Molecular and physiological changes in the SpaceX Inspiration4 civilian crew.

Human spaceflight has historically been managed by government agencies, such as in the NASA Twins Study1, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first all-civilian crew to low Earth orbit, which included the youngest American astronaut (aged 29), new in-flight experimental technologies (handheld ultrasound imaging, smartwatch wearables and immune profiling), ocular alignment measurements and new protocols for in-depth, multi-omic molecular and cellular profiling. Here we report the primary findings from the 3-day spaceflight mission, which induced a broad range of physiological and stress responses, neurovestibular changes indexed by ocular misalignment, and altered neurocognitive functioning, some of which match those of long-term spaceflight2, but almost all of which did not differ from baseline (pre-flight) after return to Earth. Overall, these preliminary civilian spaceflight data suggest that short-duration missions do not pose a significant health risk, and moreover present a rich opportunity to measure the earliest phases of adaptation to spaceflight in the human body at anatomical, cellular, physiological and cognitive levels. Finally, these methods and results lay the foundation for an open, rapidly expanding biomedical database for astronauts3, which can inform countermeasure development for both private and government-sponsored space missions.

Targeting the metabolism of tumor-infiltrating regulatory T cells.

Although targeting the tumor metabolism is performed in cooperation with immunotherapy in the era of precision oncology, ignorance of immune cells' metabolism has resulted in unstable antitumor responses. Tumor-infiltrating regulatory T cells (TI-Tregs) are unique, overcoming the hypoxic, acidic, and nutrient-deficient tumor microenvironments (TMEs) and maintaining immunosuppressive functions. However, secondary autoimmunity caused by systemic Treg depletion remains the 'Sword of Damocles' for current Treg-targeted therapies. In this opinion piece, we propose that metabolically reprogrammed TI-Tregs might represent an obstacle to cancer therapies. Indeed, metabolism-based Treg-targeted therapy might provide higher selectivity for clearing TI-Tregs than traditional kinase/checkpoint inhibitors and chemokine/chemokine receptor blockade; it might also restore the efficacy of targeting the tumor metabolism and eliminate certain metabolic barriers to immunotherapy.

Genome-wide association study identifies high-impact susceptibility loci for HCC in North America.

BACKGROUND AND AIMS: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). APPROACH AND RESULTS: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40-0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62-0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29-1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33-1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51-1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74-0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. CONCLUSIONS: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.

Molecular O2 Dimers and Lattice Instability in a Perovskite Electrocatalyst.

Structural degradation of oxide electrodes during the electrocatalytic oxygen evolution reaction (OER) is a major challenge in water electrolysis. Although the OER is known to induce changes in the surface layer, little is known about its effect on the bulk of the electrocatalyst and its overall phase stability. Here, we show that under OER conditions, a highly active SrCoO3-x electrocatalyst develops bulk lattice instability, which results in the formation of molecular O2 dimers inside the bulk and nanoscale amorphization induced via chemo-mechanical coupling. Using high-resolution resonant inelastic X-ray scattering and first-principles calculations, we unveil the potential-dependent evolution of lattice oxygen inside the perovskite and demonstrate that O2 dimers are stable in a densely packed crystal lattice, thus challenging the assumption that O2 dimers require sufficient interatomic spacing. We also show that the energy cost of local atomic rearrangements in SrCoO3-x becomes very low under the OER conditions, leading to an unusual amorphization under intercalation-induced stress. As a result, we propose that the amorphization energy can be calculated from the first principles and can be used to assess the stability of electrocatalysts. Our study demonstrates that extreme oxidation of electrocatalysts under OER can intrinsically destabilize the lattice and result in bulk anion redox and disorder, suggesting why some oxide materials are unstable and develop a thick amorphous layer under water electrolysis conditions.

A west African ancestry-associated SNP on 8q24 predicts a positive biopsy in African American men with suspected prostate cancer following PSA screening.

