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ObjectiveGender differences are prevalent in major depressive disorder (MDD), but the gender differences in the relationship between comorbid anxiety and thyroid hormones in young first-episode and drug-naive (FEND) MDD patients are unknown.MethodsA total of 1,289 young outpatients with FEDN MDD were recruited. Demographic and clinical data were collected for each patient. The patient’s blood glucose, blood pressure, thyroid hormone, and thyroid antibody levels were measured. The Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) were used to assess patients’ depression, anxiety, and positive symptoms, respectively.ResultsThe prevalence of comorbid anxiety disorders was 80.4 and 79.4% in male and female MDD patients, respectively. Patients with anxiety had higher HAMD and PANSS scores, higher serum thyroid stimulating hormone (TSH), anti-thyroglobulin antibody (A-TG), and thyroid peroxidase antibody (A-TPO) levels, higher blood glucose and blood pressure levels, and more patients with psychotic symptoms and suicide attempts. Male patients were younger and had a younger age of onset. Logistic regression analysis showed that HAMD score and comorbid suicide attempts were significant predictors of anxiety symptoms in both males and females, whereas A-TG predicted anxiety symptoms in female patients only. Limitations: No causal relationship could be drawn due to the cross-sectional design.ConclusionThis study showed gender differences in factors associated with anxiety symptoms in patients with MDD. Some factors were associated with anxiety symptoms in both male and female patients, while A-TG was only associated with anxiety symptoms in female patients.

Abstract Background Schizophrenia is a complex mental illness with significant sex differences. Cognitive impairment is common in patients with schizophrenia, even in remission. This study was designed to examine the sex differences in the relationship between cognitive impairment and clinical correlations with first-episode drug-naïve (FEDN) schizophrenia. Methods 93 FEDN patients (male/female = 45/48) and 160 controls (male/female = 74/86) were enrolled to compare the sex differences in cognitive functions measured by the MATRICS Consensus Cognitive Battery (MCCB). Positive and Negative Syndrome Scale (PANSS) and Hamilton Depression Scale (HAMD) were used to evaluate patients' clinical symptoms. We compared cognitive impairment with sociodemographic characteristics and measures of different genders, as well as group-by-sex interactions. Results Our results showed that male patients had significantly lower scores for symbol coding, digital sequence, and verbal learning than female patients, while the healthy controls showed similar sex differences. In female patients, multiple linear regression analysis confirmed that PANSS negative symptoms and general psychopathology scores, HAMD total score, and education level were independent contributors to MCCB total score. In male patients, only education was an independent contributor to MCCB total score. Conclusions These findings revealed significant sex differences in cognitive impairments and clinical symptoms in FEDN, which will be worthy of a follow-up study of schizophrenia in the future.

Abstract Phytochrome interacting factors (PIFs) serve as crucial regulators in the light signal transduction pathway and also mediate light signals to regulate secondary metabolite synthesis in plants. However, the regulator role of PIFs in secondary metabolites often varies among different plants. Isorhynchophylline (IRN), an iconic secondary metabolite of Uncaria rhynchophylla, holds significant medicinal value. Low light induces the synthesis of IRN in previous research, but PIFs in U. rhynchophylla have not been studied to date. Building on this, we identified a PIF protein, UrPIF3, which possesses the typical conserved domains of the PIFs and is localized in the nucleus. Moreover, the expression level of UrPIF3 is consistently positively correlated with the expression of two key enzyme genes (UrSGD and UrSTR) in the IRN biosynthesis pathway, regardless of whether under low light or restoring light conditions. Yeast one-hybrid and dual-luciferase assays further demonstrated that UrPIF3 can directly upregulate UrSGD. Conversely, silencing UrPIF3 inhibits IRN synthesis, and significantly reduces the expression levels of UrSGD and UrSTR. In summary, our results suggest that under low light conditions, UrPIF3 can directly upregulate UrSGD and indirectly upregulate UrSTR, thereby promoting the synthesis of IRN.

C27H19NiN3O5, monoclinic, P21/c (no. 14), a = 11.082(1) Å, b = 10.480(1) Å, c = 22.719(2) Å, β = 117.76(4)°, V = 2334.9(9) Å3, Z = 4, R gt(F) = 0.0489, wR ref(F 2) = 0.1271, T = 293 K.

