Revealing the Mechanisms of Qilongtian Capsules in the Treatment of Chronic Obstructive Pulmonary Disease Based on Integrated Network Pharmacology, Molecular Docking, and In Vivo Experiments.

The Qilongtian capsule (QLT) is a Chinese patent medicine that has been approved for the treatment of chronic obstructive pulmonary disease (COPD). However, the precise pharmacodynamic material basis and molecular mechanism have not been well illustrated. In this study, we identified the effect of QLT on COPD through a cigarette smoke extract (CSE)/lipopolysaccharide (LPS) induced COPD mice model. The absorption of blood components in QLT were identified using ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Network pharmacology was used to predict the potential targets and therapeutic mechanisms of QLT, which were further validated using in vivo experiments and molecular docking. Pharmacodynamic studies revealed that QLT could ameliorate pulmonary function and pulmonary pathology, reduce collagen fiber accumulation, and attenuate inflammatory responses in mice with CSE/LPS induced COPD. A total of 21 components of QLT absorbed in the blood were detected. Network pharmacology analysis indicated that TNF, IL-6, EGFR, and AKT1 may be the core targets, mainly involving the MAPK signaling pathway. Besides, Sachaloside II, Ginsenoside Rh1, Ginsenoside F1, Rosiridin, and Ginsenoside Rf were the key compounds. Molecular docking results showed that the key components could spontaneously bind to EGFR and MAPK to form a relatively stable conformation. In vivo experiments revealed that QLT could suppress the activation of the EGFR/MAPK signaling pathway, thereby improving lung injury in mice with COPD. Overall, these findings provide evidence for the treatment of COPD with QLT.

Exploring the Molecular Mechanisms of Herbs in the Treatment of Hyperlipidemia Based on Network Pharmacology and Molecular Docking.

Many herbs have been shown to safely and successfully treat hyperlipidemia. However, the molecular mechanisms underlying their treatment remain unclear. In this study, 103 prescriptions for the treatment of hyperlipidemia containing 146 herbs were screened. Cluster analyses identified a core prescription comprising five herbs, namely, Crataegus pinnatifida (Shan Zha), Cassiae semen (Jue Ming Zi), Alisma orientale (Sam.) Juz. (Ze Xie), Salvia miltiorrhiza (Dan Shen), and Radix Polygoni Multiflori (He Shou Wu), in combination for the treatment of hyperlipidemia. Next, 9, 62, 5, 132, and 34 potential targets for each of the core herbs and a total of 512 hyperlipidemia-related protein targets were detected. Finally, 40 targets shared by core herbs and hyperlipidemia were identified. IL6, AKT1, IL1B, PTGS2, VEGFA, PPARG, and NOS3 were the seven proteins that were found to be most important in the treatment of hyperlipidemia. Interestingly, the Kyoto Encyclopedia of Genes and Genomes pathway indicated that these targets were mainly enriched in the lipid and atherosclerosis pathway and the cancer pathway. In addition, core target proteins such as AKT1, PTGS2, and PPARG have been demonstrated to play critical roles in hyperlipidemia and pancreatic cancer. Significant affinity between bioactive chemicals and proteins involved in cancer pathways was found by molecular docking. Molecular docking results showed that AKT1, PTGS2, and PPARG exhibited good binding ability with three bioactive chemicals, including 3-beta-hydroxymethyllenetanshiquinone, danshexinkum d, and physciondiglucoside. The treatment of hyperlipidemia by herbs may be mediated through the modulation of proteins associated with the cancer pathway. This study helps to provide a theoretical basis for future combined therapy for hyperlipidemia and cancer. [Figure: see text].

Molecular-level insights into the brewing-dependent chemical diversity, properties, and formation mechanism of Moutai Base baijiu using Fourier transform ion cyclotron resonance mass spectrometry.