BACKGROUND: African American (AA) men have the highest incidence and mortality rates of prostate cancer (PCa) among all racial groups in the United States. While race is a social construct, for AA men, this overlaps with west African ancestry. Many of the PCa susceptibility variants exhibit distinct allele frequencies and risk estimates across different races and contribute substantially to the large disparities of PCa incidence among races. We previously reported that a single-nucleotide polymorphism (SNP) in 8q24, rs7824364, was strongly associated with west African ancestry and increased risks of PCa in both AA and Puerto Rican men. In this study, we determined whether this SNP can predict biopsy positivity and detection of clinically significant disease (Gleason score [GS] ≥ 7) in a cohort of AA men with suspected PCa. METHODS: SNP rs7824364 was genotyped in 199 AA men with elevated total prostate-specific antigen (PSA) (>2.5 ng/mL) or abnormal digital rectal exam (DRE) and the associations of different genotypes with biopsy positivity and clinically significant disease were analyzed. RESULTS: The variant allele carriers were significantly over-represented in the biopsy-positive group compared to the biopsy-negative group (44% vs. 25.7%, p = 0.011). In the multivariate logistic regression analyses, variant allele carriers were at a more than a twofold increased risk of a positive biopsy (odds ratio [OR] = 2.14, 95% confidence interval [CI] = 1.06-4.32). Moreover, the variant allele was a predictor (OR = 2.26, 95% CI = 1.06-4.84) of a positive biopsy in the subgroup of patients with PSA < 10 ng/mL and normal DRE. The variant allele carriers were also more prevalent in cases with GS ≥ 7 compared to cases with GS < 7 and benign biopsy. CONCLUSIONS: This study demonstrated that the west African ancestry-specific SNP rs7824364 on 8q24 independently predicted a positive prostate biopsy in AA men who were candidates for prostate biopsy subsequent to PCa screening.

Two Birds with One Stone: Contemporaneously Enhancing OER Catalytic Activity and Stability for Dual-Phase Medium-Entropy Metal Sulfides.

Transition metal-based sulfides exhibit remarkable potential as electrocatalysts for oxygen evolution reaction (OER) due to the unique intrinsic structure and physicochemical characteristics. Nevertheless, currently available sulfide catalysts based on transition metals face a bottleneck in large-scale commercial applications owing to their unsatisfactory stability. Here, the first fabrication of (FeCoNiMn2 )S2 dual-phase medium-entropy metal sulfide (dp-MEMS) is successfully achieved, which demonstrated the expected optimization of stability in the OER process. Benefiting from the "cell wall" -like structure and the synergistic effect in medium-entropy systems, (FeCoNiMn2 )S2 dp-MEMS delivers an exceptionally low overpotential of 169 and 232 mV at current densities of 10 and 100 mA cm-2 , respectively. The enhancement mechanism of catalytic activity and stability is further validated by density functional theory (DFT) calculations. Additionally, the rechargeable Zn-air batteries integrated with FeCoNiMn2 )S2 dp-MEMS exhibit remarkable performance outperforming the commercial catalyst (Pt/C+RuO2 ). This work demonstrates that the dual-phase medium-entropy metal sulfide-based catalysts have the potential to provide a greater application value for OER and related energy conversion systems.

Efficacy and safety of immunosuppressants and monoclonal antibodies in adults with myasthenia gravis: a systematic review and network meta-analysis.

Numerous clinical trials for myasthenia gravis (MG) treatment have been conducted recently, with satisfactory cognitive and clinical results. However, due to the limited evidence for direct comparison of the safety and effectiveness of various drugs, there is a need for further exploration of the advantages and disadvantages of different monoclonal antibodies and immunosuppressants. Thus, in the present network meta-analysis (NMA), we aimed to compare the efficacy and safety of immunosuppressants and monoclonal antibodies in treating MG. We systematically searched for randomized controlled trials published in PubMed, Embase, Web of Science, and the Cochrane Library between January 1, 2000 and March 6, 2024. Statistical analyses were performed using R software (version 4.2.3), JAGS, and STATA (version 15.0). The surface under the cumulative ranking curve (SUCRA) value was calculated to assess the potential efficacy of each drug and the likelihood of adverse events (AEs), with higher SUCRA values indicating better efficacy or a lower likelihood of AEs. This NMA included 21 randomized controlled trials involving 13 drugs and 1,657 patients. Based on changes in Quantitative MG and MG Composite scores, batoclimab was most likely to exert the best therapeutic effects, with SUCRA values of 99% and 92%, respectively. Rozanolixzumab performed better than the other drugs in terms of the MG Activities of Daily Living score (85%). Eculizumab exhibited the highest potential in reducing the 15-item revised version of the MG Quality of Life score (96%). Regarding safety, belimumab had the highest SUCRA value (85%), demonstrating the lowest likelihood of AEs. In conclusion, all immunosuppressants and monoclonal antibodies analyzed in this study were more effective than the placebo in treating MG, with rozanolixzumab and batoclimab potentially being the most effective. Regarding safety, rozanolixzumab exhibited a higher likelihood of AEs than did placebo. The conclusions guide the clinical selection of effective drugs and offer insights for future drug experiments.

