Efficacy and safety of sovleplenib (HMPL-523) in adult patients with chronic primary immune thrombocytopenia in China (ESLIM-01): a randomised, double-blind, placebo-controlled, phase 3 study.

BACKGROUND: Sovleplenib, a novel spleen tyrosine kinase (SYK) inhibitor, showed promising safety and activity in patients with primary immune thrombocytopenia in a phase 1b/2 trial. We aimed to evaluate the efficacy and safety of sovleplenib in patients with chronic primary immune thrombocytopenia. METHODS: This randomised, double-blind, placebo-controlled, phase 3 trial (ESLIM-01) was done in 34 clinical centres in China. Eligible patients, aged 18-75 years, had chronic primary immune thrombocytopenia, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and received one or more previous treatments. Patients were randomly assigned (2:1) to receive oral sovleplenib or placebo, 300 mg once daily, for 24 weeks. Randomisation was stratified by baseline platelet counts, previous splenectomy, and concomitant treatment for anti-immune thrombocytopenia at baseline. The primary endpoint was durable response rate (proportion of patients with a platelet count of ≥50 × 109/L on at least four of six scheduled visits between weeks 14 and 24, not affected by rescue treatment) assessed by intention-to-treat. The trial is registered with ClinicalTrials.gov, NCT05029635, and the extension, open-label phase is ongoing. FINDINGS: Between Sept 29, 2021, and Dec 31, 2022, 188 patients were randomly assigned to receive sovleplenib (n=126) or placebo (n=62). 124 (66%) were female, 64 (34%) were male, and all were of Asian ethnicity. Median previous lines of immune thrombocytopenia therapy were 4·0, and 134 (71%) of 188 patients had received previous thrombopoietin or thrombopoietin receptor agonist. The primary endpoint was met; durable response rate was 48% (61/126) with sovleplenib compared with zero with placebo (difference 48% [95% CI 40-57]; p<0·0001). The median time to response was 8 days with sovleplenib compared with 30 days with placebo. 125 (99%) of 126 patients in the sovleplenib group and 53 (85%) of 62 in the placebo group reported treatment-emergent adverse events (TEAEs), and most events were mild or moderate. Frequent TEAEs of grade 3 or higher for sovleplenib versus placebo were platelet count decreased (7% [9/126] vs 10% [6/62]), neutrophil count decreased (3% [4/126] vs 0% [0/62]), and hypertension (3% [4/126] vs 0% [0/62]). Incidences of serious TEAEs were 21% (26/126) in the sovleplenib group and 18% (11/62) in the placebo group. There were no deaths in the study. INTERPRETATION: Sovleplenib showed a clinically meaningful sustained platelet response in patients with chronic primary immune thrombocytopenia, with a tolerable safety profile and improvement in quality of life. Sovleplenib could be a potential treatment option for patients with immune thrombocytopenia who received one or more previous therapy. FUNDING: HUTCHMED and Science and Technology Commission of Shanghai Municipality.

Multi-Group Polymer Coating on Zn Anode for High Overall Conversion Efficiency Photorechargeable Zinc-Ion Batteries.

The solar-driven photorechargeable zinc-ion batteries have emerged as a promising power solution for smart electronic devices and equipment. However, the subpar cyclic stability of the Zn anode remains a significant impediment to their practical application. Herein, poly(diethynylbenzene-1,3,5-triimine-2,4,6-trione) (PDPTT) was designed as a functional polymer coating of Zn. Theoretical calculations demonstrate that the PDPTT coating not only significantly homogenizes the electric field distribution on the Zn surface, but also promotes ion-accessible surface of Zn. With multiple N and C=O groups exhibiting strong adsorption energies, this polymer coating reduces the nucleation overpotential of Zn, alters the diffusion pathway of Zn2+ at the anode interface, and decreases the corrosion current and hydrogen evolution current. Leveraging these advantages, Zn-PDPTT//Zn-PDPTT exhibits an exceptionally long cycling time (≥4300 h, 1 mA cm-2). Zn-PDPTT//AC zinc-ion hybrid capacitors can withstand 50,000 cycles at 5 A/g. Zn-PDPTT//NVO zinc-ion battery exhibits a faster charge storage rate, higher capacity, and excellent cycling stability. Coupling Zn-PDPTT//NVO with high-performance perovskite solar cells results in a 13.12% overall conversion efficiency for the photorechargeable zinc-ion battery, showcasing significant value in advancing the efficiency and upgrading conversion of renewable energy utilization.

