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Traditional hepatocellular carcinoma-chip models lack the cell structure and microenvironments necessary for high pathophysiological correlation, leading to low accuracy in predicting drug efficacy and high production costs. This study proposed a decellularized hepatocellular carcinoma-on-a-chip model to screen anti-tumor nanomedicine. In this model, human hepatocellular carcinoma (HepG2) and human normal liver cells (L02) were co-cultured on a three-dimensional (3D) decellularized extracellular matrix (dECM) in vitro to mimic the tumor microenvironments of human hepatocellular carcinoma in vivo. Additionally, a smart nanomedicine was developed by encapsulating doxorubicin (DOX) into the ferric oxide (Fe 3 O 4 )-incorporated liposome nanovesicle (NLV/Fe+DOX). NLV/Fe+DOX selectively killed 78.59% ± 6.78% of HepG2 cells through targeted delivery and synergistic chemo-chemodynamic-photothermal therapies, while the viability of surrounding L02 cells on the chip model retained high, at over 90.0%. The drug efficacy tested using this unique chip model correlated well with the results of cellular and animal experiments. In summary, our proposed hepatocellular carcinoma-chip model is a low-cost yet accurate drug-testing platform with significant potential for drug screening., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We evaluated the diagnostic accuracy of various international guideline criteria for identifying HBeAg-positive chronic HBV infection patients with no significant liver disease. A total of 1108 HBeAg-positive CHB patients were retrospectively enrolled. The guidelines assessed included those from the European Association for the Study of the Liver (EASL) 2017, the American Association for the Study of the Liver Disease (AASLD) 2018, the Asian Pacific Association for the Study of the Liver (APASL) 2015 and the Chinese Society of Hepatology (CSH) 2022. The CSH criteria demonstrated a higher proportion of patients with G0-1 and S0-1 (82.9%) compared to the EASL (75.9%), AASLD (75.3%) and APASL groups (58.8%). Additionally, the CSH criteria exhibited a significantly higher predictive value (AUC 0.782, 95% CI 0.754-0.809) than the EASL (AUC 0.765, 95% CI 0.737-0.793), AASLD (AUC 0.749, 95% CI 0.720-0.778) and APASL (AUC 0.720, 95% CI 0.690-0.750) criteria for identifying G0-1 and S0-1. Adding quantitative HBsAg levels (> 10 4  IU/mL) to the EASL, AASLD and APASL criteria improved diagnostic performance. Consequently, the CSH guideline thresholds showed higher accuracy in identifying Chinese HBeAg-positive patients with no significant liver disease compared to EASL, AASLD and APASL criteria, emphasising the importance of considering quantitative HBsAg in the evaluation of HBeAg-positive chronic HBV infection., (© 2024 John Wiley & Sons Ltd.)

Importance: Cardiovascular-kidney-metabolic (CKM) syndrome-a novel, multistage, multisystem disorder as defined by the American Heart Association-is highly prevalent in the US. However, the prevalence of CKM stages by social determinants of health (SDOH) remains unclear., Objective: To investigate whether the prevalence of CKM stages varies by SDOH in US adults., Design, Setting, and Participants: This cross-sectional study used data from the National Health and Nutrition Examination Survey (1999-2018) and included a nationally representative sample of adults aged 30 to 79 years through complex, multistage probability sampling. Data were analyzed from April 1 to June 15, 2024., Exposures: The exposures included 5 CKM stages (ie, stages 0-4) reflecting progressive pathophysiology, with advanced (stages 3 or 4) and nonadvanced (stages 0, 1, or 2) disease. CKM stages were defined based on risk factors for metabolic syndrome, cardiovascular disease, and chronic kidney disease., Main Outcome and Measures: The main outcome was the age-standardized prevalence of CKM stages and advanced CKM stages across SDOH, including education, marital status, family income, food security, health insurance, employment, home ownership, and health care access., Results: Among 29 722 participants (weighted mean [SE] age, 50.8 [0.1] years; weighted 50.7% male), the age-standardized prevalence of CKM stages 0 to 4 was 13.6% (95% CI, 13.0%-14.3%), 29.9% (95% CI, 29.1%-30.7%), 43.7% (95% CI, 42.9%-44.5%), 4.7% (95% CI, 4.4%-5.0%), and 8.1% (95% CI, 7.6%-8.5%), respectively. Significant differences were observed in the prevalence of CKM stages across all unfavorable SDOH of interest compared with their favorable counterparts, with unemployment (18.8% [95% CI, 17.7%-20.1%] vs 11.4% [95% CI, 11.0%-11.9%]), low family income (16.1% [95% CI, 15.4%-16.8%] vs 10.1% [95% CI, 9.5%-10.7%]), and food insecurity (18.3% [95% CI, 17.1%-19.6%] vs 11.7% [95% CI, 11.2%-12.2%]) associated with an increased likelihood of advanced CKM stages. Participants with 2 or more unfavorable SDOH were more likely to have advanced CKM stages (age-standardized prevalence, 15.8% [95% CI, 15.2%-16.5%] vs 10.5% [95% CI, 9.9%-11.1%] with <2 unfavorable SDOH). Living in a rented home (15.9% [95% CI, 14.7%-17.0%] vs 9.3% [95% CI, 8.7%-9.9%] owning the home) or not living with a partner (13.2% [95% CI, 12.3%-14.3%] vs 9.2% [95% CI, 8.5%-9.8%] living with a partner) increased the likelihood of advanced CKM stages in female but not male participants., Conclusions and Relevance: In this cross-sectional study, disparities in the prevalence of CKM stages by SDOH, particularly family income, food security, and employment, with notable sex differences, were observed in US adults. These findings highlight the need to address inequities in CKM syndrome through targeted interventions.

Aim: To investigate the safety and efficacy of the application of enhanced recovery after surgery (ERAS) protocols in the perioperative period of abdominal and thoracic localized neuroblastomas (NBs)., Methods: In this retrospective study, 68 children with NBs who underwent surgical resection of the tumor were enrolled. The ERAS protocols for NB excision were implemented in the ERAS group (n = 39) and the consequences were compared with children treated with traditional care (n = 29, TRAD group). The main outcomes of our interest included the incidence of surgery-related complications, the postoperative length of stay (LOS), and the Face/Legs/Activity/Cry/Consolability (FLACC) quantitative table from postoperative days (POD) 1-5. We also evaluated the median intraoperative fluid volume and anesthesia recovery time; blood glucose levels at the beginning of anesthesia, POD1, and 3; WBC counts, CRP values, and the concentration of plasma nutritional indicators on POD1 and 3; time of early ambulation, first anal exhaust, total enteral nutrition (TEN), and discontinue intravenous infusion postoperatively; usage proportion and duration of abdominal and thoracic drainages, nasogastric decompression tubes and urinary catheters; cost of hospitalization, parental satisfaction rate, and readmission rate of surgery ward within 30 days., Results: Compared to the TRAD group, the ERAS group had lower surgery-related complications, albeit not significantly (P > 0.05); the median postoperative LOS decreased from 11.0 to 8.0 days (P < 0.001), the LOS of abdominal NB was significantly shortened (P < 0.001) compared to thoracic NB (P = 0.07) between the two groups; the FLACC scores decreased significantly from POD1-5 (all P < 0.01). The ERAS group had an improved median intraoperative infusion speed (5.0 mL/kg/h vs 8.0 mL/kg/h), time of early ambulation (1.0 days vs 3.0 days), first anal exhaust (2.0 days vs 2.0 days), TEN (5.0 vs 7.0 days), discontinuation of intravenous infusion (5.0 days vs 8.0 days), and total cost of hospitalization (33,897.2 Yuan vs 38,876.3 Yuan); (all P < 0.01). The usage proportion and duration of surgical drainages and tubes were apparently reduced. The mean blood glucose level was higher at the beginning of anesthesia but lower on POD1 and 3 in the ERAS group (P < 0.01). No statistically significant difference was detected in WBC counts and concentrations of hemoglobin and albumin between the two groups of patients (P > 0.05), while the concentrations of prealbumin on POD3 were higher and the CRP level on POD1 was lower in the ERAS group than the TRAD group (P < 0.01). The satisfaction rate of parents was only slightly higher, but the difference was not statistically significant (P = 0.730). No obvious differences were observed in the aspects of NB resection (P = 0.462) and 30-day readmissions of surgery ward (P = 1.000)., Conclusion: The application of ERAS protocols has a significant potential to accelerate perioperative rehabilitation in children undergoing abdominal and thoracic NBs' surgical resection., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In recent years, high-ductility concrete (HDC) has gradually become popular in the construction industry because of its excellent ductility and crack resistance. Concrete itself is a kind of building material with poor tensile properties, and it is necessary to add a large number of steel bars to improve its tensile properties, which increases the construction cost of buildings. However, most of the research studies on high-ductility concrete are scattered. In this paper, the basic mechanical properties of high-ductility concrete and the effects of dry and wet cycles, freeze-thaw cycles, and salt erosion on the durability of high-ductility concrete are obtained by comprehensive analysis. The results show that the tensile properties of HDC can be significantly improved by adding appropriate fiber. When the volume fraction of steel fiber is 2.0%, the splitting tensile strength of concrete is increased by 98.3%. The crack width threshold of concrete chloride erosion is 55-80 μm, and when the crack width threshold is exceeded, the diffusion of CL-1 will be accelerated, and the HDC can control the crack within the threshold, thereby improving the durability of the concrete. Finally, the current research status of high-ductility concrete is analyzed, and the future development of high-ductility concrete is proposed.