Clinical Characteristics and Prognosis of Heart Failure with Preserved Ejection Fraction Across Diverse Ejection Fraction Ranges.

Background: Recent studies have indicated that heart failure (HF) with preserved ejection fraction (HFpEF) within different left ventricular ejection fraction (LVEF) ranges presents distinct morphological and pathophysiological characteristics, potentially leading to diverse prognoses. Methods: We included chronic HF patients hospitalized in the Department of Cardiology at Hebei General Hospital from January 2018 to June 2021. Patients were categorized into four groups based on LVEF: HF with reduced ejection fraction (HFrEF, LVEF ≤ 40%), HF with mildly reduced ejection fraction (HFmrEF, 41% ≤ LVEF ≤ 49%), low LVEF-HFpEF (50% ≤ LVEF ≤ 60%), and high LVEF-HFpEF (LVEF > 60%). Kaplan‒Meier curves were plotted to observe the occurrence rate of endpoint events (all-cause mortality and cardiovascular mortality) within a 2-year period. Cox proportional hazards regression models were employed to predict the risk factors for endpoint events. Sensitivity analyses were conducted using propensity score matching (PSM), and Fine-Gray tests were used to evaluate competitive risk. Results: A total of 483 chronic HF patients were ultimately included. Kaplan‒Meier curves indicated a lower risk of endpoint events in the high LVEF-HFpEF group than in the low LVEF-HFpEF group. After PSM, there were still statistically significant differences in endpoint events between the two groups (all-cause mortality p = 0.048, cardiovascular mortality p = 0.027). Body mass index (BMI), coronary artery disease, cerebrovascular disease, hyperlipidemia, hypoalbuminemia, and diuretic use were identified as independent risk factors for all-cause mortality in the low LVEF-HFpEF group (p < 0.05). Hyperlipidemia, the estimated glomerular filtration rate (eGFR), and ß -blocker use were independent risk factors for cardiovascular mortality (p < 0.05). In the high LVEF-HFpEF group, multivariate Cox regression analysis revealed that age, smoking history, hypoalbuminemia, and the eGFR were independent risk factors for all-cause mortality, while age, heart rate, blood potassium level, and the eGFR were independent risk factors for cardiovascular mortality (p < 0.05). After controlling for competitive risk, cardiovascular mortality risk remained higher in the low LVEF-HFpEF group than in the high LVEF-HFpEF group (Fine-Gray p < 0.01). Conclusions: Low LVEF-HFpEF and high LVEF-HFpEF represent two distinct phenotypes of HFpEF. Patients with high LVEF-HFpEF have lower risks of both all-cause mortality and cardiovascular mortality than those with low LVEF-HFpEF. The therapeutic reduction in blood volume may not be the best treatment option for patients with high LVEF-HFpEF.

miR-455/GREM1 axis promotes colorectal cancer progression and liver metastasis by affecting PI3K/AKT pathway and inducing M2 macrophage polarization.