Abstract Objectives In comparison to the subjects without diabetes, a greater concentration of serum carbohydrate antigen 19 − 9 (CA 19 − 9) was observed in the subjects with diabetes. Nevertheless, since the occurrence of abnormal CA 19 − 9 is not widespread among the whole diabetic population, this phenomenon has not attracted enough attention. The prevalence of abnormal CA 19 − 9 in hospitalized patients with diabetes was the focus of our research. Method A total of 385 subjects with diabetes and 200 controls were enrolled and all had been tested the CA19-9 levels. Cases of cancers were excluded through examination and followup for 1 year. Results We found that the rate of patients with abnormal CA19-9 level was 8.3%. The rate of patients with abnormal CA19-9 level was 14.0% in the HbA1c ≥ 9% group, and 3.0% in the HbA1c

This paper presents an experimental study on the compressive properties and creep behavior of Mg-Gd-Y-Zn-Mn-Nd alloy. A total of 42 specimens are prepared and tested, including 18 compression tests and 24 creep tests. The investigation aims to evaluate the influence of material orientation, temperature, and initial stress (for creep test only) on the compressive behavior of the Mg-Gd-Y-Zn-Mn-Nd alloy. First, the results of compression tests are analyzed, revealing insights into the anisotropic behavior, failure mode, yield strength, ultimate compressive strength, and failure strain of the Mg-Gd-Y-Zn-Mn-Nd alloy under compressive loading. Then, according to the experimental data from creep tests, where the steady creep rate, stress exponent and activation energy are calibrated. Furthermore, the creep mechanisms of the Mg-Gd-Y-Zn-Mn-Nd alloy under various material orientations are discussed. Additionally, the authors analyze and compare the Electron Backscatter Diffraction (EBSD) data of the Mg-Gd-Y-Zn-Mn-Nd alloy before and after undergoing compressive creep. Finally, based on the test results, a mathematical model is proposed to describe the development of compressive creep strain.

BackgroundEndometriosis (EM) is a prevalent gynecological disorder frequently associated with irregular menstruation and infertility. Programmed cell death (PCD) is pivotal in the pathophysiological mechanisms underlying EM. Despite this, the precise pathogenesis of EM remains poorly understood, leading to diagnostic delays. Consequently, identifying biomarkers associated with PCD is critical for advancing the diagnosis and treatment of EM.MethodsThis study used datasets from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) following preprocessing. By cross-referencing these DEGs with genes associated with PCD, differentially expressed PCD-related genes (DPGs) were identified. Enrichment analyses for KEGG and GO pathways were conducted on these DPGs. Additionally, Mendelian randomization and machine learning techniques were applied to identify biomarkers strongly associated with EM.ResultsThe study identified three pivotal biomarkers: TNFSF12, AP3M1, and PDK2, and established a diagnostic model for EM based on these genes. The results revealed a marked upregulation of TNFSF12 and PDK2 in EM samples, coupled with a significant downregulation of AP3M1. Single-cell analysis further underscored the potential of TNFSF12, AP3M1, and PDK2 as biomarkers for EM. Additionally, molecular docking studies demonstrated that these genes exhibit significant binding affinities with drugs currently utilized in clinical practice.ConclusionThis study systematically elucidated the molecular characteristics of PCD in EM and identified TNFSF12, AP3M1, and PDK2 as key biomarkers. These findings provide new directions for the early diagnosis and personalized treatment of EM.

Summary: Bacteria dysbiosis and its accompanying inflammation or compromised mucosal integrity is associated with an increased risk of HIV-1 transmission. However, HIV-1 may also bind bacteria or bacterial products to impact infectivity and transmissibility. This study evaluated HIV-1 interactions with bacteria through glycan-binding lectins. The Streptococcal Siglec-like lectin SLBR-N, a part of the fimbriae shrouding the bacteria surface that recognizes α2,3 sialyated O-linked glycans, was noted for its ability to enhance HIV-1 infectivity in the context of cell-free infection and cell-to-cell transfer. Enhancing effects were recapitulated with O-glycan-binding plant lectins, signifying the importance of O-glycans. N-glycan-binding bacterial lectins FimH and Msl had no effect. SLBR-N was demonstrated to capture and transfer infectious HIV-1 virions, bind to O-glycans on HIV-1 Env, and increase HIV-1 resistance to neutralizing antibodies targeting different regions of Env. This study highlights the potential contribution of O-glycan-binding lectins from commensal bacteria at the mucosa in promoting HIV-1 infection.