Abstract: The liver plays a crucial role in maintaining systemic iron homeostasis by secreting hepcidin, which is essential for coordinating iron levels in the body. Imbalances in iron homeostasis are associated with various clinical disorders related to iron deficiency or iron overload. Despite the clinical significance, the mechanisms underlying how hepatocytes sense extracellular iron levels to regulate hepcidin synthesis and iron storage are not fully understood. In this study, we identified Foxo1, a well-known regulator of macronutrient metabolism, which translocates to the nucleus of hepatocytes in response to high-iron feeding, holo-transferrin, and bone morphogenetic protein 6 (BMP6) treatment. Furthermore, Foxo1 plays a crucial role in mediating hepcidin induction in response to both iron and BMP signals by directly interacting with evolutionally conserved Foxo binding sites within the hepcidin promoter region. These binding sites were found to colocalize with Smad-binding sites. To investigate the physiological relevance of Foxo1 in iron metabolism, we generated mice with hepatocyte-specific deletion of Foxo1. These mice exhibited reduced hepatic hepcidin expression and serum hepcidin levels, accompanied by elevated serum iron and liver nonheme iron concentrations. Moreover, high-iron diet further exacerbated these abnormalities in iron metabolism in mice lacking hepatic Foxo1. Conversely, hepatocyte-specific Foxo1 overexpression increased hepatic hepcidin expression and serum hepcidin levels, thereby ameliorating iron overload in a murine model of hereditary hemochromatosis (Hfe-/- mice). In summary, our study identifies Foxo1 as a critical regulator of hepcidin and systemic iron homeostasis. Targeting Foxo1 may offer therapeutic opportunities for managing conditions associated with aberrant iron metabolism., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Metal halide materials have recently drawn increasing research interest for their excellent opto-electronic properties and structural diversity, but their resulting rigid structures render them brittle and poor formability during manufacturing. Here we demonstrate a thermoplastic luminant hybrid lead halide solid by integrating lead bromide complex into tri-n-octylphosphine oxide (TOPO) matrix. The construction of the hybrid materials can be achieved by a simple dissolution process, in which TOPO molecules act as the solvents and ligands to yield the monodispersed clusters. The combination of these functional units enables the near-room-temperature melt-processing of the materials into targeted geometry by simple molding or printing techniques, which offer possibilities for fluorescent writing inks with outstanding self-healing capacity to physical damage. The intermarriage between metal halide clusters with functional molecules expands the range of practical applications for hybrid metal halide materials., (© 2024 Wiley-VCH GmbH.)

Genomic selection (GS) can accomplish breeding faster than phenotypic selection. Improving prediction accuracy is the key to promoting GS. To improve the GS prediction accuracy and stability, we introduce parallel convolution to deep learning for GS and call it a parallel neural network for genomic selection (PNNGS). In PNNGS, information passes through convolutions of different kernel sizes in parallel. The convolutions in each branch are connected with residuals. Four different L p loss functions train PNNGS. Through experiments, the optimal number of parallel paths for rice, sunflower, wheat, and maize is found to be 4, 6, 4, and 3, respectively. Phenotype prediction is performed on 24 cases through ridge-regression best linear unbiased prediction (RRBLUP), random forests (RF), support vector regression (SVR), deep neural network genomic prediction (DNNGP), and PNNGS. Serial DNNGP and parallel PNNGS outperform the other three algorithms. On average, PNNGS prediction accuracy is 0.031 larger than DNNGP prediction accuracy, indicating that parallelism can improve the GS model. Plants are divided into clusters through principal component analysis (PCA) and K-means clustering algorithms. The sample sizes of different clusters vary greatly, indicating that this is unbalanced data. Through stratified sampling, the prediction stability and accuracy of PNNGS are improved. When the training samples are reduced in small clusters, the prediction accuracy of PNNGS decreases significantly. Increasing the sample size of small clusters is critical to improving the prediction accuracy of GS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xie, Weng, He, Feng, Xu, Ma, Bai and Kong.)

In-service composite laminates are susceptible to impact-induced damage, which can substantially reduce its integrity and service life. The damage prediction remains a great challenge due to mixed damage modes and varying damage patterns. This study develops a novel acoustic emission (AE) energy method for predicting damage areas under three typical damage modes. Laboratory testing of composite laminate specimens subject to quasi-static indentation is performed in conjunction with in-situ AE monitoring to acquire AE data. By bridging two sets of energy formulations developed, namely, the one that correlates the damage area and the released strain energy of each damage mode and another that relates the released strain energy to the AE energy, an analytical model for predicting damage areas using AE energy components is derived. Proper signal procedure procedures are established to extract the energy components from AE monitoring data, and numerical and testing data are used to calibrate the model parameters. The effectiveness of the proposed model is further validated by comparing the prediction results of the damage areas with the actual damage areas of specimens tested under different indentation depths. The result indicates that the proposed AE energy method can yield reliable predictions of the damage area under mixed damage modes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

High serum urate levels are the major risk factor for gout. URAT1, the primary transporter for urate absorption in the kidneys, is well known as an anti-hyperuricemia drug target. However, the clinical application of URAT1-targeted drugs is limited because of their low specificity and severe side effects. The lack of structural information impedes elucidation of the transport mechanism and the development of new drugs. Here, we present the cryoelectron microscopy (cryo-EM) structures of human URAT1(R477S), its complex with urate, and its closely related homolog OAT4. URAT1(R477S) and OAT4 exhibit major facilitator superfamily (MFS) folds with outward- and inward-open conformations, respectively. Structural comparison reveals a 30° rotation between the N-terminal and C-terminal domains, supporting an alternating access mechanism. A conserved arginine (OAT4-Arg473/URAT1-Arg477) is found to be essential for chloride-mediated inhibition. The URAT1(R477S)-urate complex reveals the specificity of urate recognition. Taken together, our study promotes our understanding of the transport mechanism and substrate selection of URAT1., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Genetically engineered mouse models (GEMMs) are vital for elucidating gene function and disease mechanisms. An overwhelming number of GEMM lines have been generated, but endeavors to collect and organize the information of these GEMMs are seriously lagging behind. Only a few databases are developed for the information of current GEMMs, and these databases lack biological descriptions of allele compositions, which poses a challenge for nonexperts in mouse genetics to interpret the genetic information of these mice. Moreover, these databases usually do not provide information on human diseases related to the GEMM, which hinders the dissemination of the insights the GEMM provides as a human disease model. To address these issues, we developed an algorithm to annotate all the allele compositions that have been reported with Python programming and have developed the genetically modified mice information database (GMMID; http://www.gmmid.cn), a user-friendly database that integrates information on GEMMs and related diseases from various databases, including National Center for Biotechnology Information, Mouse Genome Informatics, Online Mendelian Inheritance in Man, International Mouse Phenotyping Consortium, and Jax lab. GMMID provides comprehensive genetic information on >70 055 alleles, 65 520 allele compositions, and ∼4000 diseases, along with biologically meaningful descriptions of alleles and allele combinations. Furthermore, it provides spatiotemporal visualization of anatomical tissues mentioned in these descriptions, shown alongside the allele compositions. Compared to existing mouse databases, GMMID considers the needs of researchers across different disciplines and presents obscure genetic information in an intuitive and easy-to-understand format. It facilitates users in obtaining complete genetic information more efficiently, making it an essential resource for cross-disciplinary researchers. Database URL: http://www.gmmid.cn., (© The Author(s) 2024. Published by Oxford University Press.)

Risk prediction tools for colorectal cancer (CRC) have potential to improve the efficiency of population-based screening by facilitating risk-adapted strategies. However, such an applicable tool has yet to be established in the Chinese population. In this study, a risk score was created using data from the China Kadoorie Biobank (CKB), a nationwide cohort study of 409,854 eligible participants. Diagnostic performance of the risk score was evaluated in an independent CRC screening programme, which included 91,575 participants who accepted colonoscopy at designed hospitals in Zhejiang Province, China. Over a median follow-up of 11.1 years, 3136 CRC cases were documented in the CKB. A risk score was created based on nine questionnaire-derived variables, showing moderate discrimination for 10-year CRC risk (C-statistic = 0.68, 95 % CI: 0.67-0.69). In the CRC screening programme, the detection rates of CRC were 0.25 %, 0.82 %, and 1.93 % in low-risk (score <6), intermediate-risk (score: 6-19), and high-risk (score >19) groups, respectively. The newly developed score exhibited a C-statistic of 0.65 (95 % CI: 0.63-0.66), surpassing the widely adopted tools such as the Asia-Pacific Colorectal Screening (APCS), modified APCS, and Korean Colorectal Screening scores (all C-statistics = 0.60). In conclusion, we developed a novel risk prediction tool that is useful to identify individuals at high risk of CRC. A user-friendly online calculator was also constructed to encourage broader adoption of the tool., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Low-density lipoprotein cholesterol (LDL-C) and type 2 diabetes (T2DM) are both independent risk factors for aortic stenosis (AS). In AS patients, whether LDL-C or T2DM is associated with fast AS progression (FASP) and their interaction is unknown. This study aims to test the hypothesis that there is a heightened risk of FASP when elevated LDL-C coexists with T2DM., Methods: The Real-world Data of Cardiometabolic Protections (RED-CARPET) study enrolled participants with mild (peak aortic velocity = 2-3 m/s), moderate (3-4 m/s) and severe ( ≥ 4 m/s) AS between January 2015 and December 2020 at a single center. Participants were further stratified by baseline LDL-C joint T2DM, follow-up echocardiography was performed after 6 months, and the primary outcome was FASP, defined as the annual change in aortic peak velocity ( ≥ 0.3 m/s/year)., Results: Among the 170 participants included, 45.3% had mild AS, 41.2% had moderate AS, and 13.5% had severe AS. The mean age was 66.84 ± 12.64 years, and 64.1% were women. During the follow-up period of 2.60 ± 1.43 years, 35 (20.6%) cases of FASP were identified. Using non-T2DM with LDL-C < 2.15 mmol/L as reference, FASP risk was 1.30 [odds ratio (OR), 95% CI (0.99-7.78, p = 0.167)] for non-T2DM with LDL-C 2.15-3.14 mmol/L, 1.60 [OR, 95% CI (1.17-3.29, p = 0.040)] for non-T2DM with LDL-C ≥ 3.14 mmol/L, 2.21 [OR, 95% CI (0.49-4.32, p = 0.527)] for T2DM with LDL-C < 2.15 mmol/L, 2.67 [OR, 95% CI (1.65-7.10, p = 0.004)] for T2DM with LDL-C 2.15-3.14 mmol/L, and 3.20 [OR, 95% CI (1.07-5.34, p = 0.022)] for T2DM with LDL-C ≥ 3.14 mmol/L., Conclusions: LDL-C joint T2DM was associated with FASP. This investigation suggests that fast progression of AS may develop if LDL-C is poorly managed in T2DM. Additional research is needed to validate this finding and explore the possible biological mechanism to improve the cardiometabolic management of T2DM and seek possible prevention for AS progression for this population., Clinical Trial Registration: ChiCTR2000039901 (https://www.chictr.org.cn)., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

