Efficacy of Lacticaseibacillus paracasei fermented milk on a model of constipation induced by loperamide hydrochloride in BALB/c mice.

Currently, most studies focus on the functions of probiotic-fermented milk, whereas there are relatively few studies on the function of postbiotic-fermented milk in relieving constipation. In this study, we aimed to assess the modulation of constipation symptoms and its mechanism of action by different concentrations of Lacticaseibacillus paracasei-fermented milk as a postbiotic in a loperamide hydrochloride-induced constipation model in BALB/c mice. By comparing the relevant indexes, colon histological analysis, gene expression level, and intestinal flora structure in the constipation model of mice, we found that high and ultra-high doses of fermented milk can effectively relieve constipation. Fermented milk effectively reduced defecation time, increased the rate of small intestinal propulsion in constipated mice, and alleviated colonic inflammation, safeguarding the normal function of the intestinal tract. In addition, it can regulate the intestinal flora, downregulate the abundance of Proteobacteria, upregulate the abundance of species of Firmicutes and Actinobacteriota, and improve the overall abundance level of intestinal flora in mice.

Multivalent Cu sites synergistically adjust carbonaceous intermediates adsorption for electrocatalytic ethanol production.

Copper (Cu)-based catalysts show promise for electrocatalytic CO2 reduction (CO2RR) to multi-carbon alcohols, but thermodynamic constraints lead to competitive hydrocarbon (e.g., ethylene) production. Achieving selective ethanol production with high Faradaic efficiency (FE) and current density is still challenging. Here we show a multivalent Cu-based catalyst, Cu-2,3,7,8-tetraaminophenazine-1,4,6,9-tetraone (Cu-TAPT) with Cu2+ and Cu+ atomic ratio of about 1:2 for CO2RR. Cu-TAPT exhibits an ethanol FE of 54.3 ± 3% at an industrial-scale current density of 429 mA cm-2, with the ethanol-to-ethylene ratio reaching 3.14:1. Experimental and theoretical calculations collectively unveil that the catalyst is stable during CO2RR, resulting from suitable coordination of the Cu2+ and Cu+ with the functional groups in TAPT. Additionally, mechanism studies show that the increased ethanol selectivity originates from synergy of multivalent Cu sites, which can promote asymmetric C-C coupling and adjust the adsorption strength of different carbonaceous intermediates, favoring hydroxy-containing C2 intermediate (*HCCHOH) formation and formation of ethanol.

Durable response to pembrolizumab in hepatic metastasis from colonic carcinoma with Lynch syndrome: a case report.

Pembrolizumab and other immunotherapies have become central in treating metastatic colon cancer, particularly effective in patients with mismatch repair deficiencies. We report a case involving a man who initially underwent radical surgery for sigmoid colon cancer on April 27, 2011, followed by hepatic tumor resection on September 21, 2017. Post-surgery, he received eight cycles of adjuvant chemotherapy with the CAPEOX regimen and was regularly monitored through CT and MRI scans. On August 24, 2022, liver metastases were detected, and he was diagnosed with Lynch syndrome (LS) due to germline mutation in the MSH2 and EPCAM genes. He commenced treatment with 200mg of pembrolizumab intravenously every three weeks on September 2, 2022, and demonstrated a sustained response. However, after 17 cycles, he developed a treatment related adverse event (TRAE) of pancreatic endocrine dysfunction, leading to type 1 diabetes, managed with subcutaneous insulin injections. After 30 cycles of treatment, no evidence of disease was observed. This case underscores the significant clinical benefits of first-line pembrolizumab in managing hepatic metastasis in colonic carcinoma associated with LS, despite the occurrence of TRAEs. It raises critical questions regarding the optimal duration of immunotherapy following a complete or partial response and whether treatment should be discontinued upon the emergency of TRAEs. Continued research and forthcoming clinical trials with checkpoint inhibitors are expected to refine treatment protocols for LS-associated carcinoma.

hUC-MSC Combined with DHEA Alleviates Ovarian Senescence in Naturally Aging Mice through Enhancing Antioxidant Capacity and Inhibiting Inflammatory Response.

