Metals/bisulfite system involved generation of 24-sulfonic-25-ene ginsenoside Rg1, a potential quality control marker for sulfur-fumigated ginseng.

Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.

[Clinical comprehensive evaluation of Shexiang Tongxin Dropping Pills].

Based on literature and questionnaire research, related evidence and related data on Shexiang Tongxin Dropping Pills were collected in terms of safety, effectiveness, economy, innovation, suitability, and accessibility. In addition, multi-criteria decision analysis(MCDA) model was used to comprehensively evaluate the clinical value of Shexiang Tongxin Dropping Pills. Quality control was carried out strictly based on evidence-based medicine evaluation. Shexiang Tongxin Dropping Pills were recommended for stable fatigue angina of coronary heart disease with Qi deficiency and blood stasis by guidelines and experts. The conventional treatment of western medicine adds Shexiang Tongxin Dropping Pills to reduce the frequency of angina attacks, shorten the duration, improve exercise tolerance, and improve the quality of life and Chinese symptoms, and the effectiveness is rated as grade A. Adverse reactions are mostly general adverse reactions, and no serious adverse reactions have been reported, consistent with the known risks listed in the instruction for adverse events, contraindications, and precautions. The safety is rated as grade A, and the daily cost is 7.74 yuan. The cost-effectiveness shows that it is a treatment regimen with pharmacoeconomic advantages, and the economic performance is rated as grade A. According to specialist research, Shexiang Tongxin Dropping Pills have good clinical innovation and service innovation, and innovation is rated as grade A. There are no special storage conditions, medicinal material ingredients, or other restrictions, and the clinical use meets the specifications of the medication guidelines. The suitability is rated as grade A. The price level, availability, and affordability of drugs are generally good, and the accessibility is rated as grade A. The clinical value of Shexiang Tongxin Dropping Pills is great.

Regulating the Electron Distribution of Metal-Oxygen for Enhanced Oxygen Stability in Li-rich Layered Cathodes.

Li-rich Mn-based layered oxides (LLO) hold great promise as cathode materials for lithium-ion batteries (LIBs) due to their unique oxygen redox (OR) chemistry, which enables additional capacity. However, the LLOs face challenges related to the instability of their OR process due to the weak transition metal (TM)-oxygen bond, leading to oxygen loss and irreversible phase transition that results in severe capacity and voltage decay. Herein, a synergistic electronic regulation strategy of surface and interior structures to enhance oxygen stability is proposed. In the interior of the materials, the local electrons around TM and O atoms may be delocalized by surrounding Mo atoms, facilitating the formation of stronger TM─O bonds at high voltages. Besides, on the surface, the highly reactive O atoms with lone pairs of electrons are passivated by additional TM atoms, which provides a more stable TM─O framework. Hence, this strategy stabilizes the oxygen and hinders TM migration, which enhances the reversibility in structural evolution, leading to increased capacity and voltage retention. This work presents an efficient approach to enhance the performance of LLOs through surface-to-interior electronic structure modulation, while also contributing to a deeper understanding of their redox reaction.

Potential Therapeutic Targets in Myeloid Cell Therapy for Overcoming Chemoresistance and Immune Suppression in Gastrointestinal Tumors.

In the tumor microenvironment (TME), myeloid cells play a pivotal role. Myeloid-derived immunosuppressive cells, including tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), are central components in shaping the immunosuppressive milieu of the tumor. Within the TME, a majority of TAMs assume an M2 phenotype, characterized by their pro-tumoral activity. These cells promote tumor cell growth, angiogenesis, invasion, and migration. In contrast, M1 macrophages, under appropriate activation conditions, exhibit cytotoxic capabilities against cancer cells. However, an excessive M1 response may lead to pro-tumoral inflammation. As a result, myeloid cells have emerged as crucial targets in cancer therapy. This review concentrates on gastrointestinal tumors, detailing methods for targeting macrophages to enhance tumor radiotherapy and immunotherapy sensitivity. We specifically delve into monocytes and tumor-associated macrophages' various functions, establishing an immunosuppressive microenvironment, promoting tumorigenic inflammation, and fostering neovascularization and stromal remodeling. Additionally, we examine combination therapeutic strategies.