The application of carbon fiber in cement matrix has some disadvantages, such as poor dispersion and poor interfacial adhesion. In order to improve the interaction between carbon fiber and cement matrix and improve the properties of cement-based composites, carbon fiber was modified by electrophoretic deposition of nano-graphene oxide (GO). In this paper, the effects of doping CF into the cement matrix before and after GO modification are studied comparatively in terms of electrical conductivity, electrothermal warming effect, and pressure-sensitive properties of the cement matrix. It was found that the GO-modified CF reduces both the electrical resistivity of cementitious composites and the required level of fiber incorporation compared to CF. The percolation threshold is 0.7 wt% for CF and 0.5 wt% for GO-CF. The GO-modified CF is more effective than CF as a conductive filler to enhance the electrothermal warming performance of the cement matrix. When the GO-CF doping rate is 0.5%, the specimen temperature increases most rapidly, and the temperature rise value reaches a maximum of up to 30.45 °C, which is twice that of the CF group. When the fiber content is 0.7%, the pressure sensitivity of the sample was the best. When the fiber content is 0.5%, GO-CF can improve the pressure sensitivity of cement mortar specimens, and increase the resistance change rate of the cement mortar specimens by 5.7%.

Fiber concrete exhibits superior performance in various aspects compared to plain concrete and has been widely researched and applied worldwide. However, many industrially made fibers are expensive, and their cost has to be considered before use; thus, it would be economically valuable to find inexpensive fibers with excellent properties to make fiber concrete. Rural areas have many rich straw resources to be disposed of; at the same time, the rapid development of the automobile industry has introduced a large number of used tires containing steel wire with a very low reuse rate. These two low-cost materials can be processed to make fibers, making the study of mechanical properties regarding their incorporation into concrete practically significant for reducing the cost of fiber concrete. Based on this, a three-factor, three-level orthogonal test was conducted to investigate the effects of different dosages of corn straw fibers and scrap steel fibers, as well as the water-cement ratio, on the mechanical properties of concrete. The optimum level of each factor for blended straw-waste-steel-fiber concrete with different mechanical properties was obtained using the polar and ANOVA methods. It was found that the compressive strength, splitting tensile strength, flexural strength, and impact resistance of the specimens after fiber dosing were better than those of plain concrete specimens with the same water-cement ratio. The maximum improvement was 14.96% in cubic compressive strength, 42.90% in tensile strength, and 16.30% in flexural strength, while the maximum improvement in impact energy consumption at the final crack was 228.03%. Combined with SEM microanalysis, the two fibers formed a stronger whole with the C-S-H gel. When the specimen was subjected to load, the two fibers were able to withstand part of the load, thus enhancing the load-bearing capacity. Finally, the optimal mix ratio of blended straw-scrap-steel-fiber concrete was determined to be 0.8% corn straw fibers by volume, 0.6% scrap steel fibers by volume, and a 0.45 water-cement ratio by combining the weights of the levels of each factor under its four different mechanical properties through hierarchical analysis. This analysis of mechanical properties provides a reference for practical applications in future projects.

Background: Uncertainties still existed about the effect of high-quality protein supplementation on cardiovascular disease (CVD) risk factors, although high-quality proteins such as soy and milk proteins have proposed to be beneficial for cardiometabolic health., Methods: A systematic search in PubMed, Web of Science, Cochrane Library, Scopus, and Embase was conducted to quantify the impact of high-quality protein on CVD risk factors., Results: 63 RCTs on 4 types of high-quality protein including soy protein, milk protein, whey, and casein were evaluated. Soy protein supplementation decreased systolic blood pressure (SBP, -1.42 [-2.68, -0.17] mmHg), total cholesterol (TC, -0.18 [-0.30, -0.07] mmol/L), and low-density lipoprotein cholesterol (LDL-C, -0.16 [-0.27, -0.05] mmol/L). Milk protein supplementation decreased SBP (-2.30 [-3.45, -1.15] mmHg) and total cholesterol (-0.27 [-0.51, -0.03] mmol/L). Whey supplementation decreased SBP (-2.20 [-3.89, -0.51] mmHg), diastolic blood pressure (DBP, -1.07 [-1.98, -0.16] mmHg), triglycerides (-0.10 [-0.17, -0.03] mmol/L), TC (-0.18 [-0.35, -0.01] mmol/L), LDL-C (-0.09 [-0.16, -0.01] mmol/L) and fasting blood insulin (FBI, -2.02 [-3.75, -0.29] pmol/L). Casein supplementation decreased SBP (-4.10 [-8.05, -0.14] mmHg). In the pooled analysis of four high-quality proteins, differential effects were seen in individuals with different health status. In hypertensive individuals, high-quality proteins decreased both SBP (-2.69 [-3.50, -1.87] mmHg) and DBP (-1.34 [-2.09, -0.60] mmHg). In overweight/obese individuals, high-quality proteins improved SBP (-1.40 [-2.22, -0.59] mmHg), DBP (-2.59 [-3.20, -1.98] mmHg), triglycerides (-0.09 [-0.15, -0.02] mmol/L), TC (-0.14 [-0.22, -0.05] mmol/L), LDL-C (-0.12 [-0.16, -0.07] mmol/L), and HDL-C levels (0.02 [0.01, 0.04] mmol/L). According to the benefits on CVD risks factors, whey ranked top for improving cardiometabolic health in hypertensive or overweight/obese individuals., Conclusion: Our study supports a beneficial role of high-quality protein supplementation to reduce CVD risk factors. Further studies are still warranted to investigate the effects of different high-quality proteins on CVD risks in individuals with cardiometabolic disorders., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Grain size is one of the key microstructural factors affecting the mechanical properties of polycrystalline metal materials. In this study, a novel method for grain size evaluation using ultrasonic coda waves is proposed. Different from conventional bulk wave methods that require a point-by-point scanning of the structure, the proposed method allows for a rapid evaluation of the average grain size of the whole part from a single inspection location using one-pass testing data. A piecewise energy attenuation function dealing with different attenuation mechanisms is proposed to obtain the effective attenuation coefficient of coda waves. A power-law model is constructed to correlate the effective attenuation coefficient with the average grain size. Ultrasonic testing on nickel-based superalloy plate specimens with different average grain sizes is performed for model calibration and method verification. The applicability and robustness of the proposed method are further validated using a realistic turbine disk specimen with an irregular shape and non-uniform grain sizes. Results show that the proposed method yields a reliable and accurate estimation of the average grain size with a maximum relative error less than 20 %., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The use of synbiotics is emerging as a promising intervention strategy for regulating the gut microbiota and for preventing or reducing obesity, in comparison with the use of probiotics or prebiotics alone. A previous in vivo study revealed that Lacticaseibacillus paracasei K56 (L. paracasei K56) could alleviate obesity induced in high-fat-diet mice; however, the effect of the synbiotic combination of L. paracasei K56 and prebiotics in obese individuals has not been explored fully., Results: The effect of prebiotics on the proliferation of L. paracasei K56 was determined by spectrophotometry. The results showed that polydextrose (PG), xylooligosaccharide (XOS), and galactooligosaccharide (GOS) had a greater potential to be used as substrates for L. paracasei K56 than three other prebiotics (melitose, stachyose, and mannan-oligosaccharide). An in vitro fermentation model based on the feces of ten obese female volunteers was then established. The results revealed that K56&#95;GOS showed a significant increase in GOS degradation rate and short-chain fatty acid (SCFA) content, and a decrease in gas levels, compared with PG, XOS, GOS, K56&#95;PG, and K56&#95;XOS. Changes in these microbial biomarkers, including a significant increase in Bacteroidota, Bifidobacterium, Lactobacillus, Faecalibacterium, and Blautia and a decrease in the Firmicutes/Bacteroidota ratio and Escherichia-Shigella in the K56&#95;GOS group, were associated with increased SCFA content and decreased gas levels., Conclusion: This study demonstrates the effect of the synbiotic combination of L. paracasei K56 and GOS on obese individuals and indicates its potential therapeutic role in obesity treatment. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The pod and seed counts are important yield-related traits in soybean. High-precision soybean breeders face the major challenge of accurately phenotyping the number of pods and seeds in a high-throughput manner. Recent advances in artificial intelligence, especially deep learning (DL) models, have provided new avenues for high-throughput phenotyping of crop traits with increased precision. However, the available DL models are less effective for phenotyping pods that are densely packed and overlap in in situ soybean plants; thus, accurate phenotyping of the number of pods and seeds in soybean plant is an important challenge. To address this challenge, the present study proposed a bottom-up model, DEKR-SPrior (disentangled keypoint regression with structural prior), for in situ soybean pod phenotyping, which considers soybean pods and seeds analogous to human people and joints, respectively. In particular, we designed a novel structural prior (SPrior) module that utilizes cosine similarity to improve feature discrimination, which is important for differentiating closely located seeds from highly similar seeds. To further enhance the accuracy of pod location, we cropped full-sized images into smaller and high-resolution subimages for analysis. The results on our image datasets revealed that DEKR-SPrior outperformed multiple bottom-up models, viz., Lightweight-OpenPose, OpenPose, HigherHRNet, and DEKR, reducing the mean absolute error from 25.81 (in the original DEKR) to 21.11 (in the DEKR-SPrior) in pod phenotyping. This paper demonstrated the great potential of DEKR-SPrior for plant phenotyping, and we hope that DEKR-SPrior will help future plant phenotyping., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Jingjing He et al.)

