ≥50 years. Early screening and appropriate clinical therapy for the management of prostate cancer are essential in this subpopulation.

Wurfbainia villosa is a well-known medicinal and edible plant that is widely cultivated in the Lingnan region of China. Its dried fruits (called Fructus Amomi) are broadly used in traditional Chinese medicine for curing gastrointestinal diseases and are rich in volatile terpenoids. Here, we report a high-quality chromosome-level genome assembly of W. villosa with a total size of approximately 2.80 Gb, 42 588 protein-coding genes, and a very high percentage of repetitive sequences (87.23%). Genome analysis showed that W. villosa likely experienced a recent whole-genome duplication event prior to the W. villosa-Zingiber officinale divergence (approximately 11 million years ago), and a recent burst of long terminal repeat insertions afterward. The W. villosa genome enabled the identification of 17 genes involved in the terpenoid skeleton biosynthesis pathway and 66 terpene synthase (TPS) genes. We found that tandem duplication events have an important contribution to the expansion of WvTPSs, which likely drove the production of volatile terpenoids. In addition, functional characterization of 18 WvTPSs, focusing on the TPS-a and TPS-b subfamilies, showed that most of these WvTPSs are multi-product TPS and are predominantly expressed in seeds. The present study provides insights into the genome evolution and the molecular basis of the volatile terpenoids diversity in W. villosa. The genome sequence also represents valuable resources for the functional gene research and molecular breeding of W. villosa., (© 2022 Society for Experimental Biology and John Wiley & Sons Ltd.)

Background: Prior reports have indicated that the abnormal expression of small nuclear ribonucleoproteins (snRNPs) genes is related to malignant tumors. However, in hepatocellular carcinoma (HCC), the precise role of snRNPs is not well understood. Therefore, the purpose of this study was to evaluate the prognostic roles of SNRPB/D1/D2/D3/E/F/G and their correlation to immune infiltration in HCC., Methods: The study was carried out via the following databases, software, and experimental validation: ONCOMINE, GEPIA2, UALCAN, The Cancer Genome Atlas, Gene Expression Omnibus, ArrayExpress, Kaplan-Meier plotter, cBioPortal, STRING, DAVID 6.8, TIMER, Cytoscape software, and immunohistochemistry experiments., Results: Overexpressed SNRPB/D1/D2/D3/E/F/G proteins were found in HCC tissues. The transcription levels of 7 snRNPs genes were related to the TP53 mutation and tumor grades. SNRPB/D1/D2/D3/F/G expression was significantly correlated with cancer staging, whereas SNRPE was not. Moreover, Kaplan-Meier survival analysis showed that upregulation of SNRPB/D1/D2/E/G was relevant to worse OS in HCC patients, especially in patients with alcohol consumption and those without viral hepatitis. Multivariate Cox regression analysis indicated that expression of SNRPB/D1/D3/E/F/G were independent prognostic factors for unfavorable OS in HCC. In addition, a high mutation rate of snRNPs genes (44%) was also found in HCC. The mRNA expression levels of snRNPs were meaningfully and positively related to six types of infiltrating immune cells (B cells, CD4 + T cells, CD8 + T cells, neutrophil, macrophage, and dendritic cells). Also, SNRPB/D1/G genes were significantly associated with molecular markers of various immune cells in HCC., Conclusions: SNRPB/D1/D3/E/F/G are potential prognostic biomarkers for a short OS in HCC, and SNRPB/D1/G were novel immune therapy targets in HCC patients., Competing Interests: None., (AJTR Copyright © 2022.)