Construction of a pillar[5]arene-based supramolecular chiral polymer linked to aminophosphine salt for chiral recognition of enantiomers of mandelic acid.

In recent years, supramolecular chirality has been greatly developed in asymmetric synthesis, chiral sensing and other research fields, but its application in molecular chiral recognition has not been extensively studied. In this paper, L-Boc-tyrosine methoxyester and phosphorus chloride salts were introduced into the framework of pillar[n]arene, and a pillar[5]arene-based supramolecular chiral polymer L-TPP-P was constructed. The supramolecular polymer had stable supramolecular chiral properties and could be used as a chiral solvation reagent for chiral recognition of mandelic acid MA. The molar ratio method and Scatchard plot showed that the complexation ratio of L-TPP-P (pillar[5]arene monomer as the reference object) and MA was 1 : 1, and the complexation constants of L-TPP-P with R-MA and S-MA were 4.51 × 105 M-1 and 6.5 × 104 M-1, respectively. The significant affinity difference of L-TPP-P for different enantiomers of MA showed the excellent chiral recognition and stereoselectivity of pillar[5]arene-based supramolecular polymers for MA. This study provides a new idea for a novel supramolecular polymer chiral recognition reagent or chiral recognition method.

Old people's preference for nursing homes in East China: a discrete choice experiment.

BACKGROUND: The aged people who live in nursing home are predicted to keep growing in the following decades. There are both quantitative imbalance and structural imbalance in the utilization of nursing homes in China. This study aimed to analyze old people's preference for nursing homes and help the government optimize resource allocation. METHODS: A discrete choice experiment (DCE) was conducted and six attributes of nursing homes including monthly fee, distance from home, geographical location, medical facilities, environment of nursing homes and nursing staff were determined. Respondents were recruited from Nantong and Yangzhou city, China. In each city, two communities or villages were randomly selected. In each community/village, about 65 old people were randomly selected. Analysis was conducted using mixed logit regression models to determine preferences for potential attributes. RESULTS: A total of 233 old people were included in the analysis. The findings indicated that all six attributes were statistically significant factors for participants. "Professional nursing staff" was the most important characteristic to participants, followed by "Medical facilities". Compared with female, the males preferred professional nursing staff (ß = 2.939 vs. ß = 2.643, P < 0.001), medical facilities (ß = 1.890 vs. ß = 1.498, P < 0.001), and the environment (ß = 0.752, P < 0.01). For different age groups, participants aged 60-69 didn't pay attention to distance and location, while those aged 80 and above only paid attention to professional nursing staff and medical facilities. CONCLUSIONS: The present study provides important insights into the characteristics of nursing home that are most preferred by old people. Authorities should take into account old people's preference in the planning, design and evaluation of nursing homes.

Non-invasive prediction model of histologic chorioamnionitis with preterm prelabour rupture of membranes.

BACKGROUND: The aim of this study is to identify risk factors associated with histological chorioamnionitis (HCA) and develop a predictive model for antepartum assessment of the risk of PPROM with HCA. METHODS: This study retrospectively analyzed pregnant women who experienced PPROM between 25 + 0 and 35 + 0 weeks of gestational age. The women were divided into two groups based on the presence or absence of HCA. Univariate and multivariate logistic regression analyses were conducted to identify maternal risk factors and develop a clinical prediction model for HCA. The model's discrimination and consistency were evaluated using receiver operating characteristic (ROC) and calibration curves. RESULTS: Seventeen thousand one hundred forty-six (17,146) pregnant women were screened, and 726 (4.23 %) had PPROM. Out of the 286 subjects with PPROM, 160 developed HCA. The maternal age of these subjects ranged from 18 to 43 years (30.0 ± 5.4), while their gestational age (GA) ranged from 25 + 0 to 35 + 0 weeks (31.6 ± 2.0). The average GA at delivery was 32.2 ± 2.0 (weeks).Compared with the non-HCA group, the expectant time > 48 h, GA at delivery > 32 weeks, twin pregnancy, HGB (<110 g/Lg/L), degree of LGB (IIb-III), and WBC (>9.5 × 109 /L) were significantly more than in the PPROM with HCA group. The results show that the best model was obtained by leave-one-out logistic regression (AUC = 0.785, CA = 0.741, F1 = 0.739, Precision = 0.740, Recall = 0.741). In the validation set, logistic regression also achieved good results (AUC = 0.710, CA = 0.671, F1 = 0.654, Precision = 0.683, Recall = 0.671). Combining the previous analysis, we found that the prognostic model constructed using the core six features had the best predictive effect. CONCLUSIONS: Six features were associated with the occurrence of chorioamnionitis. These features were used to construct a diagnostic model that can accurately predict the probability of chorioamnionitis occurrence and provide a beneficial tool for the prevention and management of PPROM with HCA.