The brewing-dependent molecular diversity, properties, and formation mechanism of Moutai (a typical sauce-flavor Baijiu) base Baijiu, were explored using FT-ICR MS combined with various visualization methods. Seven-round Moutai base Baijiu exhibited significant diversity and heterogeneity, containing more unsaturated/saturated reduced molecules. The increased brewing round increased the molecular unsaturation/aromaticity and enhanced the transformation between saturated/oxidized and unsaturated/reduced molecules. Moreover, lignin-/aliphatic-/peptide-/lipid-like molecules dominated the molecular characteristics of Moutai base Baijiu. The basic and acidic components contained more reduced carbohydrate-/lipid-like molecules and oxidized tannin-like/condensed aromatic molecules, respectively, contributing to the molecular stability and diversity, respectively. More unique lipid-like and lignin-like molecules newly formed in the early and late brewing rounds, respectively, and the increased brewing shifted the chemical reaction from a single dominant to a multi-dimensional balance. More unique N-containing molecules (>450 Da) significantly contributed the specific brewing characteristics. These new findings help to understand the molecular-level formation mechanism of Moutai base Baijiu.

Application of Machine Learning in Nanotoxicology: A Critical Review and Perspective.

The massive production and application of nanomaterials (NMs) have raised concerns about the potential adverse effects of NMs on human health and the environment. Evaluating the adverse effects of NMs by laboratory methods is expensive, time-consuming, and often fails to keep pace with the invention of new materials. Therefore, in silico methods that utilize machine learning techniques to predict the toxicity potentials of NMs are a promising alternative approach if regulatory confidence in them can be enhanced. Previous reviews and regulatory OECD guidance documents have discussed in detail how to build an in silico predictive model for NMs. Nevertheless, there is still room for improvement in addressing the ways to enhance the model representativeness and performance from different angles, such as data set curation, descriptor selection, task type (classification/regression), algorithm choice, and model evaluation (internal and external validation, applicability domain, and mechanistic interpretation, which is key to ensuring stakeholder confidence). This review explores how to build better predictive models; the current state of the art is analyzed via a statistical evaluation of literature, while the challenges faced and future perspectives are summarized. Moreover, a recommended workflow and best practices are provided to help in developing more predictive, reliable, and interpretable models that can assist risk assessment as well as safe-by-design development of NMs.

A highly stretchable smart dressing for wound infection monitoring and treatment.

Smart dressings integrated with bioelectronics have attracted considerable attention and become promising solutions for skin wound management. However, due to the mechanical distinction between human body and the interface of electronics, previous smart dressings often suffered obvious degradation in electrical performance when attached to the soft and curvilinear wound sites. Here, we report a stretchable dressing integrated with temperature and pH sensor for wound status monitoring, as well as an electrically controlled drug delivery system for infection treatment. The wound dressing was featured with the deployment of liquid metal for seamless connection between rigid electrical components and gold particle-based electrodes, achieving a stretchable soft-hard interface. Stretching tests showed that both the sensing system and drug delivery system exhibited good stretchability and long-term stable conductivity with the resistance change rate less than 6 % under 50 % strain. Animal experiments demonstrated that the smart dressing was capable of detecting bacterial infection via the biomarkers of temperature and pH value and the infection factors of wound were significantly improved with therapy through electrically controlled antibiotics releasing. This proof-of-concept prototype has potential to significantly improve management of the wound, especially those with dynamic strain.

Vertically stacked skin-like active-matrix display with ultrahigh aperture ratio.

Vertically stacked all-organic active-matrix organic light-emitting diodes are promising candidates for high-quality skin-like displays due to their high aperture ratio, extreme mechanical flexibility, and low-temperature processing ability. However, these displays suffer from process interferences when interconnecting functional layers made of all-organic materials. To overcome this challenge, we present an innovative integration strategy called "discrete preparation-multilayer lamination" based on microelectronic processes. In this strategy, each functional layer was prepared separately on different substrates to avoid chemical and physical damage caused by process interferences. A single interconnect layer was introduced between each vertically stacked functional layer to ensure mechanical compatibility and interconnection. Compared to the previously reported layer-by-layer preparation method, the proposed method eliminates the need for tedious protection via barrier and pixel-defining layer processing steps. Additionally, based on active-matrix display, this strategy allows multiple pixels to collectively display a pattern of "1" with an aperture ratio of 83%. Moreover, the average mobility of full-photolithographic organic thin-film transistors was 1.04 cm2 V-1 s-1, ensuring stable and uniform displays. This strategy forms the basis for the construction of vertically stacked active-matrix displays, which should facilitate the commercial development of skin-like displays in wearable electronics.