Inflammation is a hallmark of cancers. The purpose of the present study was to evaluate the prognostic potential of hematological inflammatory markers in glioblastoma multiforme (GBM) patients. The clinical data of 99 patients with lower-grade gliomas and 88 patients with GBMs were retrospectively analyzed. The optimal cutoff values for peripheral markers were determined by X-tile. Kaplan-Meier and Cox proportional hazard regression analyses were performed to identify markers with prognostic significance. Several scoring systems were constructed by combining these prognostic markers. The predictive accuracies of nomograms incorporating these scoring systems were evaluated by Harrell's concordance index and receiver operating characteristic curve analysis. GBM patients exhibited higher neutrophil counts (p=0.001), neutrophil-to-lymphocyte ratio (NLR) (p<0.001), and platelet-to-lymphocyte ratio (PLR) (p=0.001), as well as lower lymphocyte counts (p=0.023), lymphocyte-to-monocyte ratio (LMR) (p=0.015), and albumin-to-globulin ratio (AGR) (p=0.003) than those with lower-grade gliomas. Multivariate analysis indicated that a high NLR (> 2.0) (Hazard ratio[HR]=2.519, 95% confidence interval (CI): 1.220-5.204, p=0.013), low LMR (< 2.3) (HR=2.268, 95%CI: 1.172-4.386, p=0.015), or low AGR (< 1.7) (HR=2.924, 95%CI: 1.389-6.135, p=0.005) were associated with poor overall survival in GBM patients. The scoring systems of AGR-NLR, AGR-LMR, and LMR-NLR were associated with GBM survival. The nomogram integrating AGR-NLR score had the best efficacy in predicting GBM survival (c-index=0.874). Pretreatment scores of AGR-NLR, AGR-LMR, and LMR-NLR may serve as prognostic factors for GBM patients, and a nomogram integrating AGR-NLR may provide a reliable tool to facilitate personalized preoperative evaluations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Lan, Wang, Huang, Li, Li, Li, Li, Wang and Li.)

High immune-cell infiltration in glioblastomas (GBMs) leads to immunotherapy resistance. Emerging evidence has shown that zinc finger Asp-His-His-Cyc-type (ZDHHC) palmitoyl transferases participate in regulating tumor progression and the immune microenvironment. In the present study, a large cohort of patients with gliomas from The Cancer Genome Atlas (TCGA) and Rembrandt databases was included to perform omics analysis of ZDHHCs in gliomas. CCK-8, flow cytometry, quantitative real-time PCR, western blotting, and transwell assays were performed to determine the effects of ZDHHC inhibition on glioma cells and microglia. We found that five (ZDHHC11, ZDHHC12, ZDHHC15, ZDHHC22, and ZDHHC23) out of 23 ZDHHCs were aberrantly expressed in gliomas and might play their roles through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. Further results indicated that inhibition of ZDHHCs with 2-bromopalmitate (2-BP) suppressed glioma-cell viability and autophagy, as well as promoted apoptosis. Targeting ZDHHCs also promoted the sensitivity of glioma cells to temozolomide (TMZ) chemotherapy. In addition, the inhibition of ZDHHCs weakened the migratory ability of microglia induced by glioma cells in vitro and in vivo . Taken together, our findings suggest that the inhibition of ZDHHCs suppresses glioma-cell viability and microglial infiltration. Targeting ZDHHCs may be promising for glioma treatments., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Endometrial mesenchymal stem cells (eMSCs) are undifferentiated endometrial cells with self-renewal, multidirectional differentiation and high proliferation potential. Nowadays, eMSCs have been found in a few species, but it has never been reported in endangered wild animals, especially the red panda. In this study, we successfully isolated and characterized the eMSCs derived from red panda. Red panda eMSCs were fibroblast-like, had a strong proliferative potential and a stable chromosome number. Pluripotency genes including Klf4 , Sox2 and Thy1 were highly expressed in eMSCs. Besides, cultured eMSCs were positive for MSC markers CD44, CD49f and CD105 and negative for endothelial cell marker CD31 and haematopoietic cell marker CD34. Moreover, no reference RNA-seq was used to analyse the eMSCs transcriptional expression profile and key pathways. Compared with skin fibroblast cell group, 9104 differentially expressed genes (DEGs) were identified, among which are 5034 genes upregulated, 4070 genes downregulated and the top 20 enrichment pathways of DEGs in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes Genomes (KEGG) mainly associated with G-protein coupled receptor signalling pathway, carbohydrate derivative binding, nucleoside binding, ribosome biogenesis, cell cycle, DNA replication, Ras signalling pathway and purine metabolism. Among the DEGs, some representative genes about promoting MSCs differentiation and proliferation were upregulated and promoting fibroblasts proliferation were downregulated in eMSCs group. Red panda eMSCs also had multiple differentiation ability and could differentiate into adipocytes, chondrocytes and hepatocytes. In conclusion, we, for the first time, isolated and characterized the red panda eMSCs with ability of multiplication and multilineage differentiation in vitro . The new multipotential stem cell could be beneficial not only for the germ plasm resources conservation of red panda, but also for basic or pre-clinical studies in the future., (© The Author(s) 2022. Published by Oxford University Press and the Society for Experimental Biology.)