Anthocyanins and proanthocyanidins are considered to be essential secondary metabolites in grapes and are used to regulate metabolic processes, while miRNAs are involved in their synthesis of anthocyanins and proanthocyanidins to regulate metabolic processes. The present research work was carried out to investigate the underlying regulatory mechanism of target genes in the grape cultivars 'Italia' and 'Benitaka'. miRNA and transnscriptomic sequencing technology were employed to characterize both the profiles of miRNAs and the transcripts of grape peels at 10 and 11 weeks post flowering (10 wpf and 11 wpf). The results revealed that the expression level of vvi-miR828a in 'Italia' at 10 and 11 wpf was significantly higher than that in 'Benitaka'. miRNA-seq analysis predicted MYBPA1 to be the target gene of vvi-miR828a. In transcriptome analysis, the expression level of the VvMYBPA1 gene in 'Benitaka' was significantly higher than that in 'Italia'; in addition, the TPM values (expression levels) of VvMYBPA1 and miR828a also showed an evident negative correlation. The determination of the proanthocyanidin (PA) content in 'Italia' and 'Benitaka' peels at 11 wpf demonstrated that the PA content of 'Benitaka' was significantly higher than that of 'Italia'. The outcomes of RT-qRCR analysis exhibited that the expression levels of the VdPAL , VdCHS , VdCHI , VdDFR , VdMYB5b , VdANR , and VdMYBPA1 genes related anthocyanin and proanthocyanidin pathways were reduced, while the expression levels of all of the above genes were increased after the transient expression of the VvMYBPA1 vector into grape leaves. The results of the transient overexpression experiment of vvi-miR828a before the veraison period of strawberry fruits showed that vvi-miR828a can significantly slow down the coloration of strawberries. The vvi-miR828a negatively regulates the accumulation of proanthocyanidins in grape fruits by inhibiting the expression of VvMYBPA1 .

Traumatic Brain Injury (TBI) represents a significant public health challenge. Recovery from brain injury necessitates the collaborative efforts of various resident neural cells, predominantly microglia. The present study analyzed rat and mouse RNA expression micro‑arrays, high‑throughput RNA sequencing and single‑cell sequencing data sourced from public databases. To construct an inflammation regulation network around TYRO protein tyrosine kinase‑binding protein (TYROBP), to evaluate the role of TYROBP in cell death after TBI. These findings indicate that following TBI, neurons predominantly communicate with one another through the CXC chemokine ligand (CXCL) and CC chemokine ligand (CCL) signaling pathways, employing a paracrine mechanism to activate microglia. These activated microglia intensify the pathological progression of brain injury by releasing factors such as tumor necrosis factor α (TNF‑α), vascular endothelial growth factor and transforming growth factor β via the NF‑κB pathway. Cells co‑culture experiments demonstrated that neurons, impaired by mechanical injury, interact with microglia through non‑contact mechanisms. Activated microglia secrete cytokines, including TNF‑α, CXCL‑8 and CCL2, which trigger an inflammatory response and facilitate neuronal apoptosis. TYROBP gene knockout in microglia was demonstrated to reduce this interaction and reduce neuronal cell apoptosis rates.

Probiotics have garnered increasing attention as a potential therapeutic approach for type 2 diabetes mellitus (T2DM). Previous studies have confirmed that Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup) could stimulate the secretion of glucagon-like peptide-1 (GLP-1) in NCI-H716 cells, but whether MN-Gup has a hypoglycemic effect on T2DM in vivo remains unclear. In this study, a T2DM mouse model was constructed, with a high-fat diet and streptozotocin in mice, to investigate the effect of MN-Gup on diabetes. Then, different doses of MN-Gup (2 × 10 9 CFU/kg, 1 × 10 10 CFU/kg) were gavaged for 6 weeks to investigate the effect of MN-Gup on glucose metabolism and its potential mechanisms. The results showed that a high-dose of MN-Gup significantly reduced the fasting blood glucose (FBG) levels and homeostasis model assessment-insulin resistance (HOMA-IR) of T2DM mice compared to the other groups. In addition, there were significant increases in the short-chain fatty acids (SCFAs), especially acetate, and GLP-1 levels in the MN-Gup group. MN-Gup increased the relative abundance of Bifidobacterium and decreased the number of Escherichia-Shigella and Staphylococcus . Moreover, the correlation analysis revealed that Bifidobacterium demonstrated a significant positive correlation with GLP-1 and a negative correlation with the incremental AUC. In summary, this study demonstrates that Bifidobacterium animalis subsp. lactis MN-Gup has significant hypoglycemic effects in T2DM mice and can modulate the gut microbiota, promoting the secretion of SCFAs and GLP-1.

Hierarchical-porous-structured materials have been widely used in the field of electromagnetic wave (EMW) absorption, playing a critical role in minimizing EMW interference and pollution. High-quality EMW absorbers, characterized by a lower thickness, lighter weight, wider absorption band, and stronger absorption capacity, have been instrumental in reducing damage and preventing malfunctions in the automotive and aviation industries. The utilization of discarded nut shells through recycling can not only alleviate environmental problems but relieve resource constraints. Herein, a facile method for the preparation of hierarchical porous biomass carbon derived from abandoned Xanthoceras Sorbifolium Bunge Shell (XSS) biomass was developed for high-performance EMW absorption. The porous structures of XSS biochar were studied by using different levels of the K 2 CO 3 activator and simple carbonization. The effect of K 2 CO 3 on the EMW parameters, including the complex permittivity, complex permeability, polarization relaxation, and impedance matching, was analyzed. The best EMW absorption performance of the XSS biochar was observed at a mass ratio of activator-to-biomass of 2:1. A minimum reflection loss (RL min ) of -38.9 dB was achieved at 9.12 GHz, and a maximum effective absorption bandwidth (EAB max ) of up to 3.28 GHz (14.72~18.0 GHz) could be obtained at a 1.8 mm thickness. These results demonstrated that hierarchical porous XSS carbon was prepared successfully. Simultaneously, the prepared XSS biochar was confirmed as a potential and powerfully attractive EMW-absorbing material. The proposal also provided a simple strategy for the development of a green, low-cost, and sustainable biochar as a lightweight high-performance absorbing material.

Background: Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa. However, few studies focus on the distributional characteristics of allergens in AR patients in Southern Fujian Province, China., Methods: A skin prick test (SPT) was performed and eight common allergens including Dermatophagoides farinae ( Df), Dermatophagoides pteronyssinus ( Dpt ), weeds, animal dander, molds, cockroaches, and mangoes were chosen., Results: The positive reactions rate to the allergens was 65.79% in 6689 patients in Southern Fujian Province. Positive reactions to Df and Dpt had a negative association with age, whereas positive reactions to cockroach and weed had a positive association with age. A linear trend analysis demonstrated a significant positive relationship between positive reactions to various allergens from 2016 to 2019. Positive reactions to Df and Dpt were both correlated with the season. Positive reactions to Df, Dpt , cockroach and weed were related to disease duration and positive reactions to cockroach were correlated with city residence. Multivariate analysis revealed that male positive reactions gradually decreased with age (≤ 60), in contrast to female (≤ 60) positive reactions. Statistical difference was observed between the genders with regard to AR incidence from 2016 to 2019. The positive rate of skin tests was highest in summer in men, whereas in women it was lowest in summer. The gender composition ratios of positive cases in Xiamen, Zhangzhou, and Quanzhou cities differed significantly. The proportion of patients with positive reactions to the allergens in the three cities decreased with age. The highest proportions of patients with positive reactions all occurred during summer in the three cities. Furthermore, there were statistically significant differences in the age composition ratios across the seasons., Conclusion: This study analyzed the distributional characteristics of AR allergens in Southern Fujian Province, China. These findings will inform specific immunotherapy for AR patients., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024 He et al.)

Key Message: Residual neural network genomic selection is the first GS algorithm to reach 35 layers, and its prediction accuracy surpasses previous algorithms. With the decrease in DNA sequencing costs and the development of deep learning, phenotype prediction accuracy by genomic selection (GS) continues to improve. Residual networks, a widely validated deep learning technique, are introduced to deep learning for GS. Since each locus has a different weighted impact on the phenotype, strided convolutions are more suitable for GS problems than pooling layers. Through the above technological innovations, we propose a GS deep learning algorithm, residual neural network for genomic selection (ResGS). ResGS is the first neural network to reach 35 layers in GS. In 15 cases from four public data, the prediction accuracy of ResGS is higher than that of ridge-regression best linear unbiased prediction, support vector regression, random forest, gradient boosting regressor, and deep neural network genomic prediction in most cases. ResGS performs well in dealing with gene-environment interaction. Phenotypes from other environments are imported into ResGS along with genetic data. The prediction results are much better than just providing genetic data as input, which demonstrates the effectiveness of GS multi-modal learning. Standard deviation is recommended as an auxiliary GS evaluation metric, which could improve the distribution of predicted results. Deep learning for GS, such as ResGS, is becoming more accurate in phenotype prediction., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The valley polarization, induced by the magnetic proximity effect, in monolayer transition metal dichalcogenides (TMDCs), has attracted significant attention due to the intriguing fundamental physics. However, the enhancement and modulation of valley polarization for real device applications is still a challenge. Here, using first-principles calculations we investigate the valley polarization properties of monolayer TMDCs CrS 2 and CrSe 2 and how to enhance the valley polarization by constructing Janus CrSSe (with an internal electric field) and modulate the polarization in CrSSe by applying external electric fields. Janus CrSSe exhibits inversion symmetry breaking, internal electric field, spin-orbit coupling, and compelling spin-valley coupling. A magnetic substrate of the MnO 2 monolayer can induce a modest magnetic moment in CrSe 2 , CrSe 2 , and CrSSe. Notably, the Janus structure with an internal electric field has a much larger valley p compared with its non-Janus counterparts. Moreover, the strength of valley polarization can be further modulated by applying external electric fields. These findings suggest that Janus materials hold promise for designing and developing advanced valleytronic devices.