A reassessment of trends and rural-urban/regional differences in the total fertility rate in China, 2000-2020: analyses of the 2020 national census data.

The decline in the total fertility rate (TFR) is a key driver of population change and has important implications for population health and social development. However, China's TFR has been a considerable controversy due to a lack of high-quality data. Therefore, this study used the 2020 national population census of China (NPCC) data and reverse survival method to reassess temporal trends in the TFRs and to reexamine rural-urban differences and regional variations in TFRs from 2000 to 2020 in China. Overall, there were significant gaps between the estimated and reported TFRs before 2020, and the estimated TFRs based on the 2020 NPCC data remained higher than the reported TFRs from government statistics. Although TFRs rebounded shortly in the years after the two-child policy, they have shown a wavelike decline since 2010. Additionally, the estimated TFRs fluctuated below 1.5 children per woman in urban areas compared to above 1.8 in rural areas, but the rural-urban differences continued to decrease. Regarding geographic regional variations, the estimated TFRs in all regions displayed a declining trend during 2010-2020, especially in rural areas. Large decreases of over 25% in TFRs occurred in the north, east, central, and northwest regions. In addition to changing the birth policy, the government and society should adopt comprehensive strategies, including reducing the costs of marriage, childbearing, and child education, as well as promoting work-family balance, to encourage and increase fertility levels.

MiR-497-5p regulates ox-LDL-induced dysfunction in vascular endothelial cells by targeting VEGFA/p38/MAPK pathway in atherosclerosis.

Background: The impairment of endothelial cells triggered by oxidized low-density lipoprotein (ox-LDL) stands as a critical event in the advancement of atherosclerosis (AS). MiR-497-5p has been recognized as a potential predictor for AS, but its precise involvement in ox-LDL-induced endothelial cell dysfunction remains to be elucidated. Methods: An in vitro AS cell model was established by exposing human umbilical vein endothelial cells (HUVECs) to 100 µg/mL ox-LDL for 24 h. The assessment of endothelial cell function included evaluating cell viability, caspase-3 activity, inflammatory factors, and oxidative markers. Molecular mechanisms were elucidated through quantitative real-time PCR, Western blot analysis, and luciferase reporter assays. Results: Our investigation revealed that exposure to ox-LDL led to an upregulation in miR-497-5p and p-p38 levels, while downregulating the expression of vascular endothelial growth factor A (VEGFA) and phosphorylated (p)-endothelial nitric oxide synthase (p-eNOS) in HUVECs. Ox-LDL exposure resulted in decreased cell viability and angiogenic capacity, coupled with increased apoptosis, inflammation, and oxidative stress in HUVECs, partially mediated by the upregulation of miR-497-5p. We confirmed VEGFA as a direct target of miR-497-5p. Interfering with VEGFA expression significantly reversed the effects mediated by miR-497-5p silencing in HUVECs exposed to ox-LDL. Conclusions: In summary, our findings demonstrate that miR-497-5p exacerbates ox-LDL-induced dysfunction in HUVECs through the activation of the p38/MAPK pathway, mediated by the targeting of VEGFA.

Wound healing rates in COPD patients undergoing traditional pulmonary rehabilitation versus tailored Wound-Centric interventions.

This comparative cross-sectional study, conducted at Shanghai Pulmonary Hospital, aimed to evaluate the efficacy of tailored wound-centric interventions (TWCI) versus traditional pulmonary rehabilitation (TPR) in enhancing wound healing in patients with chronic obstructive pulmonary disease (COPD). Enrolling 340 patients with confirmed COPD, the study randomly assigned participants to either the TWCI or TPR group for a 12-week programme. The primary outcome measured was the rate of wound healing, with secondary outcomes including changes in pulmonary function tests (PFTs) and quality of life (QoL) scores. The TWCI group received a customized programme integrating standard pulmonary rehabilitation with specific wound care strategies, such as enhanced oxygen therapy, nutritional supplementation, and infection control measures. In contrast, the TPR group underwent a conventional pulmonary rehabilitation programme without targeted wound care interventions. Wound healing rates, PFTs, and QoL scores were assessed at the end of the intervention and 3 months post-intervention. The TWCI group demonstrated a statistically significant improvement in wound healing rates compared with the TPR group. The TWCI group had a 15% higher rate of reduction in wound size, a 10% rise in complete healing rates, and a 20% drop in infection rates (p < 0.05). Specifically, TWCI group exhibited higher rates of wound size reduction, complete healing, and decreased infection rates. Additionally, long-term pulmonary function and overall quality of life improvements were more pronounced in the tailored group, underscoring the benefits of a personalized approach to managing COPD and wound care. The study concluded that integrating wound-specific care strategies with pulmonary rehabilitation significantly enhances health outcomes in COPD patients with wounds. These findings supported the adoption of customized, multidisciplinary care plans, suggesting that tailored interventions can offer a comprehensive solution to the complex needs of COPD patients, potentially redefining best practices in chronic disease management.