The intricate dance of tumor evolution: Exploring immune escape, tumor migration, drug resistance, and treatment strategies.

Recent research has unveiled fascinating insights into the intricate mechanisms governing tumor evolution. These studies have illuminated how tumors adapt and proliferate by exploiting various factors, including immune evasion, resistance to therapeutic drugs, genetic mutations, and their ability to adapt to different environments. Furthermore, investigations into tumor heterogeneity and chromosomal aberrations have revealed the profound complexity that underlies the evolution of cancer. Emerging findings have also underscored the role of viral influences in the development and progression of cancer, introducing an additional layer of complexity to the field of oncology. Tumor evolution is a dynamic and complex process influenced by various factors, including immune evasion, drug resistance, tumor heterogeneity, and viral influences. Understanding these elements is indispensable for developing more effective treatments and advancing cancer therapies. A holistic approach to studying and addressing tumor evolution is crucial in the ongoing battle against cancer. The main goal of this comprehensive review is to explore the intricate relationship between tumor evolution and critical aspects of cancer biology. By delving into this complex interplay, we aim to provide a profound understanding of how tumors evolve, adapt, and respond to treatment strategies. This review underscores the pivotal importance of comprehending tumor evolution in shaping effective approaches to cancer treatment.

The Antioxidant Mechanism of Peptides Extracted from Tuna Protein Revealed Using a Molecular Docking Simulation.

Tuna protein serves as a significant source of bioactive peptides, and its functional properties can be elucidated through predictive modeling, followed by experimental validation. In this study, the active polypeptides were obtained from tuna protein via enzymatic hydrolysis (TPP), and their peptide sequences were determined. Furthermore, the potential activity of these peptides was predicted, focusing on antioxidant peptides, and compared to the sequence library of known antioxidant peptides to identify common structural motifs. The accuracy of the prediction results was confirmed through in vitro antioxidant assays and molecular docking studies. We identified seven specific peptide segments derived from tuna protein that exhibit antioxidant potential, accounting for approximately 15% of all active peptides. Molecular docking and cell experiments were employed to provide compelling evidence for the presence of antioxidant peptides within tuna protein. This study not only lays a solid foundation for studying the structure of active peptides but also opens up a novel avenue for an expedited assessment of their properties.

A ferroelectric fin diode for robust non-volatile memory.

Among today's nonvolatile memories, ferroelectric-based capacitors, tunnel junctions and field-effect transistors (FET) are already industrially integrated and/or intensively investigated to improve their performances. Concurrently, because of the tremendous development of artificial intelligence and big-data issues, there is an urgent need to realize high-density crossbar arrays, a prerequisite for the future of memories and emerging computing algorithms. Here, a two-terminal ferroelectric fin diode (FFD) in which a ferroelectric capacitor and a fin-like semiconductor channel are combined to share both top and bottom electrodes is designed. Such a device not only shows both digital and analog memory functionalities but is also robust and universal as it works using two very different ferroelectric materials. When compared to all current nonvolatile memories, it cumulatively demonstrates an endurance up to 1010 cycles, an ON/OFF ratio of ~102, a feature size of 30 nm, an operating energy of ~20 fJ and an operation speed of 100 ns. Beyond these superior performances, the simple two-terminal structure and their self-rectifying ratio of ~ 104 permit to consider them as new electronic building blocks for designing passive crossbar arrays which are crucial for the future in-memory computing.

Macro CD5L+ deteriorates CD8+T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma.