Background: Diabetic cardiomyopathy (DCM) is a serious health-threatening complication of diabetes mellitus characterized by myocardial fibrosis and abnormal cardiac function. Human umbilical cord mesenchymal stromal cells (hUC-MSCs) are a potential therapeutic tool for DCM and myocardial fibrosis via mechanisms such as the regulation of microRNA (miRNA) expression and inflammation. It remains unclear, however, whether hUC-MSC therapy has beneficial effects on cardiac function following different durations of diabetes and which mechanistic aspects of DCM are modulated by hUC-MSC administration at different stages of its development. This study aimed to investigate the therapeutic effects of intravenous administration of hUC-MSCs on DCM following different durations of hyperglycemia in an experimental male model of diabetes and to determine the effects on expression of candidate miRNAs, target mRNA and inflammatory mediators., Methods: A male mouse model of diabetes was induced by multiple low-dose streptozotocin injections. The effects on severity of DCM of intravenous injections of hUC-MSCs and saline two weeks previously were compared at 10 and 18 weeks after diabetes induction. At both time-points, biochemical assays, echocardiography, histopathology, polymerase chain reaction (PCR), immunohistochemistry and enzyme-linked immunosorbent assays (ELISA) were used to analyze blood glucose, body weight, cardiac structure and function, degree of myocardial fibrosis and expression of fibrosis-related mRNA, miRNA and inflammatory mediators., Results: Saline-treated diabetic male mice had impaired cardiac function and increased cardiac fibrosis after 10 and 18 weeks of diabetes. At both time-points, cardiac dysfunction and fibrosis were improved in hUC-MSC-treated mice. Pro-fibrotic indicators (α-SMA, collagen I, collagen III, Smad3, Smad4) were reduced and anti-fibrotic mediators (FGF-1, miRNA-133a) were increased in hearts of diabetic animals receiving hUC-MSCs compared to saline. Increased blood levels of pro-inflammatory cytokines (IL-6, TNF, IL-1β) and increased cardiac expression of IL-6 were also observed in saline-treated mice and were reduced by hUC-MSCs at both time-points, but to a lesser degree at 18 weeks., Conclusion: Intravenous injection of hUC-MSCs ameliorated key functional and structural features of DCM in male mice with diabetes of shorter and longer duration. Mechanistically, these effects were associated with restoration of intra-myocardial expression of miRNA-133a and its target mRNA COL1AI as well as suppression of systemic and localized inflammatory mediators., (© 2024. The Author(s).)

The use of seawater and sea sand as replacements for fresh water and river sand in the preparation of seawater and sea sand concrete can effectively address issues such as high transportation costs, extended construction periods, and resource wastage. Nevertheless, in northern coastal areas, the problem of concrete durability in the complex and changing marine environment is more prominent. Research on the durability of seawater sea sand concrete is beneficial to the widening of its application range. To investigate the impact of glass fiber (GF) and polyvinyl alcohol fiber (PVA) with different blending methods on the seawater freeze-thaw resistance of seawater sea sand concrete (SSC), corresponding specimens were prepared, and seawater freeze-thaw cycling tests were conducted. By adopting the slow-freezing method and combining macro-structure and micro-morphology, the damage mechanism and the deterioration law of fiber-reinforced SSC under seawater freezing and thawing were investigated. The results indicate that, macroscopically, the incorporation of GF and PVA can effectively mitigate the damage to the matrix and reduce the effects of external erosive substances on the rate of strength loss, the rate of mass loss, and the relative dynamic elastic modulus. After 75 cycles, the SSC with a total volume doping of 0.3% and a blending ratio of 1:1 showed a 41.23% and 27.55% reduction in mass loss and strength loss, respectively, and a 29.9% improvement in relative dynamic elastic modulus compared with the basic group. Microscopic analysis reveals that the combined effect of freezing and expansion forces, the expansive substances generated by seawater intrusion into the interior of the matrix, and salt crystallization all weaken the bond between aggregate and mortar, leading to accelerated deterioration of the concrete. The incorporation of fibers enables the matrix to become denser and improves its crack-resistant properties, resulting in a better durability than that of the basic group. The damage prediction model established by the NSGM(1,N) model of gray system theory exhibits high accuracy and is suitable for long-term prediction, accurately predicting the damage of seawater sea sand concrete under seawater freeze-thaw coupling.

The rate of soybean canopy establishment largely determines photoperiodic sensitivity, subsequently influencing yield potential. However, assessing the rate of soybean canopy development in large-scale field breeding trials is both laborious and time-consuming. High-throughput phenotyping methods based on unmanned aerial vehicle (UAV) systems can be used to monitor and quantitatively describe the development of soybean canopies for different genotypes. In this study, high-resolution and time-series raw data from field soybean populations were collected using UAVs. The RGB (red, green, and blue) and infrared images are used as inputs to construct the multimodal image segmentation model-the RGB & Infrared Feature Fusion Segmentation Network (RIFSeg-Net). Subsequently, the segment anything model was employed to extract complete individual leaves from the segmentation results obtained from RIFSeg-Net. These leaf aspect ratios facilitated the accurate categorization of soybean populations into 2 distinct varieties: oval leaf type variety and lanceolate leaf type variety. Finally, dynamic modeling was conducted to identify 5 phenotypic traits associated with the canopy development rate that differed substantially among the classified soybean varieties. The results showed that the developed multimodal image segmentation model RIFSeg-Net for extracting soybean canopy cover from UAV images outperformed traditional deep learning image segmentation networks (precision = 0.94, recall = 0.93, F1-score = 0.93). The proposed method has high practical value in the field of germplasm resource identification. This approach could lead to the use of a practical tool for further genotypic differentiation analysis and the selection of target genes., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Hui Yu et al.)

Background: Spinal cord injury (SCI) is a serious clinical condition that has pathological changes such as increased neuroinflammation and nerve tissue damage, which eventually manifests as fibrosis of the injured segment and the development of a spinal cord cavity leading to loss of function. Cell-based therapy, such as mesenchymal stem cells (MSCs) and neural stem cells (NSCs) are promising treatment strategies for spinal cord injury via immunological regulation and neural replacement respectively. However, therapeutic efficacy is rare reported on combined transplantation of MSC and NSC in acute mice spinal cord injury even the potential reinforcement might be foreseen. Therefore, this study was conducted to investigate the safety and efficacy of co-transplanting of MSC and NSC sheets into an SCI mice model on the locomotor function and pathological changes of injured spinal cord., Methods: To evaluate the therapeutic effects of combination cells, acute SCI mice model were established and combined transplantation of hiPSC-NSCs and hMSCs into the lesion site immediately after the injury. Basso mouse scale was used to perform the open-field tests of hind limb motor function at days post-operation (dpo) 1, 3, 5, and 7 after SCI and every week after surgery. Spinal cord and serum samples were collected at dpo 7, 14, and 28 to detect inflammatory and neurotrophic factors. Hematoxylin-eosin (H&E) staining, masson staining and transmission electron microscopy were used to evaluate the morphological changes, fibrosis area and ultrastructure of the spinal cord., Result: M&N transplantation reduced fibrosis formation and the inflammation level while promoting the secretion of nerve growth factor and brain-derived neurotrophic factor. We observed significant reduction in damaged tissue and cavity area, with dramatic improvement in the M&N group. Compared with the Con group, the M&N group exhibited significantly improved behaviors, particularly limb coordination., Conclusion: Combined transplantation of hiPSC-NSC and hMSC could significantly ameliorate neuroinflammation, promote neuroregeneration, and decrease spinal fibrosis degree in safe and effective pattern, which would be indicated as a novel potential cell treatment option., (© 2024. The Author(s).)

Background and Aims: Mesenchymal stromal cells (MSCs) a potentially effective disease-modulating therapy for diabetic nephropathy (DN) but their clinical translation has been hampered by incomplete understanding of the optimal timing of administration and in vivo mechanisms of action. This study aimed to elucidate the reno-protective potency and associated mechanisms of single intravenous injections of human umbilical cord-derived MSCs (hUC-MSCs) following shorter and longer durations of diabetes., Methods: A streptozotocin (STZ)-induced model of diabetes and DN was established in C57BL/6 mice. In groups of diabetic animals, human (h)UC-MSCs or vehicle were injected intravenously at 8 or 16 weeks after STZ along with vehicle-injected non-diabetic animals. Diabetes-related kidney abnormalities was analyzed 2 weeks later by urine and serum biochemical assays, histology, transmission electron microscopy and immunohistochemistry. Serum concentrations of pro-inflammatory and pro-fibrotic cytokines were quantified by ELISA. The expression of autophagy-related proteins within the renal cortices was investigated by immunoblotting. Bio-distribution of hUC-MSCs in kidney and other organs was evaluated in diabetic mice by injection of fluorescent-labelled cells., Results: Compared to non-diabetic controls, diabetic mice had increases in urine albumin creatinine ratio (uACR), mesangial matrix deposition, podocyte foot process effacement, glomerular basement membrane thickening and interstitial fibrosis as well as reduced podocyte numbers at both 10 and 18 weeks after STZ. Early (8 weeks) hUC-MSC injection was associated with reduced uACR and improvements in multiple glomerular and renal interstitial abnormalities as well as reduced serum IL-6, TNF-α, and TGF-β1 compared to vehicle-injected animals. Later (16 weeks) hUC-MSC injection also resulted in reduction of diabetes-associated renal abnormalities and serum TGF-β1 but not of serum IL-6 and TNF-α. At both time-points, the kidneys of vehicle-injected diabetic mice had higher ratio of p-mTOR to mTOR, increased abundance of p62, lower abundance of ULK1 and Atg12, and reduced ratio of LC3B to LC3A compared to non-diabetic animals, consistent with diabetes-associated suppression of autophagy. These changes were largely reversed in the kidneys of hUC-MSC-injected mice. In contrast, neither early nor later hUC-MSC injection had effects on blood glucose and body weight of diabetic animals. Small numbers of CM-Dil-labeled hUC-MSCs remained detectable in kidneys, lungs and liver of diabetic mice at 14 days after intravenous injection., Conclusions: Single intravenous injections of hUC-MSCs ameliorated glomerular abnormalities and interstitial fibrosis in a mouse model of STZ-induced diabetes without affecting hyperglycemia, whether administered at relatively short or longer duration of diabetes. At both time-points, the reno-protective effects of hUC-MSCs were associated with reduced circulating TGF-β1 and restoration of intra-renal autophagy., (© 2024. The Author(s).)