BACKGROUND: Colorectal cancer is among the most common malignant tumors affecting the gastrointestinal tract. Liver metastases, a complication present in approximately 50% of colorectal cancer patients, are a considerable concern. Recently, studies have revealed the crucial role of miR-455 in tumor pathogenesis. However, the effect of miR-455 on the progression of liver metastases in colorectal cancer remains controversial. As an antagonist of bone morphogenetic protein(BMP), Gremlin 1 (GREM1) may impact organogenesis, body patterning, and tissue differentiation. Nevertheless, the role of miR-455 in regulating GREM1 in colorectal cancer liver metastases and how miR-455/GREM1 axis influences tumour immune microenvironment is unclear. METHODS: Bioinformatics analysis shows that miR-455/GREM1 axis plays crucial role in liver metastasis of intestinal cancer and predicts its possible mechanism. To investigate the impact of miR-455/GREM1 axis on the proliferation, invasion, and migration of colorectal cancer cells, colony formation assay, wound healing and transwell assay were examined in vitro. The Dual-Luciferase reporter gene assay and RNA pull-down assay confirmed a possible regulatory effect between miR-455 and GREM1. In vivo, colorectal cancer liver metastasis(CRLM) model mice was established to inquiry the effect of miR-455/GREM1 axis on tumor growth and macrophage polarization. The marker of macrophage polarization was tested using immunofluorescence(IF) and quantitative real-time polymerase chain reaction(qRT-PCR). By enzyme-linked immunosorbent assay (ELISA), cytokines were detected in culture medium supernatants. RESULTS: We found that miR-455 and BMP6 expression was increased and GREM1 expression was decreased in liver metastase compared with primary tumor. miR-455/GREM1 axis promotes colorectal cancer cells proliferation, migration, invasion via affected PI3K/AKT pathway. Moreover, downregulating GREM1 augmented BMP6 expression in MC38 cell lines, inducing M2 polarization of macrophages, and promoting liver metastasis growth in CRLM model mice. CONCLUSION: These data suggest that miR-455/GREM1 axis promotes colorectal cancer progression and liver metastasis by affecting PI3K/AKT pathway and inducing M2 macrophage polarization. These results offer valuable insights and direction for future research and treatment of CRLM.

A modified CEUS risk stratification model for adnexal masses with solid components: prospective multicenter study and risk adjustment.

OBJECTIVES: To evaluate the additional advantages of integrating contrast-enhanced ultrasound (CEUS) into the Ovarian-Adnexal Reporting and Data System (O-RADS) ultrasound (US) for the characterization of adnexal lesions with solid components. MATERIALS AND METHODS: This prospective multicenter study recruited women suspected of having adnexal lesions with solid components between September 2021 and December 2022. All patients scheduled for surgery underwent preoperative CEUS and US examinations. The lesions were categorized according to the O-RADS US system, and quantitative CEUS indexes were recorded. Pathological results served as the reference standard. Univariable and multivariable analyses were performed to identify risk factors for malignancy in adnexal lesions with solid components. Receiver operating characteristic (ROC) curve analysis was employed to assess diagnostic performance. RESULTS: A total of 180 lesions in 175 women were included in the study. Among these masses, 80 were malignant and 100 were benign. Multivariable analysis revealed that serum CA-125, the presence of acoustic shadowing, and peak intensity (PI) ratio (PImass/PIuterus) of solid components on CEUS were independently associated with adnexal malignancy. The modified CEUS risk stratification model demonstrated superior diagnostic value in assessing adnexal lesions with solid components compared to O-RADS US (AUC: 0.91 vs 0.78, p < 0.001) and exhibited comparable performance to the Assessment of Different NEoplasias in the adnexa (ADNEX) model (AUC 0.91 vs 0.86, p = 0.07). CONCLUSION: Our findings underscore the potential value of CEUS as an adjunctive tool for enhancing the precision of diagnostic evaluations of O-RADS US. CLINICAL RELEVANCE STATEMENT: The promising performance of the modified CEUS risk stratification model suggests its potential to mitigate unnecessary surgeries in the characterization of adnexal lesions with solid components. KEY POINTS: • The additional value of CEUS to O-RADS US in distinguishing between benign and malignant adnexal lesions with solid components requires further evaluation. • The modified CEUS risk stratification model displayed superior diagnostic value and specificity in characterizing adnexal lesions with solid components when compared to O-RADS US. • The inclusion of CEUS demonstrated potential in reducing the need for unnecessary surgeries in the characterization of adnexal lesions with solid components.

NiO/RuO2 p-n Heterojunction Nanofoam as a High-Performance Electrocatalyst for Desulfurization and Concurrent Hydrogen Evolution.

The development of bifunctional electrocatalysts with excellent performance in both the hydrogen evolution reaction (HER) and sulfide oxidation reaction (SOR) remains a formidable challenge. Herein, we experimentally synthesize a NiO/RuO2 p-n heterojunction nanofoam that exhibits highly desirable electrocatalytic properties for both the HER and the SOR. We further design an electrolytic cell by pairing alkaline HER with SOR utilizing the NiO/RuO2 heterojunction nanofoam as both the anode and the cathode, which demands a low applied voltage of 0.846 V to achieve a current density of 10 mA cm-2. Density functional theory calculations confirm that the formation of the NiO/RuO2 p-n heterojunction nanofoam effectively regulates the electronic structure, thereby boosting the electrocatalytic performances for both HER and SOR. This work not only provides a novel strategy to prepare an efficient and stable nanofoam electrocatalyst for hydrogen production but also highlights the potential application of oxide heterojunction electrocatalysts in treating sulfur-containing waste liquid.