The ovary is an important organ for women to maintain reproductive and endocrine functions. Ovarian aging can lead to female reproductive aging, which is a key factor causing rapid aging of the female body. Umbilical cord-derived MSCs (UC-MSCs) play a therapeutic role in various degenerative diseases. Dehydroepiandrosterone (DHEA) is widely used in the treatment of reversing oocyte quality. However, it is unclear whether UC-MSCs combined with DHEA supplementation can improve ovarian senescence in naturally aging mice. To address this question, we studied the influence of the combination of human UC-MSCs (hUC-MSCs) and DHEA on ovarian morphology and function in naturally aging mice. The results showed a significant augmentation in the number of primary follicles, as well as a significant upregulation of estradiol (E2), follicle-stimulating hormone (FSH), and anti-Mullerian hormone (AMH) hormone levels, and a significant increase in survival rate in naturally aging mice treated by hUC-MSCs and DHEA. Moreover, the combination of hUC-MSCs and DHEA significantly reduced the reactive oxygen species (ROS) level and downregulated the expression levels of proinflammatory factors IL-6, IL-18, and TNF-α. Furthermore, the PI3K/AKT/mTOR pathway was inhibited. Conclusively, the combination therapy of hUC-MSC + DHEA contributed to restore ovarian function in aging mice and extend their lifespan by restoring hormone levels and inhibiting inflammatory factors.

Relationship between serum iron, zinc, calcium, and HIF-1a-comparative analysis of 2 regions and 4 ethnic groups in China.

Background: Altitude illness has serious effects on individuals who are not adequately acclimatized to high-altitude areas and may even lead to death. However, the individualized mechanisms of onset and preventive measures are not fully elucidated at present, especially the relationship between altitude illness and elements, which requires further in-depth research. Methods: Fresh serum samples were collected from individuals who underwent health examinations at the two hospitals in Xining and Sanya between November 2021 and December 2021. The blood zinc (Zn), iron (Fe), and calcium (Ca) concentrations, as well as hypoxia-inducible factor 1-alpha (HIF-1α) concentrations, were measured. This study conducted effective sample size estimation, repeated experiments, and used GraphPad Prism 9.0 and IBM SPSS version 19.0 software for comparative analysis of differences in the expression of elements and HIF-1α among different ethnic groups, altitudes, and concentration groups. Linear regression and multiple linear regression were employed to explore the relationships among elements and their correlation with HIF-1α. Results: This study included a total of 400 participants. The results from the repeated measurements indicated that the consistency of the laboratory test results was satisfactory. In terms of altitude differences, except for Fe (p = 0.767), which did not show significant variance between low and high altitude regions, Zn, Ca, and HIF-1α elements all exhibited notable differences between these areas (p < 0.0001, p = 0.004, and p < 0.0001). When grouping by the concentrations of elements and HIF-1α, the results revealed significant variations in the distribution of zinc among different levels of iron and HIF-1α (p < 0.05). The outcomes of the linear regression analysis demonstrated that calcium and zinc, iron and HIF-1α, calcium and HIF-1α, and zinc and HIF-1α displayed substantial overall explanatory power across different subgroups (p < 0.05). Finally, the results of the multiple linear regression analysis indicated that within the high-altitude population, the Li ethnic group in Sanya, and the Han ethnic group in Sanya, the multiple linear regression model with HIF-1αas the dependent variable and elements as the independent variables exhibited noteworthy overall explanatory power (p < 0.05). Conclusion: The levels of typical elements and HIF-1α in the blood differ among various altitudes and ethnic groups, and these distinctions may be linked to the occurrence and progression of high-altitude illness.

Associations of ACE I/D and AGTR1 rs5182 polymorphisms with diabetes and their effects on lipids in an elderly Chinese population.

BACKGROUND: Diabetes mellitus is generally accompanied by dyslipidaemia, but inconsistent relationships between lipid profiles and diabetes are noted. Moreover, genetic variations in insertion/deletion (I/D) polymorphisms at angiotensin-converting enzyme gene (ACE) and T/C polymorphisms in the angiotensin type 1 receptor gene (AGTR1) are related to diabetes and lipid levels, but the associations are controversial. Thus, the current research aimed to explore the effects of ACE I/D, AGTR1 rs5182 and diabetes mellitus on serum lipid profiles in 385 Chinese participants with an average age of 75.01 years. METHODS: The ACE I/D variant was identified using the polymerase chain reaction (PCR) method, whereas the AGTR1 rs5182 polymorphism was identified using the PCR-based restriction fragment length polymorphism (PCR-RFLP) method and verified with DNA sequencing. Total cholesterol (TC), triglyceride (TG), apolipoprotein A (ApoA), apolipoprotein B (ApoB), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were measured using routine methods, and the lipid ratios were calculated. RESULTS: ACE I/D, but not AGTR1 rs5182, was a predictor of TG/HDL-C for the whole study population. Both ACE I/D and AGTR1 rs5182 were predictors of HDL-C and LDL-C levels in females but not in males. Moreover, in females, diabetes mellitus and ACE I/D were identified as predictors of TG and TG/HDL-C, whereas AGTR1 rs5182 and diabetes mellitus were predictors of TG/HDL-C. Moreover, diabetes mellitus and the combination of ACE I/D and AGTR1 rs5182 variations were predictors of TG and TG/HDL-C exclusively in females. CONCLUSIONS: The results demonstrated the potential for gender-dependent interactions of ACE I/D, AGTR1 rs5182, and diabetes on lipid profiles. These findings may serve as an additional explanation for the inconsistent changes of blood lipids in individuals with diabetes mellitus, thereby offering a novel perspective for the clinical management of blood lipid levels in diabetic patients.