Attention deficit hyperactivity disorder (ADHD) is commonly accompanied by learning and memory deficits. This study aimed to demonstrate the effects of probiotic Bifidobacterium animalis subsp. lactis A6 (BAA6) on behaviour and memory function in spontaneously hypertensive rats (SHRs). The results showed that BAA6 treatment ameliorated spatial working memory deficits and inhibited hippocampal neuron loss in SHRs. The levels of neurotransmitters such as acetylcholine, dopamine, and norepinephrine, and the brain derived neurotrophic factor increased and that of glutamate decreased in the brain tissue of SHRs after BAA6 administration. Moreover, BAA6 reduced the levels of pro-inflammatory cytokines TNF-α and IL-1β, and increased the levels of anti-inflammatory IL-10 and antioxidant glutathione in SHRs. 16S rRNA high-throughput sequencing showed that BAA6 treatment changed the gut microbiota composition. BAA6 promoted beneficial Lactobacillus , Romboutsia , Blautia , and Turicibacter , and decreased the enrichment of bacterial genera such as Dietzia , Sporosarcina , Brevibacterium , NK4A214 &#95;group, Atopostipes , and Facklamia negatively associated with neurotransmitter release and anti-inflammatory effects in SHRs. Together, these results suggested that BAA6 improved memory function by ameliorating hippocampal damage, abnormal neurotransmitter release and cerebral inflammation by reshaping the gut microbiota in SHRs. This study provides a scientific basis for the development and application of BAA6 as a promising dietary intervention to reduce the risk of ADHD.

High-efficacy recycling of spent lithium cobalt oxide (LiCoO 2 ) batteries is one of the key tasks in realizing a global resource security strategy due to the rareness of lithium (Li) and cobalt (Co) resources. However, it is of great significance to develop the innovative recycle methods for spent LiCoO 2 , simultaneously realizing the efficient recovery of valuable elements and the regeneration of high-performance LiCoO 2 . Herein, a novel strategy of regenerating LiCoO 2 cathode is proposed, which involves the preparation of micro-spherical aluminum (Al)-doped lithium-lacked precursor (Li 2x Co 1-x-y Al 2/3y CO 3, remarked as "PLCAC") via ammonium bicarbonate coprecipitation. The comprehensive conditions affecting particle growth kinetics, morphology and particle size the has been investigated in detail by physical characterizations and electrochemical measurements. And the optimized Al-doped LiCoO 2 materials with high-density sphericity (LiCo 1-z Al z O 2 , remarked as "LCAO") shows a high initial specific capacity of 161 mAh g -1 at 0.1 C and excellent capacity retention of 99.5 % within 100 cycles at 1 C in the voltage range of 2.8 to 4.3 V. Our work provides valuable insights into the featured design of LiCoO 2 precursors and cathode materials from spent LiCoO 2 batteries, potentially guaranteeing the high-efficacy recycling and utilization of strategic resources., (© 2023 Wiley-VCH GmbH.)

Environmental enrichment has the potential to improve the welfare and post-release survival of hatchery fish stocked for conservation purposes. However, the effectiveness of environmental enrichment is partly dependent on the fish species, life stage, and specific enrichment structure used. To enhance the effectiveness of environmental enrichment, it is crucial to focus on characteristic differences in enrichment structures, such as type and level. This study investigated how differences in enrichment type and level affected physiological and behavioral aspects of the welfare of pre-release juvenile rock bream Oplegnathus fasciatus by evaluating growth performance, basal and stressed cortisol levels, antioxidant enzyme activities, and exploratory behaviors regarding anxiety and flexibility. Fish were reared for 4 weeks in different enrichment treatments: barren, low-level cover structure, high-level cover structure, low-level interference structure (LI), and high-level interference structure (HI). The results revealed that fish reared with the LI treatment showed less anxiety and greater flexibility with respect to exploratory behaviors, without oxidative damage being detected. Despite exhibiting less anxiety as well, fish reared in the HI treatment had oxidative damage, indicated by lower superoxide dismutase activity, compared to those in the barren treatment. In addition, none of these enrichment structures enhanced growth performance or mitigate chronic and acute stress responses. Overall, the low-level interference structure may be more favorable in promoting the behavioral welfare of the fish. Application of this type and level of enrichment may increase the survival of the hatchery fish after release, which is critical to stocking success., (© 2023 Fisheries Society of the British Isles.)

Probiotics are live microorganisms with immunomodulatory effects in a strain-specific and dose-dependent manner. Bifidobacterium animalis subsp. lactis IU100 is a new probiotic strain isolated from healthy adults. This study aimed to evaluate the effects of IU100 on cyclophosphamide (CTX)-induced immunosuppression in mice. The results showed that IU100 significantly ameliorated CTX-induced decreases in body weight and immune organ indices. The promoted delayed-type hypersensitivity, serum hemolysins and immunoglobulin (IgA, IgG and IgM) levels after IU100 treatment indicated its enhancing role in cellular and humoral immunity. In addition, oral administration of IU100 increased serum cytokine (IL-1β, IL-2, IL-4, IL-6, IFN-γ, TNF-α) levels dose-dependently, which are associated with CTX-induced shifts in the Th1/Th2 balance. The probiotic IU100 also modulated the composition of gut microbiota by reducing the Firmicutes/Bacteroidetes ratio; increasing beneficial Muribaculaceae and the Lachnospiraceae NK4A136 group; and inhibiting harmful Clostridium sensu stricto 1, Faecalibaculum and Staphylococcus at the genus level. The above genera were found to be correlated with serum cytokines and antibody levels. These findings suggest that IU100 effectively enhances the immune function of immunosuppressed mice, induced by CTX, by regulating gut microbiota.

For marine invertebrates, the disruption of organismal physiology and behavior by nanoplastics (NPs) has been extensively reported. Heat shock proteins (Hsps) are important for redundant protein breakdown, environmental changes, and intracellular protein transport. An exhaustive identification of Hsp70 genes and an experiment where different concentrations of NPs were stressed were performed to study how Hsp70 genes respond to NPs stress in Monodonta labio . Our results identified 15 members of Hsp70 within the genome of M. labio and provided insights into their responses to different concentrations of acute NP stress. Phylogenetic analyses revealed extensive amplification of the Hsp70 genes from the Hsc70 subfamily, with gene duplication events. As a result of NP stress, five of fifteen genes showed significant upregulation or downregulation. Three Hsp70 genes were highly expressed at an NP concentration of 0.1 mg/L, and no genes were downregulated. At 10 mg/L, they showed significant upregulation of two genes and significant downregulation of two genes. At 1 mg/L treatment, three genes were significantly downregulated, and no genes were significantly upregulated. Moreover, a purifying selection was revealed using a selection test conducted on duplicate gene pairs, indicating functional redundancy. This work is the first thorough examination of the Hsp70s in Archaeogastropoda. The findings improve knowledge of Hsp70s in molluscan adaptation to NP stress and intertidal living and offer essential data for the biological study of M. labio .

The Gram-negative marine bacterium GXY010 T , which has been isolated from the surface seawater of the western Pacific Ocean, is aerobic, non-motile and non-flagellated. Strain GXY010 T exhibits growth across a temperature range of 10-42 °C (optimal at 37 °C), pH tolerance from 7.0 to 11.0 (optimal at 7.5) and a NaCl concentration ranging from 1.0 to 15.0% ( w / v , optimal at 5.0%). Ubiquinone-8 (Q-8) was the predominant isoprenoid quinone in strain GXY010 T . The dominant fatty acids (>10%) of strain GXY010 T were iso-C 15:0 (14.65%), summed feature 9 (iso-C 17:1 ω 9 c and/or 10-methyl C 16:0 ) (12.41%), iso-C 17:0 (10.85%) and summed feature 3 (C 16:1 ω 7 c and/or C 16:1 ω 6 c ) (10.41%). Phosphatidylethanolamine (PE), phosphatidylglycerol (PG), diphosphatidylglycerol (DPG), unidentifiable glycolipid (GL) and four non-identifiable aminolipids (AL1-AL4) were the predominant polar lipids of strain GXY010 T . The genomic DNA G+C content was identified as a result of 48.0% for strain GXY010 T . The strain GXY010 T genome consisted of 2,766,857 bp, with 2664 Open Reading Frames (ORFs), including 2586 Coding sequences (CDSs) and 78 RNAs. Strain GXY010 T showed Average Nucleotide Identity (ANI) values of 73.4% and 70.6% and DNA-DNA hybridization (DDH) values of 19.2% and 14.5% with reference species Pseudidiomarina tainanensis MCCC 1A02633 T (=PIN1 T ) and Pseudidiomarina taiwanensis MCCC 1A00163 T (=PIT1 T ). From the results of the polyphasic analysis, a newly named species, Pseudidiomarina fusca sp. nov. within the genus Pseudidiomarina , was proposed. The type strain of Pseudidiomarina fusca is GXY010 T (=JCM 35760 T = MCCC M28199 T = KCTC 92693 T ).