Development of an AIE-active fluorescent probe for the simultaneous detection of Al3+ and viscosity and imaging in Alzheimer's disease model.

Alzheimer's disease is associated both with imbalances in Al3+ production and changes in viscosity in cells. Their simultaneous measurement could therefore provide valuable insights into Alzheimer's disease pathology. Their simultaneous measurement would therefore be of great value in investigating the pathological mechanism of Alzheimer's disease. We designed a fluorescent probe YM2T with AIE effect that is capable of selectively responding to Al3+ by fluorescence colormetrics and to viscosity by fluorescence "turn on" modes. Additionally, Al3+ and viscosity were simultaneously detected in PC12 cells using the low cytotoxic probe YM2T via blue and green fluorescence channels. More importantly, the YM2T probe was used to image mice with AD. Hence, the YM2T probe shows potential as a useful molecular instrument for studying the pathological impact of Al3+ and viscosity.

The multiple mediation model of social support and postpartum anxiety symptomatology: the role of resilience, postpartum stress, and sleep problems.

OBJECTIVE: This study aimed to assess the prevalence of postpartum anxiety and the factors influencing it, while also exploring the multiple mediating roles of related factors between social support and postpartum anxiety symptomatology among postpartum women in China. METHODS: Between April and August 2023, we recruited a total of 824 postpartum women through a convenience sampling method. These participants completed a series of general survey questionnaires and were evaluated using the depression anxiety stress scale, perceived social support scale, 10-item Connor-Davidson resilience scale, maternal postpartum stress scale, and Pittsburgh sleep quality index. Additionally, we employed a hierarchical multiple regression model to investigate the relevant factors and mediators of postpartum anxiety symptomatology. A structural equation model was used to examine the mediating role of resilience, postpartum stress, and sleep problems in the relationship between social support and postpartum anxiety symptomatology. RESULTS: Our study found a postpartum anxiety symptomatology prevalence rate of 18.40%. The factors influencing postpartum anxiety symptomatology included age, education of their husband, mastitis, social support, resilience, postpartum stress, and sleep problems. Through a multiple mediation analysis, we found that resilience, postpartum stress, and sleep problems completely mediated the effects of social support on postpartum anxiety symptomatology, with the mediating effect accounting for 83.57% of the total effect. CONCLUSION: The multiple mediation analysis revealed that among postpartum women, the impact of social support on postpartum anxiety symptomatology is channeled through resilience, postpartum stress, and sleep problems. Therefore, enhancing social support, resilience, postpartum stress, and sleep problems might alleviate postpartum anxiety symptomatology.

Nonlinear error analysis of fast optical delay lines.

Optical delay lines have wide applications in terahertz time-domain spectroscopy and optical coherence tomography. In this study, a fast-rotating optical delay line (FRODL) with 24 turntable reflection surfaces was designed. By analyzing the working principle of the FRODL, a mathematical model was established for the nonlinear parameter error of the FRODL delay time. By constructing the polarization Michelson interference system and testing the FRODL structure, the error of actual assembly parameters of the FRODL was approximately 0.015 mm, the actual delay time of the FRODL was greater than 43.5 ps, and the linearity was 99.785%.

TRAF6 directs FOXP3 localization and facilitates regulatory T-cell function through K63-linked ubiquitination.

Regulatory T cells (Tregs) are crucial mediators of immune control. The characteristic gene expression and suppressive functions of Tregs depend considerably on the stable expression and activity of the transcription factor FOXP3. Transcriptional regulation of the Foxp3 gene has been studied in depth, but both the expression and function of this factor are also modulated at the protein level. However, the molecular players involved in posttranslational FOXP3 regulation are just beginning to be elucidated. Here, we found that TRAF6-deficient Tregs were dysfunctional in vivo; mice with Treg-restricted deletion of TRAF6 were resistant to implanted tumors and displayed enhanced anti-tumor immunity. We further determined that FOXP3 undergoes K63-linked ubiquitination at lysine 262 mediated by the E3 ligase TRAF6. In the absence of TRAF6 activity or upon mutation of the ubiquitination site, FOXP3 displayed aberrant, perinuclear accumulation and disrupted regulatory function. Thus, K63-linked ubiquitination by TRAF6 ensures proper localization of FOXP3 and facilitates the transcription factor's gene-regulating activity in Tregs. These results implicate TRAF6 as a key posttranslational, Treg-stabilizing regulator that may be targeted in novel tolerance-breaking therapies.