Spur development and evolution: An update.

Floral spurs, widely recognized as a classic example of key morphological and functional innovation and thought to have promoted the origin and adaptive evolution of many flowering plant lineages, have attracted the attention of researchers for centuries. Despite this, the mechanisms underlying the development and evolution of these structures remain poorly understood. Recent studies have discovered the phytohormones and transcription factor genes that play key roles in regulating patterns of cell division and cell expansion during spur morphogenesis. Spur morphogenesis was also found to be tightly linked with the programs specifying floral zygomorphy, floral organ identity determination, and nectary development. Independent origins and losses of spurs in different flowering plant lineages, therefore, may be attributed to changes in the spur program and/or its upstream ones.

Suicidal ideation in adolescents with adiponectin receptor 2 rs12342 polymorphism affected by Wenchuan earthquake.

PURPOSE: The present study was to investigate prevalence of suicidal ideation and its associations with biological and environmental factors in adolescents with different genotypes of rs12342 at adiponectin receptor 2 gene (ADIPOR2). METHODS: Suicidal ideation, biological and environmental factors were evaluated by questionnaires in 669 high school students after Wenchuan earthquake in China. ADIPOR2 rs12342 was genotyped by polymerase chain reaction-restriction fragment length polymorphism and verified by DNA sequencing. RESULTS: Female adolescents had higher prevalence of suicidal ideation than male students in AG heterozygote and GG homozygote, but not AA homozygote. Prevalence of suicidal ideation was different in male, but not female, subjects with different genotypes. Genotype and allele frequencies were significantly different between male students with and without suicidal ideation, but not the female counterparts. Family history of mental disorders, extent of damage to property, carbohydrate intake and protein intake were associated with suicidal ideation in female subjects, while ADIPOR2 rs12342, father's educational level and previous trauma experience were associated with suicidal ideation in male subjects. CONCLUSION: ADIPOR2 rs12342 is associated with and has potential to interact with environmental factors on suicidal ideation in a gender-dependent manner in youth. These findings pave a novel way and perspective for precision inferences of suicidal ideation in subjects with different genetic backgrounds. ADIPOR2 rs12342 needs to be considered when intervening suicidal ideation, especially in adolescents.

Realization of monolayer ZrTe5 topological insulators with wide band gaps.

Two-dimensional topological insulators hosting the quantum spin Hall effect have application potential in dissipationless electronics. To observe the quantum spin Hall effect at elevated temperatures, a wide band gap is indispensable to efficiently suppress bulk conduction. Yet, most candidate materials exhibit narrow or even negative band gaps. Here, via elegant control of van der Waals epitaxy, we have successfully grown monolayer ZrTe5 on a bilayer graphene/SiC substrate. The epitaxial ZrTe5 monolayer crystalizes in two allotrope isomers with different intralayer alignments of ZrTe3 prisms. Our scanning tunneling microscopy/spectroscopy characterization unveils an intrinsic full band gap as large as 254 meV and one-dimensional edge states localized along the periphery of the ZrTe5 monolayer. First-principles calculations further confirm that the large band gap originates from strong spin-orbit coupling, and the edge states are topologically nontrivial. These findings thus provide a highly desirable material platform for the exploration of the high-temperature quantum spin Hall effect.

An 'activator-repressor' loop controls the anthocyanin biosynthesis in red-skinned pear.