Objective: The efficacy of sirolimus in treating severe or refractory systemic lupus erythematosus (SLE) has been confirmed by small-scale clinical trials. However, few studies focused on mild or moderate SLE. Therefore, in this study we elucidated clinical efficacy of add-on sirolimus in patients with mild or moderate SLE., Methods: Data of 17 consecutive patients with SLE were retrospectively collected. SLE Disease Activity Index-2000 (SLEDAI-2K), clinical manifestation, laboratory data and peripheral T lymphocyte subsets with cytokines were collected before and 6 months after sirolimus add-on treatment. T cell subsets were detected by flow cytometry and cytokines were determined by multiplex bead-based flow fluorescent immunoassay simultaneously. Twenty healthy controls matched with age and sex were also included in our study., Results: (1) The numbers of peripheral blood lymphocytes, T cells, T helper (Th) cells, regulatory T (Treg) cells, Th1 cells, Th2 cells and Treg/Th17 ratios in patients with SLE were significantly lower, while the numbers of Th17 cells were evidently higher than those of healthy control (p<0.05). (2) After 6 months of sirolimus add-on treatment, urinary protein, pancytopenia, immunological indicators and SLEDAI-2K in patients with SLE were distinctively improved compared with those before sirolimus treatment (p<0.05). (3) The numbers of peripheral blood lymphocytes, T cells, Th cells, Treg cells, Th2 cells and the ratios of Treg/Th17 in patients with SLE after treatment were clearly higher than those before (p<0.05). (4) The levels of plasma interleukin (IL)-5, IL-6 and IL-10 in patients with SLE decreased notably, conversely the IL-4 levels increased remarkably compared with pretreatment (p<0.05)., Conclusions: (1) Patients with SLE presented imbalanced T cell subsets, especially the decreased ratio of Treg/Th17. (2) Sirolimus add-on treatment ameliorated clinical involvement, serological abnormalities and disease activity without adverse reactions in patients with SLE. (3) The multi-target therapy facilitates the enhanced numbers of Treg cells, Treg/Th17 imbalance and anti-inflammatory cytokines, simultaneously, reducing inflammatory cytokines., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Study Objectives: To evaluate the efficacy and safety of Dimdazenil, a novel partial positive allosteric modulator for GABAA receptor in adults with insomnia disorder., Methods: This was a 2-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III study of Dimdazenil. The primary efficacy outcome was total sleep time (TST) analyzed by polysomnography (PSG) on day 13/14. Latency to persistent sleep (LPS), sleep efficiency (SE), and wake after sleep onset (WASO) were analyzed in the same way by polysomnography (PSG). The other secondary outcomes including the average subjective sleep latency (sSL), subjective TST (sTST), subjective SE (sSE), subjective WASO (sWASO), and subjective number of awakenings (sNAW) were analyzed from sleep diary data, and the insomnia severity index (ISI) was also assessed. Treatment-emergent adverse events (TEAEs) were monitored throughout the study., Results: A total of 546 participants with insomnia (age ≥18 years) were randomized (2:1), received treatment with an oral dose of Dimdazenil (2.5 mg) or placebo, and analyzed. Compared to baseline and placebo, Dimdazenil demonstrated significant improvements in PSG measures, increased TST (71.09, 31.68 minutes, respectively; both p < 0.001), increased SE (13.26%, 5.55%, respectively; both < 0.001), reduced WASO (49.67, 20.16 minutes, respectively; both p < 0.001), and reduced LPS (21.65 minutes, p < 0.001; 6.46 minutes, p = 0.023). Compared to placebo, Dimdazenil also improved key self-reported measures of sTST (18.33 minutes, p < 0.001), sWASO (14.60 minutes, p < 0.001), sSL (4.23 minutes, p < 0.001), sSE (2.97%, p < 0.001), and sNAW (0.29, p < 0.001). Participants treated with Dimdazenil reported a significant improvement in ISI. Dimdazenil was well tolerated. The majority of TEAEs were mild or moderate. There were no clinically relevant treatment-related serious AEs and no deaths., Conclusions: Dimdazenil of 2.5 mg provided significant benefit on sleep maintenance and sleep onset in individuals with insomnia disorder versus placebo, with a favorable safety profile and was well tolerated., Clinical Trial Information: A multicenter, randomized, double-blind phase III clinical study evaluating the efficacy and safety of EVT201 capsules compared to placebo in patients with insomnia disorders (http://www.chinadrugtrials.org), with the number of CTR20201068., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society.)

Study Objectives: To evaluate the efficacy and safety of Dimdazenil, a positive allosteric modulator with selectivity for α1, α5 subunit-containing GABAA receptors, on sleep variables in patients with insomnia disorder., Methods: In this randomized, double-blind, placebo-controlled trial, adults (18-65 years) with insomnia disorder were randomized (1:1:1:1 to receive daily oral placebo, Dimdazenil (1.5, 2.5, or 5 mg) for 14 days. The primary efficacy outcome was the total sleep time (TST) on day 1/2 and day 13/14, measured by polysomnography. The secondary outcome measures included (1) latency to persistent sleep (LPS), sleep efficiency (SE), wake after sleep onset (WASO) and number of awakenings (NAW) on days 1/2 and day 13/14, and (2) the average subjective sleep latency (sSL), total sleep time (sTST), wake after sleep onset (sWASO) and number of awakenings (sNAW) recorded in sleep diary and sleep questionnaire, and the evaluation of insomnia severity index. Rebound insomnia, withdrawal, and treatment-emergent adverse events were also assessed., Results: Of 569 patients screened, 288 (76.4% female) were randomized and received one dose. For the primary outcomes, TST was significantly improved in the Dimdazenil 1.5, 2.5, and 5 mg group compared with the placebo group at day 1/2, and significantly improved in the Dimdazenil 2.5 and 5 mg groups compared with the placebo group at day 13/14. The Least Squares Means (standard errors) and 95% Confidence Intervals for the three active doses compared to placebo are 25.5 (8.31), (9.16, 41.89) for the 1.5 mg dose; 17.4 (8.19), (1.29, 33.55) for the 2.5 mg dose; 22.8 (8.15), (6.72, 38.80) for the 5 mg dose on day 1/2. Corresponding data on day 13/14 are 7.6 (8.07), (-8.24, 23.53) and 19.3 (8.06), (3.43, 35.17) and 18.2 (7.95), (2.49, 33.80). LPS was significantly reduced in the Dimdazenil 5 mg group compared with the placebo group on day 1/2. SE was significantly improved in the Dimdazenil 1.5 and 5 mg group compared with the placebo group at day 1/2. In the subjective sleep parameters, sSL on average was significantly lower in the Dimdazenil 1.5, 2.5, and 5 mg groups compared with the placebo group. sTST on average was significantly higher in the Dimdazenil 1.5, 2.5, and 5 mg groups compared with the placebo group. The most common TEAEs were dizziness, vertigo, and weakness with no clinically relevant treatment-related serious adverse events., Conclusions: Dimdazenil of 1.5, 2.5, and 5 mg improved certain objective and subjective sleep outcomes in people with insomnia disorder, with a favorable safety profile. These findings suggested that Dimdazenil may represent a promising new treatment for insomnia disorder, a prevalent condition with limited effective and safe treatments available., Clinical Trial Information: A multicenter, randomized, double-blind, multidose, placebo parallel controlled phase II clinical study of EVT201 in the treatment of insomnia disorders (http://www.chinadrugtrials.org), with the number of CTR20150664., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society.)

Introduction: Women with perinatal anxiety have reduced coping capacity during labor, which affects labor progress and increases the likelihood of a cesarean section. Several non-pharmacological interventions for anxiety during childbirth are available. This study used the "lite touch" method, a non-pharmacological intervention based on physiological responses and obstetric clinical experience in women. We aimed to evaluate whether lite touch could relieve perinatal anxiety and investigate the effect of light skin stroking on the maternal hormones, catecholamine, and cortisol., Methods: This randomized clinical trial involved women with low-risk singleton pregnancies at full term or near term. Eligible pregnant women who were latent and did not undergo epidural anesthesia were randomized into two groups. Participants in the intervention group underwent routine prenatal care, including lite touch, whereas the control group underwent routine prenatal care alone. Demographic data were collected through a questionnaire. Labor anxiety was assessed using the State Anxiety Inventory, and saliva was collected before and after the intervention. Changes in saliva cortisol and catecholamine levels were analyzed using a double-antibody sandwich enzyme-linked immunosorbent assay., Results: In total, 83 participants were included, with 43 and 40 in the intervention and control groups, respectively. In the intervention group, pre-intervention anxiety scores were significantly lower ( p  < 0.01) than post-intervention anxiety scores, whereas the control group showed no difference in anxiety scores before and after intervention ( p  > 0.05). Cortisol and catecholamine levels in saliva were significantly lower in the intervention group than in the control group after the intervention ( p  < 0.01)., Discussion: Lite touch can reduce the latent anxiety state of low-risk pregnant women, thereby maintaining in vivo stability and facilitating labor., Clinical Trial Registration: https://www.chictr.org.cn/aboutEN.html, ChiCTR2300070905, Retrospectively Registered Date: April 26, 2023., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Wang, Ko, Niu, Huang, Luo, Wang, He and Li.)