Abstract Purpose To report the planning benchmark case results of the POTENTIAL trial—a multicenter, randomized, phase 3 trial—to evaluate the value of internal mammary nodal (IMN) irradiation for patients with high-risk breast cancer. Methods All participating institutions were provided the outlines of one benchmark case, and they generated radiation therapy plans per protocol. The plans were evaluated by a quality assurance team, after which the institutions resubmitted their revised plans. The information on beams arrangement, skin flash, inhomogeneity corrections, and protocol compliance was assessed in the first and final submission. Results The plans from 26 institutions were analyzed. Some major deviations were found in the first submission. The protocol compliance rates of dose coverage for the planning target volume of chest wall, supraclavicular fossa plus axilla, and IMN region (PTVim) were all significantly improved in the final submission, which were 96.2% vs. 69.2%, 100% vs. 76.9%, and 88.4% vs. 53.8%, respectively. For OARs, the compliance rates of heart Dmean, left anterior descending coronary artery V40Gy, ipsilateral lung V5Gy, and stomach V5Gy were significantly improved. In the first and final submission, the mean values of PTVim V100% were 79.9% vs. 92.7%; the mean values of heart Dmean were 11.5 Gy vs. 9.7 Gy for hypofractionated radiation therapy and 11.5 Gy vs. 11.0 Gy for conventional fractionated radiation therapy, respectively. Conclusion The major deviations were corrected and protocol compliance was significantly improved after revision, which highlighted the importance of planning benchmark case to guarantee the planning quality for multicenter trials.

The effect of ZnO on phase composition, microstructure, thermal and dielectric properties of AlN ceramics was studied. The X-ray diffraction indicated that ZnAl2O4 and ZnO phases were detected in samples. With 0.5 wt% ZnO added, the thermal conductivity of AlN sample increased to 193.7 W/m·K. Whereas, the thermal conductivity dropped sharply due to excess ZnO. Moreover, the addition of ZnO increased the permittivity and altered the relaxation mechanism of AlN ceramics. The fitting data and activation energy from impedance spectroscopy revealed the variation of defect mechanisms in samples. The addition of 0.5 wt% ZnO reduced the concentration of aluminum vacancy in AlN grains to improve thermal conductivity. Nevertheless, excess ZnO dissolved into the AlN lattice and created additional defects, causing the decrease in thermal conductivity and electrical resistivity for AlN ceramics. Overall, suitable addition of ZnO can effectively increase the thermal conductivity and alter the dielectric properties of AlN ceramics.

ObjectiveTo investigate the effect of two postoperative doses of estradiol valerate (2 and 4 mg/day) on reproductive outcomes in patients with moderate to severe intrauterine adhesions (IUAs).MethodsA retrospective cohort study was conducted at a single tertiary reproductive medical center between January 2018 and December 2019 to compare the reproductive outcomes of two doses of estradiol valerate (2 and 4 mg daily) after hysteroscopic adhesiolysis. All patients received adjuvant postoperative treatment with a Foley catheter, hyaluronic acid gel, and medication therapy. Hysteroscopy was repeated every 7 days after surgery. Multivariate regression analysis and propensity score matching (PSM) were performed to minimize intrinsic bias.ResultsA total of 212 patients with moderate to severe IUAs were included: 74 patients received 2 mg of estradiol valerate daily and 138 patients received 4 mg of estradiol daily postoperatively. No significant differences were found in the reproductive outcomes between the two groups, including clinical pregnancy rates. The multivariable regression analyses both before and after PSM also showed that there was no significant difference in the menstrual improvement and clinical pregnancy rates between the two groups.ConclusionsWe suggest the use of a lower dose (2 mg/day) of estradiol valerate as an adjuvant therapy for IUAs to minimize estrogen-related side effects.