Immunotherapy has developed rapidly and has gradually become one of the important methods for treatment of gastric cancer (GC). The research on tumor infiltrating immune cells (TIICs) and immune-related genes in the tumor microenvironment (TME) greatly encourages the development of immunotherapy. The devolution algorithm (CIBERSORT) was applied to infer the proportion of 22 TIICs based on gene expression profiles of GC tissues, which were downloaded from TCGA and GEO. TCGA was utilized to analyze the differential expression of immune-related genes, and explore the potential molecular functions of these genes. We have observed the enrichment of multiple TIICs in microenvironment of GC. Some of these cells were closely related to tumor mutational burden (TMB), microsatellite instability (MSI), Fuhrman grade, and TNM staging. Survival analysis showed that the infiltration level of CD8 + T cells, activated CD4 + memory T cells and M2 macrophages were significantly related to the prognosis of GC patients. The functional enrichment analysis of immune-related genes revealed that these genes were mainly associated with cytokine activation and response. Four significant modules were screened by PPI network and 20 key genes were screened from the modules. The expression levels of CALCR and PTH1R are strikingly related to the expression of immune checkpoint and the prognosis of GC patients. The type and number of TIICs in microenvironment of GC, as well as immune-related genes are closely related to tumor progression, and can be used as important indicators for patient prognosis assessment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Yuan, Liang, Zhang, Li, Xie, Li, Jiang, Li, Shen, Pang, Zou, Zhou, Li and Hu.)

Background: Multiple endocrine neoplasia type 2A (MEN 2A) is mainly caused by germline RET codon C634 mutation and is characterized by Medullary Thyroid Carcinoma (MTC), pheochromocytoma (PHEO), and hyperparathyroidism (HPTH). The early diagnosis and initial normative treatment are helpful for the long-term outcome of MEN2A., Methods: Three index cases and their 29 relatives from three families with MEN2A were included in this study. Genetic screening was performed on all participants. Demographic, clinical profiles, tumor histopathologic features, and follow-up records were systematically analyzed., Results: In total, RET C634Y mutation was identified in 10 individuals (10/32, 31.3%). Among them, 5 presented with MTC symptoms, whereas the other 5 did not show apparent clinical manifestation, and all were subjected to thyroidectomy with varying neck dissection. Compared to individuals in the former, the latter benefited greatly from RET screening with significantly younger age at diagnosis of MTC and surgery (18.1 ± 13.8 years vs. 39.0 ± 14.1 years, P =0.045), and lessaggressive MTC behavior (size: 0.74 vs. 2.82 cm, P =0.026; LN+/resected: 20.0% vs. 100.0%, P =0.048) and also lower recurrence rate of MTC (20.0% vs. 100.0%, P =0.048). The PHEO was identified in 6 of the 10 carriers (60.0%), and all had undergone adrenal-sparing surgery. During the 10 years of follow-up, one (16.7%) developed recurrence of PHEO., Conclusion: Integrated RET screening, serum calcitonin, and plasma metanephrine/ normetanephrine levels can facilitate the early diagnosis and standardized MTC/PHEO surgery to improve the prognosis of MEN2A. Laparoscopic adrenal-sparing surgery prior to the bilateral total thyroidectomy is a preferred surgical approach for PHEO., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Type 2 diabetes mellitus (T2DM) is among the most remarkable public health concerns globally. Accumulating research evidence documents that alteration of gut microbiota has an indispensable role in the onset and progression of obesity and T2DM. A reduced microbial diversity is linked to insulin resistance and energy metabolism, especially for the rise of the Firmicutes / Bacteroidetes ratio. Changes in metabolites followed by the gut dysbacteriosis are linked to the presence of T2DM. Moreover, endotoxin leakage and gut permeability caused by gut dysbacteriosis is more of a trigger for the onset and progression of T2DM. Research documents that natural products are remarkable arsenals of bioactive agents for the discovery of anti-T2DM drugs. Many studies have elucidated that the possible mechanisms of the anti-T2DM effects of natural products are remarkably linked to its regulation on the composition of gut microflora and the successive changes in metabolites directly or indirectly. This review presents a brief overview of the gut microbiota in T2DM and several relevant mechanisms, including short-chain fatty acids, biosynthesis and metabolism of branched-chain fatty acids, trimethylamine N-oxide, bile acid signaling, endotoxin leakage, and gut permeability, and describes how dietary natural products can improve T2DM via the gut