A prospective phase 2 study of combination epigenetic therapy against relapsed/refractory peripheral T cell lymphoma.

BACKGROUND: Peripheral T cell lymphomas (PTCLs) are prototypical epigenetic malignancies with invariably poor prognoses. Novel and effective therapeutic strategies are needed to improve clinical outcomes, particularly in relapsed/refractory patients. METHODS: We conducted a multicenter phase 2 study to evaluate the therapeutic efficacy of azacitidine and chidamide, alone or in combination with gemcitabine and oxaliplatin (GemOx), in patients with relapsed/refractory PTCLs (registration number: ChiCTR2000037232). The primary endpoint was the best overall response rate. FINDINGS: As of May 1st, 2024, thirty patients were evaluable for efficacy and toxicity. The best overall response rate was 53.3%, meeting its primary endpoint. Among the patients with angioimmunoblastic T cell lymphoma (AITL; N = 19), a numerically higher response rate was observed, regardless of whether chemotherapy was combined, compared to patients with non-AITL. After a median follow-up of 36.6 months, median progression-free survival and overall survival were 7.1 and 8.7 months, respectively. Patients with AITL who received combination chemotherapy (N = 12) achieved the most promising response rates (overall response rate, 91.7%; complete remission rate, 66.7%) and survival outcomes (median progression-free survival, 17.2 months; median overall survival, 38.8 months). The most common grade 3-4 toxicities were neutropenia (40.0%) and thrombocytopenia (30.0%). CONCLUSIONS: The combination of epigenetic therapy with GemOx was well tolerated and highly effective in patients with relapsed/refractory PTCLs. Patients with AITL, in particular, may benefit more from this combination treatment and should be the focus of future studies. FUNDING: This work was funded by the Natural Science Foundation of Jiangsu Province (BK20232039).

Enhancing Lithium-Sulfur Battery Performance with MXene: Specialized Structures and Innovative Designs.

Established in 1962, lithium-sulfur (Li-S) batteries boast a longer history than commonly utilized lithium-ion batteries counterparts such as LiCoO2 (LCO) and LiFePO4 (LFP) series, yet they have been slow to achieve commercialization. This delay, significantly impacting loading capacity and cycle life, stems from the long-criticized low conductivity of the cathode and its byproducts, alongside challenges related to the shuttle effect, and volume expansion. Strategies to improve the electrochemical performance of Li-S batteries involve improving the conductivity of the sulfur cathode, employing an adamantane framework as the sulfur host, and incorporating catalysts to promote the transformation of lithium polysulfides (LiPSs). 2D MXene and its derived materials can achieve almost all of the above functions due to their numerous active sites, external groups, and ease of synthesis and modification. This review comprehensively summarizes the functionalization advantages of MXene-based materials in Li-S batteries, including high-speed ionic conduction, structural diversity, shuttle effect inhibition, dendrite suppression, and catalytic activity from fundamental principles to practical applications. The classification of usage methods is also discussed. Finally, leveraging the research progress of MXene, the potential and prospects for its novel application in the Li-S field are proposed.

The up-regulation of PD-L1 during boningmycin-induced senescence in human cancer cells depends on the activation of the JAK/STAT signaling pathway mediated by SASP.