Intratumoral immune status influences tumor therapeutic response, but it remains largely unclear how the status determines therapies for patients with intrahepatic cholangiocarcinoma. Here, we examine the single-cell transcriptional and TCR profiles of 18 tumor tissues pre- and post- therapy of gemcitabine plus oxaliplatin, in combination with lenvatinib and anti-PD1 antibody for intrahepatic cholangiocarcinoma. We find that high CD8 GZMB+ and CD8 proliferating proportions and a low Macro CD5L+ proportion predict good response to the therapy. In patients with a poor response, the CD8 GZMB+ and CD8 proliferating proportions are increased, but the CD8 GZMK+ proportion is decreased after the therapy. Transition of CD8 proliferating and CD8 GZMB+ to CD8 GZMK+ facilitates good response to the therapy, while Macro CD5L+-CD8 GZMB+ crosstalk impairs the response by increasing CTLA4 in CD8 GZMB+. Anti-CTLA4 antibody reverses resistance of the therapy in intrahepatic cholangiocarcinoma. Our data provide a resource for predicting response of the combination therapy and highlight the importance of CD8+T-cell status conversion and exhaustion induced by Macro CD5L+ in influencing the response, suggesting future avenues for cancer treatment optimization.

Relationship between vaginal microbiota and chorioamnionitis: A prospective cohort study.

OBJECTIVE: This study aimed to determine the association between vaginal microbiota and chorioamnionitis and its predictive value. METHODS: Thirty pregnant women in their third trimester were prospectively recruited. The participants were categorized into three groups based on their clinical manifestations and placental pathology: the clinical chorioamnionitis group (IP group), the asymptomatic histological chorioamnionitis group (CP group), and the healthy control group (CN group). Basic data and medical history were collected from each participant. Vaginal samples were collected before delivery and analyzed using microbial diversity sequencing. RESULTS: No significant differences were observed in age, body mass index, and education among the groups (P > 0.05). However, the IP group exhibited higher rates of low birth weight (60 % vs 20 % vs 0 %, P = 0.008) and respiratory distress syndrome (50 % vs 20 % vs 0 %, P = 0.003) compared with the CP and CN groups. The Shannon index [2.09 (1.16-3.86) vs 0.84 (0.19-1.11) vs 0.44 (0.25-0.85), P = 0.009] and Simpson index [0.70 (0.41-0.81) vs 0.26 (0.04-0.39) vs 0.11 (0.05-0.29), P = 0.010] in the IP group were higher than those in the CN and CP groups. ß diversity analysis indicated that the microbial community structure differed among the three groups, with a 14.1 % variation associated with group differences (P = 0.002). At the genus level, the random forest model revealed that Lactobacillus, Dialister, Prevotella, Ligilactobacillus, and Anaerococcus had Gini indexes higher than 1. Further, linear discriminant analysis (LDA) demonstrated that the abundance of Lactobacillus crispatus in the IP group was lower than in the CN group (LDA >4.0, mean relative abundance 9.19 % vs 54.40 %, P = 0.031). The logistic regression analysis indicated that a decreased abundance of L. crispatus was associated with an increased risk of clinical chorioamnionitis. CONCLUSIONS: The reduction of L. crispatus and increasing trend of specific anaerobic groups are associated with the onset of chorioamnionitis, suggesting their potential value in chorioamnionitis identification. The vaginal microbiota could serve as a useful biomarker for predicting future disease and tailoring surveillance efforts. Additionally, it may present a viable target for developing prevention and therapeutic strategies.

Ultrahigh-gain organic transistors based on van der Waals metal-barrier interlayer-semiconductor junction.

Intrinsic gain is a vital figure of merit in transistors, closely related to signal amplification, operation voltage, power consumption, and circuit simplification. However, organic thin-film transistors (OTFTs) targeted at high gain have suffered from challenges such as narrow subthreshold operating voltage, low-quality interface, and uncontrollable barrier. Here, we report a van der Waals metal-barrier interlayer-semiconductor junction-based OTFT, which shows ultrahigh performance including ultrahigh gain of ~104, low saturation voltage, negligible hysteresis, and good stability. The high-quality van der Waals-contacted junctions are mainly attributed to patterning EGaIn liquid metal electrodes by low-energy microfluidic processes. The wide-bandgap semiconductor Ga2O3 as barrier interlayer is achieved by in situ surface oxidation of EGaIn electrodes, allowing for an adjustable barrier height and expected thermionic emission properties. The organic inverters with a high gain of 5130 and a simplified current stabilizer are further demonstrated, paving a way for high-gain and low-power organic electronics.

Epidural combined optical and electrical stimulation induces high-specificity activation of target muscles in spinal cord injured rats.