microbiota., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To evaluate the association between body composition and subsequent risk of the major gynecologic malignancies., Methods: This is a prospective analysis of participants from the UK Biobank. We measured baseline body composition and confirmed cancer diagnosis through linkage to cancer and death registries. We evaluated hazard ratios (HRs) and confidence interval (CIs) with COX models adjusting for potential confounders., Results: We document 1430 cases of the top three gynecologic malignancies (uterine corpus cancer 847 cases, ovarian cancer 514 cases, and cervical cancer 69 cases) from 245,084 female participants (75,307 were premenopausal and 169,777 were postmenopausal). For premenopausal women, whole body fat-free mass (WBFFM) was associated with an increased risk of uterine corpus cancer (Adjusted HR per unit increase 1.04, 95% CI 1.02-1.06). For postmenopausal women, compared with the first quartile, the fourth quartile of WBFFM and whole body fat mass(WBFM) was associated with 2.16 (95% CI 1.49-3.13) times and 1.89 (95% CI 1.31-2.72) times of increased uterine corpus cancer risk, respectively. Regarding the distribution of body fat mass (FM)/fat-free mass (FFM), FFM distributed in the trunk was associate with increased uterine corpus cancer risk in premenopausal (HR 1.18,95% CI 1.07-1.31) and postmenopausal women (HR 1.13,95% CI 1.09-1.18). Meanwhile, FM/FFM distributed in the limbs present an U-shaped associations with uterine corpus cancer risk. We did not observe any association between aforementioned body composition indices with ovarian or cervical cancer., Conclusion: FM is associated with an increased risk of uterine corpus cancer in postmenopausal women. Meanwhile, FFM is found to be a risk factor for uterine corpus cancer in both premenopausal and postmenopausal women. No association of body composition with ovarian or cervical cancer was observed., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Macrophages are a double-edged sword with potential cancer-promoting and anticancer effects. Controversy remains regarding the effect of macrophages, especially M1 macrophages, on tumor promotion and suppression. We aimed to investigate the role of M1 macrophages in the occurrence and progression of esophageal squamous cell carcinoma (ESCC). Analyzing the data in Gene Expression Omnibus database by the CIBERSORT algorithm found that M1 macrophages were one of the important components of many immune cells in ESCCs, and the increase in their number was obviously negatively correlated with tumor T staging. This result was verified by our experimental data: the density of CD68/HLA-DR double-stained M1 macrophages in ESCC tumor nest and tumor stroma was significantly higher than that in cancer-adjacent normal (CAN) tissues. The density of M1 macrophages in ESCC tumor nest was negatively correlated with the patient's lymph node metastasis and clinical stage (P < 0.05), and the negative tendency was more obvious for M1 macrophages in ESCC tumor stroma (P < 0.001). Exposure to M1 macrophage-conditioned medium inhibited ESCC cell migration and invasion ability significantly (P < 0.05). Moreover, the increased M1 macrophage density in ESCC tumor stroma correlated positively with good prognosis of ESCC. M1 macrophages were involved in inhibiting ESCC cell migration and invasion, which could serve as a good prognostic factor in patients with ESCC., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Drought is a cyclical phenomenon in natural environments. During dehydration, stomatal closure is mainly regulated by abscisic acid (ABA) dynamics that limit transpiration in seed plants, but following rehydration, the mechanism of gas exchange recovery is still not clear. In this study, leaf water potential (ψ leaf ), stomatal conductance (g s ), leaf hydraulic conductance (K leaf ), foliar ABA level, ethylene emission rate in response to dehydration and rehydration were investigated in four Caragana species with isohydric (Caragana spinosa and C. pruinosa) and anisohydric (C. intermedia and C. microphylla) traits. Two isohydric species with ABA-induced stomatal closure exhibited more sensitive g s and K leaf to decreasing ψ leaf than two anisohydric species which exhibited a switch from ABA to water potential-driven stomatal closure during dehydration. Following rehydration, the recovery of gas exchange was not associated with a decrease in ABA level but was strongly limited by the degradation of the ethylene emission rate in all species. Furthermore, two anisohydric species with low drought-induced ethylene production exhibited more rapid recovery in gas exchange upon rehydration. Our results indicated that ethylene is a key factor regulating the drought-recovery ability in terms of gas exchange, which may shape species adaptation to drought and potential species distribution., (© 2020 John Wiley & Sons Ltd.)