Therapy-induced senescence can regulate both the innate and adaptive immune systems, thereby affecting therapeutic efficacy. Bleomycin is a major component of combined chemotherapy regimens, utilized for the treatment of multiple tumors, whereas pulmonary toxicity severely restricts its clinical benefits. As a member of the bleomycin family, boningmycin (BON) exhibits potent anticancer activity with minimal pulmonary toxicity, making it a potential alternative to bleomycin. Low concentrations of BON can induce senescence, but the impact of BON-induced senescence on anticancer immunity remains unclear. This study investigates the effects of BON-induced senescence on PD-L1 expression and the underlying mechanisms in human cancer cells. Firstly, the elevation of PD-L1 protein during BON-induced senescence was confirmed by a senescence ß-galactosidase staining assay, detection of the senescence-associated secretory phenotype (SASP), western blot and flow cytometry in human lung cancer NCI-H460 cells and breast cancer MDA-MB-231 cells. Subsequently, it was shown that the increase in PD-L1 protein is mediated by SASP, as evidenced by the use of conditional media, knockdown of cyclic GMP-AMP synthase and inhibition of stimulator of interferon genes. Ultimately, it was demonstrated that SASP-mediated PD-L1 up-regulation is dependent on the activation of the JAK/STAT pathway through the use of specific inhibitors and siRNAs. These findings clarify the impact of BON-induced senescence on PD-L1 expression and may contribute to the optimization of the therapeutic efficacy of bleomycin-related compounds and the clinical transformation of BON.

The risk and survival of multiple myeloma as the second primary malignancy in a single Chinese center.

Background: As the overall survival (OS) of patients with multiple myeloma (MM) improves, the incidence of second primary malignancy (SPM) in long-term complications increases. However, there are limited data regarding MM as a SPM. Therefore, this study aimed to determine the time trends in the incidence of MM, as well as the incidence and survival of patients with MM as the SPM. Methods: Kaplan-Meier survival analysis was performed to determine the survival curve, while a log-rank test was used to determine OS. Results: A total of 794 patients were diagnosed with MM among 7,921 patients with hematologic malignancy between 2009 and 2017. The incidence of MM showed an annual upward trend, increasing from 9.3% [2009-2011] to 10.8% [2015-2017]. Of the 794 patients with MM, 16 were diagnosed as the SPM commonly secondary to cancers of the lung (n=4), colon (n=3), breast (n=3), and other (n=6). The median survival of patients with MM as the SPM was 24.5 months (range, 1-95 months). The patients with MM without multiple malignancies had significantly longer survival (median, 46.5 months; range, 17-132 months; P=0.04). Conclusions: This retrospective study suggests that the incidence of MM may be increasing annually and that the survival of patients with MM as the second primary malignant was significantly shorter than that of those without multiple malignancies.

Fabrication of nanoparticle array membranes by integrating semi-crystalline polymer self-assembly with NIPS for water treatment.

The integration of polymer self-assembly with non-solvent induced phase separation (SNIPS) represents a recent advancement in membrane fabrication. This breakthrough allows for the fabrication of membranes with uniformly sized pores, enabling precise and fast separation through a phase inversion process commonly used in industrial fabrication. Currently, block copolymers are used in implementing the SNIPS strategy. In order to facilitate an easier and more flexible fabrication procedure, we employed the widely used semi-crystalline polymer polyvinylidene fluoride (PVDF) as the base material for achieving SNIPS through self-seeding. This process involves filtering the PVDF casting solution to induce microphase separation and generate crystal seeds. Subsequently, NIPS is applied to enable the growth of crystal seeds into uniformly distributed nanoparticles with consistent size and shape, ultimately resulting in a membrane with a uniform pore size. The fabricated membrane exhibited improved flux (2924.67 ± 28.02 L m-2 h-1 at 0.5 bar) and rejection (91% for 500 nm polystyrene particles). Notably, the microphase separation in the casting solution is a distinguishing feature of the SNIPS compared to NIPS. In this study, we found that the microphase separation of semi-crystalline polymers is also crucial for achieving membranes with uniform pore sizes. This finding may extend the potential application of the SNIPS strategy to include semi-crystalline polymers.

Self-Internal Standard Fluorescence for Ultrasensitive Detecting of mtDNA to Evaluate Matrilineal Genetic Defect Levels.