Regulation of Hard Segment Cluster Structures for High-performance Poly(urethane-urea) Elastomers.

Elastomers are widely used in daily life; however, the preparation of degradable and recyclable elastomers with high strength, high toughness, and excellent crack resistance remains a challenging task. In this report, a polycaprolactone-based poly(urethane-urea) elastomer is presented with excellent mechanical properties by optimizing the arrangement of hard segment clusters. It is found that long alkyl chains of the chain extenders lead to small and evenly distributed hard segment clusters, which is beneficial for improving mechanical properties. Together with the multiple hydrogen bond structure and stress-induced crystallization, the obtained elastomer exhibits a high strength of 63.3 MPa, an excellent toughness of 431 MJ m-3 and an outstanding fracture energy of 489 kJ m-2, while maintaining good recyclability and degradability. It is believed that the obtained elastomer holds great promise in various application fields and it contributes to the development of a sustainable society.

Major depressive disorder and the risk of irritable bowel syndrome: A Mendelian randomization study.

BACKGROUND: The association between major depressive disorder (MDD) and irritable bowel syndrome (IBS) has been found in observational research; however, the causative relationship between MDD and IBS remains uncertain. Using the two-sample Mendelian randomization (MR) approach, we attempted to examine the causal effect of MDD on IBS. METHODS: Independent genetic variants for MDD identified by Howard et al. based on a genome-wide meta-analysis were selected for this study. Gene-Outcome associations for IBS were gathered from UK Biobank and FinnGen databases. The MR analysis included inverse variance weighted (IVW), MR-Egger regression, weighted median, weighted mode, and MR-PRESSO sensitivity analyses. RESULTS: FinnGen database subjected to inverse variance weighted (IVW) analysis revealed that MDD may be a risk factor for the development of IBS (OR = 1.356, 95% CI: 1.125-1.632, p = 0.0013). The same finding was reached in UK Biobank for IVW (OR = 1.011, 95% CI: 1.006-1.015, p = 3.18 × 10-7 ), MR-Egger progression (OR = 1.030, 95% CI: 1.008-1.051, p = 0.007), and weighted median (OR = 1.011, 95% CI: 1.005-1.016, p = 0.0001). CONCLUSION: Our findings supported a causal relationship between MDD and IBS, which may have implications for the clinical management of IBS in individuals with MDD.

Fracture-Resistant Stretchable Materials: An Overview from Methodology to Applications.

Stretchable materials, such as gels and elastomers, are attractive materials in diverse applications. Their versatile fabrication platforms enable the creation of materials with various physiochemical properties and geometries. However, the mechanical performance of traditional stretchable materials is often hindered by the deficiencies in their energy dissipation system, leading to lower fracture resistance and impeding their broader range of applications. Therefore, the synthesis of fracture-resistant stretchable materials has attracted great interest. This review comprehensively summarizes key design considerations for constructing fracture-resistant stretchable materials, examines their synthesis strategies to achieve elevated fracture energy, and highlights recent advancements in their potential applications.

6-O-endosulfatases in tumor metastasis: heparan sulfate proteoglycans modification and potential therapeutic targets.