The color of red-skinned pear (Pyrus spp.) is primarily attributed to accumulation of anthocyanins, which provide nutritional benefits for human health and are closely associated with the commercial value of fruits. Here, we reported the functional characterization of a R2R3-MYB repressor PyMYB107, which forms an 'activator-repressor' loop to control anthocyanin accumulation in the red-skinned pear. PyMYB107 overexpression inhibited anthocyanin biosynthesis in both pear calli and fruits, while virus-induced gene silencing of PyMYB107 increased anthocyanin accumulation in pear fruits. Furthermore, ectopic expression of PyMYB107 decreased anthocyanin accumulation in tomato, strawberry and tobacco. PyMYB107 can competitively bind to PybHLH3 with PyMYB10/MYB114, thereby suppressing the transcriptional activation of key anthocyanin biosynthesis genes, PyANS and PyUFGT. Site-directed mutagenesis showed that mutations within the R3 domain and EAR motif of PyMYB107 eliminated its repressive activity. Additionally, PyMYB107 exhibited a comparable expression pattern to PyMYB10/MYB114 and was transcriptionally activated by them. Our finding advanced comprehension of the repression mechanism underlying anthocyanin accumulation, providing valuable molecular insights into improving quality of pear fruits.

Human Umbilical Cord Mesenchymal Stem Cells Combined with Dehydroepiandrosterone Inhibits Inflammation-Induced Uterine Aging in Mice.

With the postponement of the reproductive age of women, the difficulty of embryo implantation caused by uterine aging has become a key factor restricting fertility. However, there are few studies on protective interventions for naturally aging uteri. Although many factors cause uterine aging, such as oxidative stress (OS), inflammation, and fibrosis, their impact on uterine function manifests as reduced endometrial receptivity. This study aimed to use a combination of human umbilical cord mesenchymal stem cells (hUC-MSCs) and dehydroepiandrosterone (DHEA) to delay uterine aging. The results showed that the combined treatment of hUC-MSCs + DHEA increased the number of uterine glandular bodies and the thickness of the endometrium while inhibiting the senescence of endometrial epithelial cells. This combined treatment alleviates the expression of OS (reactive oxygen species, superoxide dismutase, and GSH-PX) and proinflammatory factors (interleukin [IL]-1, IL6, IL-18, and tumor necrosis factor-α) in the uterus, delaying the aging process. The combined treatment of hUC-MSCs + DHEA alleviated the abnormal hormone response of the endometrium, inhibited excessive accumulation and fibrosis of uterine collagen, and upregulated uterine estrogen and progesterone receptors through the PI3K/AKT/mTOR pathway. This study suggests that uterine aging can be delayed through hUC-MSCs + DHEA combination therapy, providing a new treatment method for uterine aging.

KAT7 serves as an oncogenic gene and regulates CCL3 expression via STAT1 signaling in osteosarcoma.

Osteosarcoma, considered as the primary cause of malignant bone tumors in children, necessitates novel therapeutic strategies to enhance overall survival rates. KAT7, a histone acetyltransferase, exerts pivotal functions in gene transcription and immune modulation. In light of this, our study identified a significant upregulation of KAT7 in the mRNA and protein levels in human osteosarcoma, boosting cell proliferation in vivo and in vitro. In addition, KAT7-mediated H3K14ac activation induced MMP14 transcription, leading to increased expression and facilitation of osteosarcoma cell metastasis. Subsequent bioinformatics analyses highlighted a correlation between KAT7 and adaptive immune responses, indicating CCL3 as a downstream target of KAT7. Mechanistically, STAT1 was found to transcriptionally upregulate CCL3 expression. Furthermore, overexpression of KAT7 suppressed CCL3 secretions, whereas knockdown of KAT7 enhanced its release. Overall, these findings underscore the oncogenic role of KAT7 in regulating immune responses for osteosarcoma treatment.

Xiaoqinglong decoction mitigates nasal inflammation and modulates gut microbiota in allergic rhinitis mice.

Introduction: Allergic rhinitis (AR) is a respiratory immune system disorder characterized by dysregulation of immune responses. Within the context of AR, gut microbiota and its metabolites have been identified as contributors to immune modulation. These microorganisms intricately connect the respiratory and gut immune systems, forming what is commonly referred to as the gut-lung axis. Xiaoqinglong Decoction (XQLD), a traditional Chinese herbal remedy, is widely utilized in traditional Chinese medicine for the clinical treatment of AR. In this study, it is hypothesized that the restoration of symbiotic microbiota balance within the gut-lung axis plays a pivotal role in supporting the superior long-term efficacy of XQLD in AR therapy. Therefore, the primary objective of this research is to investigate the impact of XQLD on the composition and functionality of the gut microbiota in a murine model of AR. Methods: An ovalbumin-sensitized mouse model to simulate AR was utilized, the improvement of AR symptoms after medication was investigated, and high-throughput sequencing was employed to analyze the gut microbiota composition. Results: XQLD exhibited substantial therapeutic effects in AR mice, notably characterized by a significant reduction in allergic inflammatory responses, considerable alleviation of nasal symptoms, and the restoration of normal nasal function. Additionally, following XQLD treatment, the disrupted gut microbiota in AR mice displayed a tendency toward restoration, showing significant differences compared to the Western medicine (loratadine) group. Discussion: This results revealed that XQLD may enhance AR allergic inflammatory responses through the regulation of intestinal microbiota dysbiosis in mice, thus influencing the dynamics of the gut-lung axis. The proposal of this mechanism provides a foundation for future research in this area.