Mitochondrial DNA (mtDNA) is a unique genetic material characterized by maternal inheritance. It possesses a circular structure devoid of histone protection and exhibits low cellular abundance, which poses great challenges for its sensitive and selective detection at the living cell level. Herein, we have designed three bis-naphthylimide probes with varying linker lengths (NANn-OH, n = 0, 2, 6), facilitating the formation of distinct twisted or folded molecular conformations in the free state. These probes emit the red fluorescence around 627 nm with different fluorescence quantum yields (ΦNAN0-OH = 0.0016, ΦNAN2-OH = 0.0136, and ΦNAN6-OH = 0.0125). When encountering mtDNA (0.4-3.4 µg/mL), these probes undergo conformational changes depending on the length of the attached C-strand and exhibit a gradually increasing fluorescence signal around 453 nm. The fluorescence intensity increased to 13.5-fold, 1.9-fold, and 8.2-fold, respectively. Notably, the red fluorescence intensities around 627 nm remain constant throughout this process, thus serving as an inherent correction mechanism for proportional fluorescence signal enhancement to improve selectivity and sensitivity. NAN0-OH, NAN2-OH, and NAN6-OH showed good linearity for mtDNA in the range of 0.4-3.4 µg/mL with detection limits of LODNAN0-OH = 1.04 µg/mL, LODNAN2-OH = 1.10 µg/mL, and LODNAN6-OH = 1.15 µg/mL. Cellular experiments reveal that NAN6-OH effectively monitors curcumin-induced mtDNA damage in HepG-2 cells while enabling monitoring of genetic mtDNA damage. We anticipate that this tool holds significant potential for the precise evaluation of maternal genetic defects, thereby enhancing hypersensitive assessment in clinical medicine.

A Redox-Active Phenothiazine-based Pd2L4-Type Coordination Cage and Its Isolable Crystalline Polyradical Cations.

Polyradical cages are of great interest because they show very fascinating physical and chemical properties, but many challenges remain, especially for their synthesis and characterization. Herein, we present the synthesis of a polyradical cation cage 14⋅+ through post-synthetic oxidation of a redox-active phenothiazine-based Pd2L4-type coordination cage 1. It's worth noting that 1 exhibits excellent reversible electrochemical and chemical redox activity due to the introduction of a bulky 3,5-di-tert-butyl-4-methoxyphenyl substituent. The generation of 14⋅+ through reversible electrochemical oxidation is investigated by in situ UV/Vis-NIR and EPR spectroelectrochemistry. Meanwhile, chemical oxidation of 1 can also produce 14⋅+ which can be reversibly reduced back to the original cage 1, and the process is monitored by EPR and NMR spectroscopies. Eventually, we succeed in the isolation and single crystal X-ray diffraction analysis of 14⋅+, whose electronic structure and conformation are distinct to original 1. The magnetic susceptibility measurements indicate the predominantly antiferromagnetic interactions between the four phenothiazine radical cations in 14⋅+. We believe that our study including the facile synthesis methodology and in situ spectroelectrochemistry will shed some light on the synthesis and characterization of novel polyradical systems, opening more perspectives for developing functional supramolecular cages.

Metal stannum exposure increases the risk of congenital heart defects occurence in offspring: A case-control study in Lanzhou.

BACKGROUND: The purpose of this study was to analyse the association between stannum exposure during pregnancy and congenital heart diseases in offspring. METHODS: Based on a prospective birth cohort study conducted in Gansu Maternal and Child Health Hospital from 2010 to 2012, 14,359 pregnant women were followed up using a nested case-control study method. 97 pregnant women whose offspring were diagnosed with CHDs were used as the case group, and 194 pregnant women whose offspring did not suffer from congenital heart diseases were used as the control group in a ratio of 1:2 according to their age and place of birth. Inductively coupled plasma mass spectrometry was used to determine elemental stannum in blood samples from pregnant women hospitalized for delivery and in fetal cord blood samples. Multifactorial logistic regression analysis was used to assess the association between stannum and offspring CHDs. RESULTS: There was a moderate positive correlation between the concentration of stannum in pregnant women's blood and that in umbilical cord blood. A higher concentrations of maternal blood stannum level was associated with a greater risk of CHDs (aOR 3.409, 95%CI 1.785-6.826), isolated CHDs (aOR 4.044, 95%CI 1.803-9.070), multiple CHDs (aOR 2.625, 95%CI 1.137-6.061), patent ductus arteriosus (aOR 2.882, 95%CI 1.443-5.756), atrial septal defects (aOR 3.067, 95%CI 1.406-6.690), ventricular septal defects (aOR 7.414, 95%CI 1.414-38.874). There was a correlation between the maternal and cord blood sample suggesting stannum crosses the placenta.