Objective: This study aimed to investigate the differentiation of human adipose-derived stem cells (hASCs) into endometrial epithelial cells (EECs) under certain induction conditions and to a further step provide a promising approach for ASCs in clinical practice to the treatment of severe intrauterine adhesion. Methods: Four groups of hASCs were separately cultured as follows: in Group 1, hASCs were cultured in a control medium (5% fetal bovine serum [FBS] + α-minimum Eagle's medium [α-MEM]); in Group 2, hASCs were cultured in an induction medium (5% FBS + α-MEM + [1 × 10−7 mol/L 17β-estradiol] + 10 ng/mL transforming growth factor β1 [TGF-β1] + 10 ng/mL epidermal growth factor [EGF] + 10 ng/mL platelet-derived growth factor BB [PDGF-BB]); in Group 3, hASCs and human endometrium cells (hEMCs) were cocultured in the control medium; and in Group 4, hASCs and hEMCs were cocultured in the induction medium. Results: When cocultured with hEMCs, the morphology of hASCs became similar with EECs, and the addition of factors such as EGF, TGFβ, PDGF-BB, and 17β-estradiol promoted differentiation. This study, for the first time, demonstrated estrogen receptor (ER)α and ERβ expression in hASCs and preliminarily explored changes in ERα, ERβ, β-catenin, and H19 mRNA expression during hASC differentiation. Furthermore, we concluded that H19 mRNA expression was negatively correlated with differentiation, which is seemingly related to the estrogen signaling pathway. Conclusions: hASCs revealed the potential for differentiating to EECs when cocultured with hEMCs.

Antibodies are principal immune components elicited by vaccines to induce protection from microbial pathogens. In the Thai RV144 HIV-1 vaccine trial, vaccine efficacy was 31% and the sole primary correlate of reduced risk was shown to be vigorous antibody response targeting the V1V2 region of HIV-1 envelope. Antibodies against V3 also were inversely correlated with infection risk in subsets of vaccinees. Antibodies recognizing these regions, however, do not exhibit potent neutralizing activity. Therefore, we examined the antiviral potential of poorly neutralizing monoclonal antibodies (mAbs) against immunodominant V1V2 and V3 sites by passive administration of human mAbs to humanized mice engrafted with CD34+ hematopoietic stem cells, followed by mucosal challenge with an HIV-1 infectious molecular clone expressing the envelope of a tier 2 resistant HIV-1 strain. Treatment with anti-V1V2 mAb 2158 or anti-V3 mAb 2219 did not prevent infection, but V3 mAb 2219 displayed a superior potency compared to V1V2 mAb 2158 in reducing virus burden. While these mAbs had no or weak neutralizing activity and elicited undetectable levels of antibody-dependent cellular cytotoxicity (ADCC), V3 mAb 2219 displayed a greater capacity to bind virus- and cell-associated HIV-1 envelope and to mediate antibody-dependent cellular phagocytosis (ADCP) and C1q complement binding as compared to V1V2 mAb 2158. Mutations in the Fc region of 2219 diminished these effector activities in vitro and lessened virus control in humanized mice. These results demonstrate the importance of Fc functions other than ADCC for antibodies without potent neutralizing activity.

TiZrTaNb-based high-entropy alloys (HEAs) are research frontier of biomedical materials due to their high hardness, good yield strength, excellent wear resistance and corrosion resistance. Sn, as an essential trace element in the human body that plays a significant role in physiological process. It has stable chemical properties and a low elastic modulus. In this study, a new material, TiZrTaNbSn HEAs, was proposed as a potential biomedical alloy. The Ti35Zr25Ta15Nb15Sn10 biomedical high-entropy alloys (BHEAs) were successfully prepared through an arc melting furnace and then remelted using a German high-temperature and high-pressure apparatus under GPa-level (4 GPa and 7 GPa). The precipitation behavior of the needle-like HCP-Zr5Sn3 phase that precipitates discontinuously at the grain boundary was successfully controlled. The phase constitution, microstructure, and corrosion resistance of the alloy were studied. The results show that the needle-like HCP-Zr5Sn3 phase is eliminated and the (Zr, Sn)-rich nanoprecipitated phase is precipitated in the microstructure under high pressure, which leads to the narrowing of grain boundaries and consequently improves the corrosion resistance of the alloy. In addition, the formation mechanisms of (Zr, Sn)-rich nanoprecipitates in BHEAs were discussed. More Zr and Sn dissolve in the matrix due to the effect of high pressure, during the cooling process, they precipitate to form a (Zr, Sn)-rich nano-precipitated phase. [ABSTRACT FROM AUTHOR]