[Critical influencing factors on quality of traditional Chinese medicine preparations from perspective of process and equipment].

The quality of traditional Chinese medicine preparations is directly related to the safety of patients. Among the various factors, the process and corresponding critical equipment are critical factors influencing the quality of the preparations. To improve the quality of traditional Chinese medicine preparations, this article summarizes and analyzes the problems in the process links and corresponding critical equipment in the manufacturing process of traditional Chinese medicine preparations. Furthermore, a critical quality attribute evaluation system is established based on safety and effectiveness combined with the drug properties, preparation process, and preparation characteristics, providing a basis for the process and equipment improvements aimed at quality enhancement.

[Expression and significance of hypoxia-inducible factor 1α and Bcl-2/adenovirus E1B19kDa-interacting protein 3 in children with traumatic brain injury]. / ç¼ºæ°§è¯±å¯¼å› å­1α、Bcl-2/è ºç— æ¯’E1B19kDa相互作用蛋白3在儿童创伤性脑损伤中的表达及意义.

OBJECTIVES: To dynamically observe the changes in hypoxia-inducible factor 1α (HIF-1α) and Bcl-2/adenovirus E1B19kDa-interacting protein 3 (BNIP3) in children with traumatic brain injury (TBI) and evaluate their clinical value in predicting the severity and prognosis of pediatric TBI. METHODS: A prospective study included 47 children with moderate to severe TBI from January 2021 to July 2023, categorized into moderate (scores 9-12) and severe (scores 3-8) subgroups based on the Glasgow Coma Scale. A control group consisted of 30 children diagnosed and treated for inguinal hernia during the same period, with no underlying diseases. The levels of HIF-1α, BNIP3, autophagy-related protein Beclin-1, and S100B were compared among groups. The predictive value of HIF-1α, BNIP3, Beclin-1, and S100B for the severity and prognosis of TBI was assessed using receiver operating characteristic (ROC) curves. RESULTS: Serum levels of HIF-1α, BNIP3, Beclin-1, and S100B in the TBI group were higher than those in the control group (P<0.05). Among the TBI patients, the severe subgroup had higher levels of HIF-1α, BNIP3, Beclin-1, and S100B than the moderate subgroup (P<0.05). Correlation analysis showed that the serum levels of HIF-1α, BNIP3, Beclin-1, and S100B were negatively correlated with the Glasgow Coma Scale scores (P<0.05). After 7 days of treatment, serum levels of HIF-1α, BNIP3, Beclin-1, and S100B in both non-surgical and surgical TBI patients decreased compared to before treatment (P<0.05). ROC curve analysis indicated that the areas under the curve for predicting severe TBI based on serum levels of HIF-1α, BNIP3, Beclin-1, and S100B were 0.782, 0.835, 0.872, and 0.880, respectively (P<0.05), and for predicting poor prognosis of TBI were 0.749, 0.775, 0.814, and 0.751, respectively (P<0.05). CONCLUSIONS: Serum levels of HIF-1α, BNIP3, and Beclin-1 are significantly elevated in children with TBI, and their measurement can aid in the clinical assessment of the severity and prognosis of pediatric TBI.

Fault Diagnosis Method for Rolling Bearings Based on Grey Relation Degree.

Aiming at the difficult problem of extracting fault characteristics and the low accuracy of fault diagnosis throughout the full life cycle of rolling bearings, a fault diagnosis method for rolling bearings based on grey relation degree is proposed in this paper. Firstly, the subtraction-average-based optimizer is used to optimize the parameters of the variational mode decomposition algorithm. Secondly, the vibration signals of bearings are decomposed by using the optimized results, and the feature vector of the intrinsic mode function component corresponding to the minimum envelope entropy is extracted. Finally, the grey proximity and similarity relation degree based on standard distance entropy are weighted to calculate the grey comprehensive relation degree between the feature vector of vibration signals and each standard state. By comparing the results, the diagnosis of different fault states and degrees of rolling bearings is realized. The XJTU-SY dataset was used for experimentation, and the results show that the proposed method achieves a diagnostic accuracy of 95.24% and has better diagnosis performance compared to various algorithms. It provides a reference for the fault diagnosis of rolling bearings throughout the full life cycle.