Ag/MXene as Saturable Absorber for Tm:Ho Co-Doped Q-Switched Fiber Laser.

Q-switched fiber lasers have become reliable light sources for generating high-energy pulses, which can be passively modulated by saturable absorbers with excellent nonlinear optical properties. The composite combining Ag and MXene exhibits a broadband nonlinear response and high modulation depth, making it a promising candidate for saturable absorbers in pulsed lasers. Herein, we demonstrate a Q-switched Tm:Ho co-doped fiber laser centered at 2 µm, where the Ag/MXene composite serves as a saturable absorber to generate pulses. The typical spectrum, pulse train, and radio frequency spectrum of Q-switched pulses were observed, in which the 60 dB signal-to-noise ratio was higher than that of 2 µm Q-switched fiber lasers based on other materials, demonstrating the stability of the output pulses. Additionally, the long-term stability of the laser was evaluated over 2 h, where the well-maintained central wavelength and output power also indicated the robustness of the Q-switched laser. Furthermore, the influence of the pump power on the parameters of Q-switched pulses was also investigated, which is conducive to control the output characteristics of lasers. Specifically, the pulse width of the Q-switched pulse decreased, while the repetition rate, output power, and single pulse energy all increased with the increase in pump power. These experimental results demonstrate the ability of Ag/MXene as a saturable absorber and show its potential for generating high-performance pulses in ultrafast lasers.

Bioinformatics Analysis Reveals HIST1H2BH as a Novel Diagnostic Biomarker for Atrial Fibrillation-Related Cardiogenic Thromboembolic Stroke.

Atrial fibrillation (AF) is a significant precursor to cerebral embolism. Our study sought to unearth new diagnostic biomarkers for atrial fibrillation-related cerebral embolism (AF-CE) by meticulously examining multiple GEO datasets and meta-analysis. The gene expression omnibus (GEO) database provided RNA sequencing data associated with AF and stroke. We began by pinpointing genes with varied expressions in AF-CE patient blood samples. A meta-analysis was subsequently undertaken using several RNA sequencing datasets to verify these genes. LASSO regression discerned key genes for AF-CE, with their diagnostic prowess verified through ROC curve examination. Active signaling pathways within stroke patients were discerned via GO and KEGG enrichment, with PPI interactions detailing gene interplay. Differential gene analysis revealed an upregulation of sixteen genes and a downregulation of four in stroke patient blood samples. Eight genes showcased varied expression in the meta-analysis. LASSO regression zeroed in on five of these, culminating in HIST1H2BH's identification as a characteristic gene. HIST1H2BH's prowess in predicting AF-CE was confirmed through ROC. Integrin signaling, platelet activation, ECM interactions, and the PI3K-Akt pathway were found active in stroke victims. HIST1H2BH's interaction with the notably upregulated ITGA2B was spotlighted by PPI. Additionally, HIST1H2BH exhibited links with NK cells and eosinophils. HIST1H2BH emerges as an insightful diagnostic beacon for AF-CE. Its presence, post AF, potentially modulates pathways, accentuating platelet activation and consequent thrombus generation, leading to cerebral embolism.

Chiral Brønsted Base Activation of Donor-Acceptor Cyclopropanes toward Diastereo- and Enantioselective [3 + 2] Cycloaddition with Isatin-Derived Ketimines.

Organocatalyzed diastereo- and enantioselective [3 + 2] cycloaddition reactions of donor-acceptor (D-A) cyclopropanes with isatin-derived ketimines are presented. Different from well-developed Lewis acid activation protocols which promote the reactivity of D-A cyclopropanes through coordinating to the acceptor group, in this reaction, dicyanocyclopropylmethyl ketones can be activated through nucleophilic activation of the donor group by using dihydroquinine-derived squaramide as Brønsted base catalyst. The reaction affords functionalized spiro[oxindole-3,2'-pyrrolidines] with two nonadjacent tetra- and tri-substituted stereocenters in 83-99% yields, moderate to excellent diastereoselectivities (up to >20:1 diastereomeric ratio (dr)), and excellent enantioselectivities (up to >99% enantiomeric excess (ee)) under mild conditions.