Introduction: Epidural electrical stimulation (EES) has been shown to improve motor dysfunction after spinal cord injury (SCI) by activating residual locomotor neural networks. However, the stimulation current often spreads excessively, leading to activation of non-target muscles and reducing the accuracy of stimulation regulation. Objectives: Near-infrared nerve stimulation (nINS) was combined with EES to explore its regulatory effect on lower limb muscle activity in spinal-cord-transected rats. Methods: In this study, stimulation electrodes were implanted into the rats' L3-L6 spinal cord segment with T8 cord transected. Firstly, a series of EES parameters (0.2-0.6 mA and 20-60 Hz) were tested to determine those that specifically regulate the tibialis anterior (TA) and medial gastrocnemius (MG). Subsequently, to determine the effect of combined optical and electrical stimulation, near-infrared laser with a wavelength of 808 nm was used to irradiate the L3-L6 spinal cord segment while EES was performed. The amplitude of electromyography (EMG), the specific activation intensity of the target muscle, and the minimum stimulus current intensity to induce joint movement (motor threshold) under a series of optical stimulation parameters (power: 0.0-2.0 W; pulse width: 0-10 ms) were investigated and analyzed. Results: EES stimulation with 40 Hz at the L3 and L6 spinal cord segments specifically activated TA and MG, respectively. High stimulation intensity (>2 × motor threshold) activated non-target muscles, while low stimulation frequency (<20 Hz) produced intermittent contraction. Compared to electrical stimulation alone (0.577 ± 0.081 mV), the combined stimulation strategy could induce stronger EMG amplitude of MG (1.426 ± 0.365 mV) after spinal cord injury (p < 0.01). The combined application of nINS effectively decreased the EES-induced motor threshold of MG (from 0.237 ± 0.001 mA to 0.166 ± 0.028 mA, p < 0.001). Additionally, the pulse width (PW) of nINS had a slight impact on the regulation of muscle activity. The EMG amplitude of MG only increased by ~70% (from 3.978 ± 0.240 mV to 6.753 ± 0.263 mV) when the PW increased by 10-fold (from 1 to 10 ms). Conclusion: The study demonstrates the feasibility of epidural combined electrical and optical stimulation for highly specific regulation of muscle activity after SCI, and provides a new strategy for improving motor dysfunction caused by SCI.

Wafer-scale organic-on-III-V monolithic heterogeneous integration for active-matrix micro-LED displays.

The organic thin-film transistor is advantageous for monolithic three-dimensional integration attributed to low temperature and facile solution processing. However, the electrical properties of solution deposited organic semiconductor channels are very sensitive to the substrate surface and processing conditions. An organic-last integration technology is developed for wafer-scale heterogeneous integration of a multi-layer organic material stack from solution onto the non-even substrate surface of a III-V micro light emitting diode plane. A via process is proposed to make the via interconnection after fabrication of the organic thin-film transistor. Low-defect uniform organic semiconductor and dielectric layers can then be formed on top to achieve high-quality interfaces. The resulting organic thin-film transistors exhibit superior performance for driving micro light emitting diode displays, in terms of milliampere driving current, and large ON/OFF current ratio approaching 1010 with excellent uniformity and reliability. Active-matrix micro light emitting diode displays are demonstrated with highest brightness of 150,000 nits and highest resolution of 254 pixels-per-inch.

An Exosome-Related Long Non-coding RNA (lncRNA)-Based Signature for Prognosis and Therapeutic Interventions in Lung Adenocarcinoma.

Background The poor prognosis of lung adenocarcinoma (LUAD) has been confirmed by a large number of studies, so it is necessary to construct a prognosis model. In addition, exosome is closely related to tumors, but there are few studies on exosome-related long non-coding RNA (lncRNA) (ExolncRNA). Methods In this study, we designed a prognostic model, exosome-related lncRNA-based signature (ExoLncSig), using ExolncRNA expression profiles of LUAD patients from The Cancer Genome Atlas (TCGA). ExolncRNAs were identified through univariate and multivariate and Lasso analyses. Subsequently, based on the ExoLncSig, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, immune function and immunotherapy analysis, drug screening, and so on were performed. Results AC026355.2, AC108136.1, AL590428.1, and LINC01312 were examined to establish the ExoLncSig. Gene enrichment analysis identified potential prognostic markers and therapeutic targets, including human leukocyte antigen (HLA), parainflammation, chemokine receptor (CCR), antigen-presenting cell (APC) co-inhibition, cancer-associated fibroblast (CAF), and myeloid-derived suppressor cell (MDSC). Moreover, we ascertained that the high-risk subgroup exhibits heightened susceptibility to pharmaceutical agents. Conclusion Our findings indicate that ExoLncSig holds promise as a valuable prognostic marker in LUAD. Furthermore, the immunogenic properties of ExolncRNAs may pave the way for the development of a therapeutic vaccine against LUAD.