Human Cytomegalovirus Hijacks WD Repeat Domain 11 for Virion Assembly Compartment Formation and Virion Morphogenesis.

Human cytomegalovirus (HCMV) has a large (∼235 kb) genome with more than 200 predicted open reading frames that exploits numerous cellular factors to facilitate its replication. A key feature of HCMV-infected cells is the emergence of a distinctive membranous cytoplasmic compartment termed the virion assembly compartment (vAC). Here, we report that host protein WD repeat domain 11 (WDR11) plays a key role in vAC formation and virion morphogenesis. We found that WDR11 was upregulated at both mRNA and protein levels during HCMV infection. At the late stage of HCMV replication, WDR11 relocated to the vAC and colocalized with markers of the trans-Golgi network (TGN) and vAC. Depletion of WDR11 hindered HCMV-induced membrane reorganization of the Golgi and TGN, altered vAC formation, and impaired HCMV secondary envelopment and virion morphogenesis. Further, motifs critical for the localization of WDR11 in TGN were identified by alanine-scanning mutagenesis. Mutation of these motifs led to WDR11 mislocation outside the TGN and loss of vAC formation. Taken together, these data indicate that host protein WDR11 is required for efficient viral replication at the stage of virion assembly, possibly by facilitating the remodeling of the endomembrane system for vAC formation and virion morphogenesis. IMPORTANCE During the late phase of human cytomegalovirus (HCMV) infection, the endomembrane system is dramatically reorganized, resulting in the formation of a unique structure termed the virion assembly compartment (vAC), which is critical for the assembly of infectious virions. The mechanism of HCMV-induced vAC formation is still not fully understood. In this report, we identified a host factor, WDR11, that plays an important role in vAC formation. Our findings argue that WDR11 contributes to the relocation of the Golgi and trans-Golgi network to the vAC, a membrane reorganization process that appears to be required for efficient virion maturation. The present work provides new insights into the vAC formation and HCMV virion morphogenesis and a potential novel target for antiviral treatment.

The mediating role of social support and resilience between self-efficacy and prenatal stress: a mediational analysis.

BACKGROUND: Prenatal stress is a highly prevalent mental disorder experienced by pregnant women. This study assessed the prevalence and influencing factors of prenatal stress and investigated the mediating role of social support and resilience between self-efficacy and prenatal stress among pregnant women in China. METHODS: A convenience sample comprising 1071 pregnant women from three hospitals in Nantong, Jiangsu Province, China, was recruited between February and June 2023. These participants completed a set of general survey questionnaires and were assessed using the Pregnancy Pressure Scale, Perceived Social Support Scale, the 10-item Connor-Davidson Resilience Scale, and the Chinese version of the General Self-Efficacy Scale. Furthermore, a hierarchical multiple regression model was employed to investigate the relevant factors and mediators of prenatal stress symptoms. A structural equation model was used to examine the mediating role of social support and resilience in the relationship between self-efficacy and prenatal stress. RESULTS: The results of the multivariate regression analysis indicated significant associations between prenatal stress and parity, self-efficacy, social support, and resilience (P < 0.001). Self-efficacy accounted for 35.33% of the total effect, with a direct effect of -2.5306 (95% confidence interval [CI]: -4.0309 to -1,0303). Further examination through mediation analysis revealed the mediating roles of social support and resilience in the relationship between self-efficacy and prenatal stress. The mediating effect of social support was - 1.5933 (95% CI: -2.2907 to -0.9496), accounting for 22.24% of the total effect. Similarly, resilience exhibited a mediating effect of -3.0388 (95% CI: -4.3844 to -1.7135), accounting for 42.43% of the total effect. CONCLUSION: The mediation analysis revealed that among pregnant women in China, the influence of self-efficacy on prenatal stress is channelled through social support and resilience. Therefore, enhancing social support, resilience, and self-efficacy might alleviate prenatal stress.

The effect of perceived social support on postpartum stress: the mediating roles of marital satisfaction and maternal postnatal attachment.