Flow-induced random vibration propagates throughout a plate-like structure and thus contains information about the structural properties and states. Previous research has shown that the group velocity under various frequencies can be estimated by the cross-correlation between two measurement points, in which the prominent peak signifies the travel time of the random guided wave. However, it is found that the performance of this method depends on the sensor placement and the plate size; in some cases, the cross-correlation is contaminated such that the extraction of dispersion curve is problematic. This is because the wave package in the cross-correlation corresponding to the direct propagation between the two sensors overlaps with the coda wave packages associated with complex boundary reflections. This hypothesis is justified by a passive experiment on an ellipse-shaped plate: in the cross-correlation between the foci of the ellipse, the imprints of the direct propagation and various orders of boundary reflections can be clearly separated and precisely predicted by the ray method. Based on these findings, a sensor placement criterion is proposed, by which a robust passive reconstruction of dispersion curve using flow-induced random vibration is guaranteed., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xun WANG reports financial support was provided by National Natural Science Foundation of China. Xun WANG reports financial support was provided by Beihang University National Key Laboratory of Science and Technology on Reliability and Environmental Engineering. Xun WANG reports a relationship with Beihang University that includes: employment., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Inconsistent findings exist regarding the relationship between heme iron intake and type 2 diabetes (T2D) among Western and Eastern populations. Easterners tend to consume a plant-based diet which is abundant in antioxidant minerals. To examine the hypothesis that antioxidant mineral may modify the relationship between iron and T2D, we performed a case-control study by measuring the serum mineral levels in 2198 Chinese subjects. A total of 2113 T2D patients and 2458 controls were invited; 502 T2D patients and 1696 controls were finally analyzed. In the total population, high serum iron showed a positive association with T2D odds (odds ratio [OR] = 1.27 [1.04, 1.55]); high magnesium (OR = 0.18 [0.14, 0.22]), copper (OR = 0.27 [0.21, 0.33]), zinc (OR = 0.37 [0.30, 0.46]), chromium (OR = 0.61 [0.50, 0.74]), or selenium concentrations (OR = 0.39 [0.31, 0.48]) were inversely associated with T2D odds. In contrast, in individuals with higher magnesium (>2673.2 µg/dL), zinc (>136.7 µg/dL), copper (>132.1 µg/dL), chromium (>14.0 µg/dL), or selenium concentrations (>16.8 µg/dL), serum iron displayed no association with T2D ( p > 0.05). Serum copper and magnesium were significant modifiers of the association between iron and T2D in individuals with different physiological status ( p < 0.05). Our findings support the idea that consuming a diet rich in antioxidant minerals is an effective approach for preventing T2D.

A total of 66 sets of pullout specimens were prepared to investigate the bonding properties of basalt fiber-reinforced polymer reinforcement (hereinafter referred to as BFRP) with seawater sand concrete (hereinafter referred to as SSC). The volume dosages of mono-doped glass fibers and mono-doped polypropylene fibers were 0.1%, 0.2%, and 0.3%; the total volume dosage was set to be constant at 0.3%; and the doping ratios of the hybrid fibers were 1:2, 1:1, and 2:1. The effect on the bonding performance of BFRP reinforcement with SSC was studied on the condition of the diameter D of the BFRP reinforcement being 12 mm; the bond length of SSC being 3D, 5D, and 7D; and the surface characteristics of the reinforcement being sandblasted and threaded. The research showed that due to internal cracks in the matrix, salt crystals in the pores, chloride salts with high brittleness and expansion, as well as sulfate corrosion products such as "Frederick salts" in SSC, the concrete became brittle, resulting in more brittle splitting failures during the pullout test. Doped fibers can increase the ductility effect of concrete, but the bonding effect between the threaded fiber reinforcement and the SSC was not as good as that of the sandblasting group. When the bond length was 5D, the bonding effect between the BFRP reinforcement and SSC was the best, and the bonding performance of the experimental group with doped fibers was better than that of the threaded group. Finally, by combining the ascending segment of the Malvar model with the descending segment of the improved BPE model, a constitutive relationship model suitable for the bond-slip curve between BFRP reinforcement and SSC was fitted, which laid a theoretical foundation for future research on SSC.

Current treatment for functional dyspepsia (FD) has limited and unsustainable efficacy. Probiotics have the sustainable potential to alleviate FD. This randomized controlled clinical trial (Chinese Clinical Trial Registry, ChiCTR2000041430) assigned 200 FD patients to receive placebo, positive-drug (rabeprazole), or Bifidobacterium animalis subsp. lactis BL-99 (BL-99; low, high doses) for 8-week. The primary outcome was the clinical response rate (CRR) of FD score after 8-week treatment. The secondary outcomes were CRR of FD score at other periods, and PDS, EPS, serum indicators, fecal microbiota and metabolites. The CRR in FD score for the BL-99&#95;high group [45 (90.0%)] was significantly higher than that for placebo [29 (58.0%), p = 0.001], BL-99&#95;low [37 (74.0%), p = 0.044] and positive&#95;control [35 (70.0%), p = 0.017] groups after 8-week treatment. This effect was sustained until 2-week after treatment but disappeared 8-week after treatment. Further metagenomic and metabolomics revealed that BL-99 promoted the accumulation of SCFA-producing microbiota and the increase of SCFA levels in stool and serum, which may account for the increase of serum gastrin level. This study supports the potential use of BL-99 for the treatment of FD., (© 2024. The Author(s).)

Background: The association between TCF7L2 and CAPN10 gene polymorphisms and gestational diabetes mellitus (GDM) has been explored in diverse populations across different geographical regions. Yet, most of these studies have been confined to a limited number of loci, resulting in inconsistent findings. In this study, we conducted a comprehensive review of published literature to identify studies examining the relationship between TCF7L2 and CAPN10 gene polymorphisms and the incidence of GDM in various populations. We specifically focused on five loci that were extensively reported in a large number of publications and performed a meta-analysis., Methods: We prioritized the selection of SNPs with well-documented correlations established in existing literature on GDM. We searched eight Chinese and English databases: Cochrane, Elton B. Stephens. Company (EBSCO), Embase, Scopus, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and China Science and Technology Journal Database and retrieved all relevant articles published between the inception of the database and July 2022. The Newcastle Ottawa Scale (NOS) was used to evaluate the selected articles, and the odds ratio (OR) was used as the combined effect size index to determine the association between genotypes, alleles, and GDM using different genetic models. Heterogeneity between the studies was quantified and the I 2 value calculated. Due to large heterogeneities between different ethnic groups, subgroup analysis was used to explore the correlation between genetic polymorphisms and the incidence of GDM in the different populations. The stability of the results was assessed using sensitivity analysis. Begg's and Egger's tests were used to assess publication bias., Results: A total of 39 articles reporting data on 8,795 cases and 16,290 controls were included in the analysis. The frequency of the rs7901695 genotype was statistically significant between cases and controls in the European population (OR = 0.72, 95% CI: 0.65-0.86) and the American population (OR = 0.61, 95% CI: 0.48-0.77). The frequencies of rs12255372, rs7901695, rs290487, and rs2975760 alleles were also considerably different between the cases and controls in the populations analyzed., Conclusions: rs7903146, rs12255372, rs7901695, rs290487, and rs2975760 were associated with the incidence of GDM in different populations., (© 2024. The Author(s).)

Background: The demand for mammaplasty has increased in recent years, and infection remains one of the common and serious post-operative complications. In this study, we analyzed the pathogen distribution and antibiotic susceptibility of breast plastic surgery infections, and compared the differences in pathogenic species between surgical procedures., Methods: The number of each species was counted in the microbial samples of breast plastic surgery infections in Plastic Surgery Hospital of Chinese Academy of Medical Sciences from January 2011 to December 2021. The in vitro antibiotic sensitivity testing data were analyzed using WHONET 5.6 software. The surgical techniques, the period of infection, and other details were gathered in accordance with the clinical data., Results: There were a total of 42 cases included, and 43 different types of pathogenic bacteria, mostly gram-positive bacteria, were found. CoNS (13/43) and Staphylococcus aureus (22/43) made up the majority. The most prevalent of the five Gram-negative bacteria was Pseudomonas aeruginosa. Results of drug sensitivity tests indicate that S. aureus is highly sensitive to vancomycin, cotrimoxazole, and linezolid, whereas CoNS is highly sensitive to vancomycin, linezolid, and chloramphenicol. Both of these bacteria show high resistance to erythromycin and penicillin. Breast augmentation, breast reconstruction, and breast reduction surgery were the most frequently associated breast surgery procedures in this study with infections, with the highest number of infections occurring following breast augmentation with fat grafting, breast reduction surgery, and breast reconstruction with autologous tissue. Various breast plastic surgery procedures have different common pathogens of infection, but the most prevalent are CoNS and S. aureus. Additionally, the majority of the infections in this study were in the early stages., Conclusions: Gram-positive bacteria were the predominant cause of breast plastic surgery infections, and the types of infection strains, the period of infection onset, and the antibiotic susceptibility of prevalent strains varied between breast plastic procedures., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

To combat microbial pathogens, plants have evolved specific immune responses that can be divided into three essential steps: microbial recognition by immune receptors, signal transduction within plant cells, and immune execution directly suppressing pathogens. During the past three decades, many plant immune receptors and signaling components and their mode of action have been revealed, markedly advancing our understanding of the first two steps. Activation of immune signaling results in physical and chemical actions that actually stop pathogen infection. Nevertheless, this third step of plant immunity is under explored. In addition to immune execution by plants, recent evidence suggests that the plant microbiota, which is considered an additional layer of the plant immune system, also plays a critical role in direct pathogen suppression. In this review, we summarize the current understanding of how plant immunity as well as microbiota control pathogen growth and behavior and highlight outstanding questions that need to be answered., (© 2023. The Author(s).)

Background: JX11502MA is a potent partial agonist of dopamine D2 and D3 receptors, with a preferential binding profile for D3 receptors in vitro, potentially for treating schizophrenia., Methods: A first-in-human, randomized, double-blind, placebo-controlled, single ascending dose clinical trial was designed. The subjects were randomly assigned to receive JX11502MA and placebo capsules with seven ascending dose groups: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 6 mg, and 8 mg. The PK profiles of JX11502MA and its metabolites were evaluated, along with a safety and tolerability assessment., Results: Considering the safety of participants, the dose escalation was halted at 3 mg. Following single-dose administration, JX11502MA exhibited rapid absorption with a median T max ranging from 1 to 1.75 h. The terminal half-life of JX11502MA ranged from 73.62 to 276.85 h. The most common treatment-emergent adverse events (TEAEs) for subjects receiving JX11502MA were somnolence (56.3%), dizziness (18.8%), nausea (21.9%), vomiting (18.8%), and hiccups (18.8%)., Conclusions: JX11502MA was generally well tolerated at a single dose of 0.25 to 3 mg. The PK profiles and safety characteristics in this study indicated that JX11502MA has the potential to be a favorable treatment option for patients with schizophrenia., Trial Registration: https://clinicaltrials.gov (identifier: NCT05233657).