Copper-mediated novel cell death pathway in tumor cells and implications for innovative cancer therapies.

Previous investigations have unraveled an array of cellular demise modalities, encompassing apoptosis, necrosis, pyroptosis, iron death, and several others. These diverse pathways of cell death have been harnessed as therapeutic strategies for eradicating tumor cells. Recent scientific inquiries have unveiled a novel mode of cell death, namely copper death, which is contingent upon intracellular copper levels. Diverging from conventional cell death mechanisms, copper death exhibits a heightened reliance on mitochondrial respiration, specifically the tricarboxylic acid (TCA) cycle. Tumor cells exhibit distinctive metabolic profiles and an elevated copper content compared to their normal counterparts. The emergence of copper death presents a tantalizing prospect for targeted therapies in the realm of cancer treatment. Thus, the primary objective of this review is to introduce the proteins and intricate mechanisms underlying copper death, while comprehensively summarizing the extensive body of knowledge concerning its ramifications across diverse tumor types. The insights garnered from this comprehensive synthesis will serve as an invaluable reference for driving the development of tailor-made therapeutic interventions for tumors.

Predicting of elderly population structure and density by a novel grey fractional-order model with theta residual optimization: a case study of Shanghai City, China.

BACKGROUND: Accurately predicting the future development trend of population aging is conducive to accelerating the development of the elderly care industry. This study constructed a combined optimization grey prediction model to predict the structure and density of elderly population. METHODS: In this paper, a GT-FGM model is proposed, which combines Theta residual optimization with fractional-order accumulation operator. Fractional-order accumulation can effectively weaken the randomness of the original data sequence. Meanwhile, Theta residual optimization can adjust parameter by minimizing the mean absolute error. And the population statistics of Shanghai city from 2006 to 2020 were selected for prediction analysis. By comparing with the other traditional grey prediction methods, three representative error indexes (MAE, MAPE, RMSE) were conducting for error analysis. RESULTS: Compared with the FGM model, GM (1,1) model, Verhulst model, Logistic model, SES and other classical prediction methods, the GT-FGM model shows significant forecasting advantages, and its multi-step rolling prediction accuracy is superior to other prediction methods. The results show that the elderly population density in nine districts in Shanghai will exceed 0.5 by 2030, among which Huangpu District has the highest elderly population density, reaching 0.6825. There has been a steady increase in the elderly population over the age of 60. CONCLUSIONS: The GT-FGM model can improve the prediction accuracy effectively. The elderly population in Shanghai shows a steady growth trend on the whole, and the differences between districts are obvious. The government should build a modern pension industry system according to the aging degree of the population in each region, and promote the balanced development of each region.

Relationship between placental pathology and neonatal outcomes.

Objective: To evaluate the relationship between maternal vascular malperfusion and acute intrauterine infection/inflammation with neonatal outcomes. Methods: This was a retrospective study of women with singleton pregnancies who completed placenta pathological examination. The aim was to study the distribution of acute intrauterine infection/inflammation and maternal placental vascular malperfusion among groups with preterm birth and/or rupture of membranes. The relationship between two subtypes of placental pathology and neonatal gestational age, birth weight Z-score, neonatal respiratory distress syndrome, and intraventricular hemorrhage was further explored. Results: 990 pregnant women were divided into four groups, including 651 term, 339 preterm, 113 women with premature rupture of membranes, and 79 with preterm premature rupture of membranes. The incidence of respiratory distress syndrome and intraventricular hemorrhage in four groups were (0.7%, 0.0%, 31.9%, 31.6%, P < 0.001) and (0.9%, 0.9%, 20.0%, 17.7%, P < 0.001), respectively. The incidence of maternal vascular malperfusion and acute intrauterine infection/inflammation were (82.0%, 77.0%, 75.8%, 72.1%, P = 0.06) and (21.9%, 26.5%, 23.1%, 44.3%, P = 0.010), respectively. Acute intrauterine infection/inflammation was associated with shorter gestational age (adjusted difference -4.7 weeks, P < 0.001) and decreased weight (adjusted Z score -2.6, P < 0.001) than those with no lesions in preterm birth. When two subtype placenta lesions co-occurrence, shorter gestational age (adjusted difference -3.0 weeks, P < 0.001) and decreased weight (adjusted Z score -1.8, P < 0.001) were observed in preterm. Consistent findings were observed in preterm births with or without premature rupture of membranes. In addition, acute infection/inflammation and maternal placenta malperfusion alone or in combination were associated with an increased risk of neonatal respiratory distress syndrome (adjusted odds ratio (aOR) 0.8, 1.5, 1.8), but the difference was not statistically significant. Conclusion: Maternal vascular malperfusion and acute intrauterine infection/inflammation alone or co-occurrence are associated with adverse neonatal outcomes, which may provide new ideas for clinical diagnosis and treatment.