Metastasis is the leading cause of cancer-associated mortality. Although advances in the targeted treatment and immunotherapy have improved the management of some cancers, the prognosis of metastatic cancers remains unsatisfied. Therefore, the specific mechanisms in tumor metastasis need further investigation. 6-O-endosulfatases (SULFs), comprising sulfatase1 (SULF1) and sulfatase 2 (SULF2), play pivotal roles in the post-synthetic modifications of heparan sulfate proteoglycans (HSPGs). Consequently, these extracellular enzymes can regulate a variety of downstream pathways by modulating HSPGs function. During the past decades, researchers have detected the expression of SULF1 and SULF2 in most cancers and revealed their roles in tumor progression and metastasis. Herein we reviewed the metastasis steps which SULFs participated in, elucidated the specific roles and mechanisms of SULFs in metastasis process, and discussed the effects of SULFs in different types of cancers. Moreover, we summarized the role of targeting SULFs in combination therapy to treat metastatic cancers, which provided some novel strategies for cancer therapy.

A Common Neuronal Ensemble in the Lateral Habenula Regulates Ciprofol Anesthesia in Mice.

General anesthetics were first used over 170 years ago; however, the mechanisms of how general anesthetics induce loss of consciousness (LOC) remain unclear. Ciprofol, a novel intravenous anesthetic, has been developed by incorporating cyclopropyl into the chemical structure of propofol. This modification offers the benefits of rapid onset and minimal injection pain. Recent studies have revealed that the glutamatergic neurons of the lateral habenula (LHb) play a crucial role in modulating the LOC induced by propofol and sevoflurane. Nevertheless, the specific involvement of LHb in the anesthetic effects of ciprofol remains uncertain. Here, using targeted recombination in active populations (TRAP) combined with electroencephalogram/electromyography recordings and the righting reflex behavioral test, our study revealed that intravenous infusion of ciprofol for 1 h could lead to the induction of c-Fos expression in the LHb in mice. The combination of TRAP and gene ablation, aimed at selectively ablating ciprofol-activated neurons in the LHb, has been shown to facilitate the emergence of ciprofol anesthesia and decrease the proportion of delta waves during the emergence phase. Chemogenetic inhibition of these neurons produced a comparable effect, whereas chemogenetic activation resulted in the opposite outcome. Chemogenetic activation of ciprofol-activated neurons in the LHb delays the emergence of anesthesia and induces a deep hypnotic state during the emergence phase. Taken together, our findings suggest that LHb ciprofol-activated neurons modulate the state of consciousness and could potentially be targeted to manipulate consciousness during ciprofol anesthesia.

Inhibition of PTPRE suppresses tumor progression and improves sorafenib response in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a poor prognosis, and the efficacy of current therapeutic strategies is extremely limited in advanced diseases. Our previous study reported that protein tyrosine phosphatase receptor epsilon (PTPRE) is a promoting factor in HCC progression. In this study, our objective was to evaluate the treatment effect of PTPRE inhibitors in different HCC preclinical models. Our results indicated that the PTPRE inhibitory compound 63 (Cpd-63) inhibited tumor cell proliferation, migration, and HCC organoid growth. Mechanism research revealed that Cpd-63 could inhibit the expression of MYC and MYC targets by inhibiting the activation of SRC. Additionally, we found that Cpd-63 could improve the response of sorafenib in HCC cells. In conclusion, we demonstrated that the PTPRE inhibitors represented a potential therapeutic agent for HCC management.

Recurrence/prognosis estimation using a molecularly positive surgical margin-based model calls for alternative curative strategies in pIIIA/N2 NSCLC.

Stage pIIIA/N2 non-small cell lung cancer (NSCLC) is primarily treated by complete surgical resection combined with neoadjuvant/adjuvant therapies. However, up to 40% of patients experience tumor recurrence. Here, we studied 119 stage pIIIA/N2 NSCLC patients who received complete surgery plus adjuvant chemotherapy (CT) or chemoradiotherapy (CRT). The paired tumor and resection margin samples were analyzed using next-generation sequencing (NGS). Although all patients were classified as negative resection margins by histologic methods, NGS revealed that 47.1% of them had molecularly positive surgical margins. Patients who tested positive for NGS-detected residual tumors had significantly shorter disease-free survival (DFS) (P = 0.002). Additionally, metastatic lymph node ratio, erb-b2 receptor tyrosine kinase 2 (ERBB2) mutations, and SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4) mutations were also independently associated with DFS. We used these four features to construct a COX model that could effectively estimate recurrence risk and prognosis. Notably, mutational profiling through broad-panel NGS could more sensitively detect residual tumors than the conventional histologic methods. Adjuvant CT and adjuvant CRT exhibited no significant difference in eliminating locoregional recurrence risk for stage pIIIA/N2 NSCLC patients with molecularly positive surgical margins.