3D Bioprinting of Artificial Skin Substitute with Improved Mechanical Property and Regulated Cell Behavior through Integrating Patterned Nanofibrous Films.

Three-dimensional (3D) bioprinting has advantages for constructing artificial skin tissues in replicating the structures and functions of native skin. Although many studies have presented improved effect of printing skin substitutes in wound healing, using hydrogel inks to fabricate 3D bioprinting architectures with complicated structures, mimicking mechanical properties, and appropriate cellular environments is still challenging. Inspired by collagen nanofibers withstanding stress and regulating cell behavior, a patterned nanofibrous film was introduced to the printed hydrogel scaffold to fabricate a composite artificial skin substitute (CASS). The artificial dermis was printed using gelatin-hyaluronan hybrid hydrogels containing human dermal fibroblasts with gradient porosity and integrated with patterned nanofibrous films simultaneously, while the artificial epidermis was formed by seeding human keratinocytes upon the dermis. The collagen-mimicking nanofibrous film effectively improved the tensile strength and fracture resistance of the CASS, making it sewable for firm implantation into skin defects. Meanwhile, the patterned nanofibrous film also provided the biological cues to guide cell behavior. Consequently, CASS could effectively accelerate the regeneration of large-area skin defects in mouse and pig models by promoting re-epithelialization and collagen deposition. This research developed an effective strategy to prepare composite bioprinting architectures for enhancing mechanical property and regulating cell behavior, and CASS could be a promising skin substitute for treating large-area skin defects.

The correlation between menstrual characteristics and fertility in women of reproductive age: a systematic review and meta-analysis.

IMPORTANCE: Menstruation serves as an indicator of women's reproductive well-being and plays a pivotal role in their fertility; nevertheless, there remains an ongoing debate regarding the epidemiological evidence linking menstrual characteristics as well as fertility. OBJECTIVE: To explore the correlation between menstrual characteristics and fertility in women of reproductive age. DATA SOURCES: A comprehensive literature search was conducted using PubMed, Embase, Web of Science, and Cochrane libraries to identify research articles published up until February 9, 2024. STUDY SELECTION AND SYNTHESIS: We included all studies in which the relationship between menstrual characteristics and pregnancy rates among women of reproductive age was investigated. We excluded studies involving the administration of oral contraceptives, the application of assisted reproductive technologies, and individuals with a documented history of infertility or partners with a known history of infertility. MAIN OUTCOME MEASURE(S): Clinical pregnancy and miscarriage. RESULT(S): This meta-analysis was composed of nine studies involving a total of 399,966 women, and the evidential quality derived from these studies was deemed to be high with a low risk of bias. Compared with a normal menstrual cycle length (25-32 days), the impact of a short (<25 days) or long (>32 days) menstrual cycle on a woman's pregnancy was relatively insignificant ([odds ratio {OR}, 0.81; 95% confidence interval {CI}, 0.65-1.01; I2, 68%]; [OR, 0.89; 95% CI, 0.75-1.06; I2, 60%], respectively); however, a change in cycle length may increase the risk of miscarriage ([relative risk, 1.87; 95% CI, 1.11-3.15; I2, 0]; [relative risk, 1.66; 95% CI, 1.07, 2.57; I2, 43%], respectively). In comparison to women experiencing menarche at a typical age (12-14 years), those with a late age at menarche (>14 years) exhibited a decreased likelihood of pregnancy (OR, 0.92; 95% CI, 0.91-0.93; I2, 0%); and compared with women experiencing a normal duration of menstrual bleeding (4-7 days), those with a short duration of menstrual bleeding (<4 days) exhibited reduced fertility potential (OR, 0.86; 95% CI, 0.84-0.88; I2, 29%). CONCLUSION(S): Short and long menstrual cycle lengths may elevate women's susceptibility to spontaneous abortion, whereas late age at menarche as well as short duration of menstrual bleeding appear to be linked to diminished fertility among women of reproductive age. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42023487458 (9 December 2023).