A Visual Color Response Test Paper for the Detection of Hydrogen Sulfide Gas in the Air.

Hydrogen sulfide (H2S) is widely found in oil and natural gas wells and industrial wastewater tanks. Owing to its high toxicity, the monitoring and detection of H2S in the air is essential. However, recent techniques for the quantitative detection of H2S gas suffer from limitations such as high cost, complicated operation, and insufficient sensitivity, preventing their practical application in industry. Thus, we have developed a portable test paper for real-time and inexpensive monitoring of H2S gas by color changes. The test paper had a significantly low H2S detection limit of 200 ppb, which is considered safe for humans. Moreover, the color of the test paper did not change noticeably when exposed to CO2, N2, O2, and air environments, indicating that the test paper is selective for H2S gas and can be stored for a long time. In addition, we fitted a color difference linear model between the color difference values (ΔE) and the concentrations of H2S gas. The establishment of the linear model substantiates that the test paper can provide accurate intensity information when detecting H2S gas leakage.

Different macaque brain network remodeling after spinal cord injury and NT3 treatment.

Graph theory-based analysis describes the brain as a complex network. Only a few studies have examined modular composition and functional connectivity (FC) between modules in patients with spinal cord injury (SCI). Little is known about the longitudinal changes in hubs and topological properties at the modular level after SCI and treatment. We analyzed differences in FC and nodal metrics reflecting modular interaction to investigate brain reorganization after SCI-induced compensation and neurotrophin-3 (NT3)-chitosan-induced regeneration. Mean inter-modular FC and participation coefficient of areas related to motor coordination were significantly higher in the treatment animals than in the SCI-only ones at the late stage. The magnocellular part of the red nucleus may reflect the best difference in brain reorganization after SCI and therapy. Treatment can enhance information flows between regions and promote the integration of motor functions to return to normal. These findings may reveal the information processing of disrupted network modules.

Integrated Microbiota and Metabolome Analysis to Assess the Effects of the Solid-State Fermentation of Corn-Soybean Meal Feed Using Compound Strains.

Solid-state fermentation is known to improve plant-based feed nutritional quality; however, the association between microbes and metabolite production in fermented feed remains unclear. We inoculated corn-soybean-wheat bran (CSW) meal feed with Bacillus licheniformis Y5-39, Bacillus subtilis B-1, and lactic acid bacteria RSG-1. Then, 16S rDNA sequencing and untargeted metabolomic profiling were applied to investigate changes in the microflora and metabolites, respectively, and their integrated correlations during fermentation were assessed. The results indicated that trichloroacetic acid soluble protein levels showed a sharp increase, while glycinin and ß-conglycinin levels showed a sharp decrease in the fermented feed, as confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Pediococcus, Enterococcus, and Lactobacillus were predominant in the fermented feed. Overall, 699 significantly different metabolites were identified before and after fermentation. Arginine and proline, cysteine and methionine, and phenylalanine and tryptophan metabolism were the key pathways, with arginine and proline metabolism being the most important pathway in the fermentation process. By analyzing the correlation between the microbiota and metabolite production, lysyl-valine and lysyl-proline levels were found to be positively correlated with Enterococcus and Lactobacillus abundance. However, Pediococcus was positively correlated with some metabolites contributing to nutritional status and immune function. According to our data, Pediococcus, Enterococcus, and Lactobacillus mainly participate in protein degradation, amino acid metabolism, and lactic acid production in fermented feed. Our results provide new insights into the dynamic changes in metabolism that occurred during the solid-state fermentation of corn-soybean meal feed using compound strains and should facilitate the optimization of fermentation production efficiency and feed quality.