AIM: To evaluate the safety and efficacy of intravitreal etanercept in the inhibiting of proliferative vitreoretinopathy (PVR) in a model of penetrating ocular injury. METHODS: Penetrating ocular injury on the retina of rabbit was induced, which was subsequently treated using 0.1 mL of sterile water or 0.1 mL of 12.5 mg/mL etanercept. The development of PVR was evaluated by fundus images, the B-scan, and the histopathology. The mRNA and protein expressions of tumor necrosis factor-α (TNF-α), transforming growth factor β (TGF-β) as well as connective tissue growth factor (CTGF) were examined at various time points after the etanercept injection with the reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting, respectively. The safety of etanercept was evaluated by injection of 12.5 mg/mL etanercept into a normal rabbit eye without penetrating trauma. RESULTS: Clinical assessment and grading clearly demonstrated that the PVR formation was prevented in etanercept-treated animals, which was confirmed via fundus images, B-scan and histopathology. The RT-PCR and Western blotting showed increased mRNA and protein expression of TNF-α, TGF-β as well as CTGF in the retina of rabbits following penetrating ocular injury, and these factors were dramatically mitigated by ocular etanercept treatment. In addition, there was no adverse effect of etanercept intravitreal injection in normal eyes without penetrating trauma, it showed normal structure and histology. CONCLUSION: The etanercept is a potential therapy for inhibiting PVR development. To assess the clinic application of the etanercept in preventing PVR, further clinical studies are required.

C27H19NiN3O5, monoclinic, P21/c (no. 14), a = 11.082(1) Å, b = 10.480(1) Å, c = 22.719(2) Å, β = 117.76(4)°, V = 2334.9(9) Å3, Z = 4, Rgt(F) = 0.0489, wRref(F2) = 0.1271, T = 293 K. [ABSTRACT FROM AUTHOR]

A new alternative multi-scale calculation procedure was presented to characterize the time-dependent viscoelastic behaviors of resin-based three dimensional (3D) braided composites. The present investigation was processed based on micro-scale fiber/resin, meso-scale yarn/resin and macro-scale homogeneous composite. Integrating with the asymptotic expansion homogenization (AEH) method, the multi-scale physical fields in the three-scales is established, and the multi-phase finite element (MFE) method is adopted to overcome the difficulty in discretization for the heterogeneous structural models. The time-dependent stress relaxation responses under three-scales were particularly investigated by the coupling MFE-AEH multi-scale method. The time-dependent effective viscoelastic properties in the micro-sclae and meso-scale were also calculated by utilizing the Prony Series fitting to simplify the inverse Laplace transform. The accuracy and reliability are validated by the corresponding experimental and numerical results, the effects of braided angle and relaxation time on the viscoelastic properties of 3D braided composites were studied, respectively.

Background: Despite the great potential of utilizing human embryonic stem cells (hESCs)-derived cells as cell source for transplantation, these cells were often rejected during engraftment by the immune system due to adaptive immune response. Methods: We first evaluated HLA-G expression level in both hESCs and differentiated progenitor cells. After that, we generated modified hESC lines that over-express HLA-G1 using lentiviral infection with the construct contains both HLA-G1 and GFP tag. The lentivirus was first produced by co-transfecting HLA-G1 expressing lentiviral vector together with packaging vectors into packaging cell line 293T. Then the produced virus was used for the infection of selected hESC lines. We characterized the generated cell lines phenotype, including pluripotency and self-renewal abilities, as well as immune tolerance ability by mixed lymphocyte reaction (MLR) and cytotoxicity assays. Results: Although the hESCs do not express high levels of HLA-G1, over-expression of HLA-G1 in hESCs still retains their stem cell characteristics as determined by retaining the expression levels of OCT4 and SOX2, two critical transcriptional factors for stem cell function. Furthermore, the HLA-G1 overexpressing hESCs retain the self-renewal and pluripotency characteristics of stem cells, which can differentiate into different types of cells, including pigment cells, smooth muscle cells, epithelia-like cells, and NPCs. After differentiation, the differentiated cells including NPCs retain the high levels of HLA-G1 protein. In comparison with conventional NPCs, these HLA-G1 positive NPCs have enhanced immune tolerance ability. Conclusions: Ectopic expression of HLA-G1, a non-classical major histocompatibility complex class I (MHC I) antigen that was originally discovered involving in engraftment tolerance during pregnancy, can enhance the immunological tolerance in differentiated neural progenitor cells (NPCs). Our study shows that stably overexpressing HLA-G1 in hESCs might be a feasible strategy for enhancing the engraftment of NPCs during transplantation.