The immune response facilitated by tumor-associated macrophages is a vital determinant of tumor progression. We identified differentially expressed genes between various macrophage phenotypes in the Gene Expression Omnibus, and used Kaplan-Meier Plotter to determine which of them altered the prognosis of esophageal carcinoma patients. Fibrinogen-like protein 2 ( FGL2 ), an immunosuppressive factor in the tumor microenvironment of various cancers, was upregulated in M2 macrophages, and higher FGL2 expression was associated with poorer survival in esophageal carcinoma patients. Using the TIMER database, we found that FGL2 expression correlated positively with the levels of immune markers of infiltrating B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells in esophageal carcinoma samples. Correlation analyses in cBioPortal revealed that the mRNA levels of FGL2 correlated strongly with those of interleukin 10, matrix metalloproteinase 9, C-C motif chemokine ligand 5, T-cell immunoglobulin mucin 3, interleukin 13, vascular cell adhesion molecule 1, macrophage colony-stimulating factor and fibroblast growth factor 7 in esophageal carcinoma tissues. The same cytokines were upregulated when esophageal squamous cell carcinoma cells were co-cultured with M2-like tumor-associated macrophages. Thus, by secreting FGL2, M2-like tumor-associated macrophages may create an immunosuppressive tumor microenvironment that induces the occurrence and progression of esophageal carcinoma.

Women with polycystic ovary syndrome (PCOS) are characterized by endocrine disorders accompanied by a decline in oocyte quality. In this study, we generated a PCOS mice model by hypodermic injection of dehydroepiandrosterone, and metformin was used as a positive control drug to study the effect of pachymic acid (PA) on endocrine and oocyte quality in PCOS mice. Compared with the model group, the mice treated with PA showed the following changes (slower weight gain, improved abnormal metabolism; increased development potential of GV oocytes, reduced number of abnormal MII oocytes, and damaged embryos; lower expression of ovarian-related genes in ovarian tissue and pro-inflammatory cytokines in adipose tissue). All these aspects show similar effects on metformin. Most notably, PA is superior to metformin in improving inflammation of adipose tissue and mitochondrial abnormalities. It is suggested that PA has the similar effect with metformin, which can improve the endocrine environment and oocyte quality of PCOS mice. These findings suggest that PA has the similar effect with metformin, which can improve the endocrine environment and oocyte quality of PCOS mice., (© The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Remediation of gold tailings is often difficult due to their extremely barren nature and highly heavy metal concentrations. Returning green manure and applying sewage sludge compost have the beneficial effects of providing nutrients and improving the soil environment. The effects of green manure plants, alfalfa (Medicago sativa L.), ryegrass (Lolium perenne Linn.), and tall fescue (Festuca arundinacea), returning in situ on nutrients, bioavailability of trace metals, and community structure of microorganism in gold tailings amended with 0%, 5%, and 10% (weight/weight) sewage sludge compost on the top 4 cm of tailings (SSC-5, SSC-10) were investigated in a pot experiment. The results showed that the plant biomass and microbial biomass carbon in tailings significantly increased in the treatments with sewage sludge compost. The available N and available P and the availability of Zn decreased markedly with the returning of alfalfa and ryegrass. Moreover, through high-throughput sequencing, it was found that the returning of alfalfa had positive effects on the bacterial community richness but a negative impact on the fungal community richness. The microbial community diversity was reduced in the treatment without sewage sludge compost amendment and with alfalfa returning. However, the microbial community diversity was enriched in the treatment of alfalfa returning with sewage sludge compost. In each plant species, 9 dominant bacterial phyla and 10 dominant fungi phyla could be detected. Returning alfalfa green manure and applying sewage sludge compost led to a relative increase in the abundance of Proteobacteria and Ascomycota. These results demonstrated that returning alfalfa and applying sewage sludge compost could be effective in the ecological restoration of gold tailings.