BACKGROUND: Multiple factors may be responsible for the development of postpartum stress, including perceived social support, marital satisfaction, and maternal postnatal attachment. However, the underlying mediation mechanisms remain unclear. This study examined the complex relationships between perceived social support and postpartum stress among Chinese women. METHODS: A convenience sample comprising 406 postpartum women was recruited from six hospitals in Nantong, Jiangsu Province, China. The participants completed general survey questionnaires and were evaluated using the Maternal Postpartum Stress Scale, the Perceived Social Support Scale, the Maternal Postnatal Attachment Scale, and the Marital Satisfaction Scale. Furthermore, we evaluated the relationship between postpartum stress and the various influencing factors by performing a multiple linear regression analysis. The potential mediating roles of marital satisfaction and maternal and infant attachment in the association between perceived social support and postpartum stress were explored by performing a mediation analysis. RESULTS: According to the multivariate regression analysis, perceived social support, marital satisfaction, and maternal postnatal attachment contributed to postpartum stress levels (P < 0.05). The mediation analysis revealed that marital satisfaction and maternal postnatal attachment played parallel mediating roles in the association between perceived social support and postpartum stress, and the mediating effect of marital satisfaction was - 0.1125 (95% confidence interval [CI]: -0.1784 to -0.0520), accounting for 33.20% of the total effect, and the mediating effect of maternal postnatal attachment was - 0.0847 (95% CI: -0.1304 to -0.0438), accounting for 25.00% of the total effect. CONCLUSION: Our study revealed that perceived social support could influence postpartum stress not only through direct effect (41.80% of the total effect), but also through the indirect effect (mediation effect) of marital satisfaction and maternal postnatal attachment (58.20% of the total effect), suggesting that improving postpartum women's social support, enhancing maternal and infant attachment, and improving their marital satisfaction could help lower postpartum stress.

Au nano-cone array for SERS detection of associated miRNA in lymphoma patients.

Based on Au nano-cone array (Au-NCA) and a three-segment hybridization strategy, a novel SERS biosensor is proposed for the ultrasensitive detection of the microRNA miR-21. The uniform, stable, and reproducible Au-NCA was prepared by the single-layer colloidal ball template method. Subsequently, the target was hybridized with sequence 2. The resulting target-sequence 2 complex was then hybridized with sequence 1 anchored on Au-NCA. Thus, a three-segment sequence complex was formed. SERS measurements can be performed without the need for complex purification and amplification steps. Due to the ability of miR-21 to perform specific complementary hybridization with two sequences, SERS biosensors have superior specificity for miR-21 without interference from other miRNAs. Under the optimal conditions, the SERS biosensor was applied and the limit of detection (LOD) was as low as 3.02 aM. This method has been successfully used to the detection of miR-21 in the serum of lymphoma patients and healthy volunteers. The results are consistent with the traditional test methods. Therefore, this novel SERS biosensor shows excellent clinical translational potential in the detection of lymphoma.

Chemical fingerprint analysis and quality assessment of Tibetan medicine Triphala from different origins by high-performance liquid chromatography.

INTRODUCTION: Although the Tibetan medicine Triphala (THL) is widely used in many countries, insufficient progress has been made in quality control. OBJECTIVES: The present study aimed to propose a methodology for quality control of THL based on HPLC fingerprinting combined with an orthogonal array design. METHODS: Seven identified peaks were used as indicators to examine the effects of temperature, extraction time, and solid-liquid ratio on the dissolution of active ingredients in THL. Fingerprint analysis was performed on 20 batches of THL from four geographical areas (China, Laos, Thailand, and Vietnam). For further chemometric assessment, analysis techniques including similarity analysis, hierarchical clustering analysis, principal component analysis, and orthogonal partial least squares discrimination analysis (OPLS-DA) were used to classify the 20 batches of samples. RESULTS: Fingerprints were established and 19 common peaks were identified. The similarity of 20 batches of THL was more than 0.9 and the batches were divided into two clusters. Four differential components of THL were identified based on OPLS-DA, including chebulinic acid, chebulagic acid, and corilagin. The optimal extraction conditions were an extraction time of 30 min, a temperature of 90°C, and a solid-liquid ratio of 30 mL/g. CONCLUSION: HPLC fingerprinting combined with an orthogonal array design could be used for comprehensive evaluation and quality assessment of THL, providing a theoretical basis for further development and utilization of THL.