Aim: Male obesity-associated secondary hypogonadism (MOSH) is becoming a public health issue. We aimed to know MOSH among young and middle-aged men in our hospital, to analyse their sex hormones and other index, and to determine leptin as a risk factor for MOSH., Methods: In total, 258 men (ages ranging from 20 to 60, mean 38 ± 15) were enrolled in this study, and 242 of these men had their complete data, body mass index (BMI), waist circumference and sex hormones retrospectively investigated. The leptin and lipid levels were also evaluated, and comparisons were made between young (20-39 years old) and middle-aged (40-60 years old) men., Results: Among all the participants, 7 were thin, with a BMI < 18.5 kg/m 2 , 95 had a normal BMI (18.5 ≤ BMI < 23.9 kg/m 2 ), 87 (35.9%) were overweight (24 ≤ BMI ≤ 27.9 kg/m 2 ) and 53 (21.9%) were obese (BMI ≥ 28 kg/m 2 ), 173 (71.5%) had a waist sized ≥ 85 cm. Among the 242 men, 104 (43%) had hypogonadism (TT ≤ 331.412 ng/dL). Compared with the men of normal weight, the level of testosterone of the obese men decreased (P = .006), while the level of serum lipids (including total cholesterol, TG and low-density lipoprotein cholesterol, P < .05) was elevated, higher UA, FSH and leptin were also present in the obese men. There were 83 (34.2%) men with MOSH. Compared with middle-aged men with MOSH, the FSH in young men was significantly reduced (P < .05); no significant increase in estradiol was observed in the MOSH group. The leptin levels in the MOSH group were significantly higher than those in the hypogonadism only group (P < .001)., Conclusion: Obesity increases the prevalence of hypogonadism. The decrease in testosterone levels in young men maybe due to inhibition of the hypothalamic pituitary gonadal axis. Leptin is an independent risk factor for MOSH., (© 2020 John Wiley & Sons Ltd.)

Mesenchymal stem cells (MSC) have strong therapeutic potential due to their capacity for self-renewal and multilineage differentiation. MSCs can also be useful in preserving the current genetic diversity of endangered wildlife. To date, MSCs from various species have been studied, but only a few species of endangered wild animals have been reported. Adult bone marrow (BM) is a rich source of mesenchymal stem cells. The aim of this study was to isolate and characterize MSCs derived from the BM of red pandas. Red panda BM-MSCs isolated from five individuals were fibroblast-like cells, similar to other species. Cultured BM-MSCs with normal karyotype were negative for the hematopoietic line marker CD34 and the endothelial cell marker CD31 but were positive for MSC markers, including CD44, CD105 and CD90. RT-PCR and western blot analysis showed self-renewal and pluripotency genes, including Oct4, Sox2 and Klf4, were also expressed in red panda BM-MSCs. Finally, red panda BM-MSCs had the potential for differentiation into osteogenic, adipogenic and neuron-like cells by using a combination of previously reported protocols for other species. We have therefore demonstrated that cells harvested from red panda bone marrow are capable of extensive in vitro multiplication and multilineage differentiation, which is an essential step toward their use in the preservation of red pandas biological diversity and future studies on MSC applications in endangered species., (Copyright © 2020 Elsevier GmbH. All rights reserved.)