Geoengineering: proactive measures to tackle climate change.

As of 20 August, 2023, extensive parts of northern China including the capital city of Beijing had experienced arguably the hottest summer in recent years, recording consecutive days of high temperatures at or near 40°C. Against this backdrop, National Science Review (NSR) organized a web forum on a climate-related topic that needs more exposure to Chinese public and researchers alike: geoengineering. Compared to commonly-known methods to address climate change such as emission reduction, geoengineering proposes to take much more proactive measures such as injecting aerosol into the stratosphere to increase solar reflection, implementing iron fertilization in the ocean to promote microbial growth, and capturing and liquifying CO2 and injecting it directly into exhausted oil fields. The forum was hosted by Prof. Tong Zhu of Peking University with four panelists. Together, they introduced the scientific backgrounds and implementations of these proactive measures and discussed the pros and cons anticipated by researchers so far. Fei Chai () Professor, College of Ocean and Earth Sciences, Xiamen University Zhijun Jin () Professor, SONOPEC Petroleum Exploration and Production Research Institute; Dean, Institute of Energy, Peking University; Dean, Peking University Ordos Research Institute of Energy Shawchen Liu () Professor, Institute for Environmental and Climate Research, Jinan University Jianhua Xu () Associate Professor, Department of Environmental Management, College of Environmental Sciences and Engineering and Institute for Global Health and Development, Peking University Tong Zhu () (Chair) Professor, College of Environmental Sciences and Engineering, Peking University.

Tests of fit for the power function lognormal distribution.

In this study, tests of fit for the power function lognormal distribution is considered. The probability plot, probability plot correlation coefficient, and goodness-of-fit tests-the Kolmogorov-Smirnov (KS), Cramér-von Mises (CvM), and Anderson-Darling (AD) tests are provided. Tables of critical values are presented by using simulation techniques, and the AD test outperforms KS and CvM tests based on power comparisons. Finally, to illustrate these test procedures, we fit this distribution to the data which represent the survival times of 121 breast cancer patients from one hospital.

NMDA Receptors Regulate Oxidative Damage in Keratinocytes during Complex Regional Pain Syndrome in HaCaT Cells and Male Rats.

Complex regional pain syndrome (CRPS), a type of primary chronic pain, occurs following trauma or systemic disease and typically affects the limbs. CRPS-induced pain responses result in vascular, cutaneous, and autonomic nerve alterations, seriously impacting the quality of life of affected individuals. We previously identified the involvement of keratinocyte N-methyl-d-asparagic acid (NMDA) receptor subunit 2 B (NR2B) in both peripheral and central sensitizations in CRPS, although the mechanisms whereby NR2B functions following activation remain unclear. Using an in vivo male rat model of chronic post-ischemia pain (CPIP) and an in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) cell model, we discovered that oxidative injury occurs in rat keratinocytes and HaCaT cells, resulting in reduced cell viability, mitochondrial damage, oxidative damage of nucleotides, and increased apoptosis. In HaCaT cells, OGD/R induced increases in intracellular reactive oxygen species levels and disrupted the balance between oxidation and antioxidation by regulating a series of antioxidant genes. The activation of NMDA receptors via NMDA exacerbated these changes, whereas the inhibition of the NR2B subunit alleviated them. Co-administration of ifenprodil (an NR2B antagonist) and NMDA (an NMDA receptor agonist) during the reoxygenation stage did not result in any significant alterations. Furthermore, intraplantar injection of ifenprodil effectively reversed the altered gene expression that was observed in male CPIP rats, thereby revealing the potential mechanisms underlying the therapeutic effects of peripheral ifenprodil administration in CRPS. Collectively, our findings indicate that keratinocytes undergo oxidative injury in CRPS, with NMDA receptors playing regulatory roles.

Ballistic Conductance through Porphyrin Nanoribbons.

The search for long molecular wires that can transport charge with maximum efficiency over many nanometers has driven molecular electronics since its inception. Single-molecule conductance normally decays with length and is typically far below the theoretical limit of G0 (77.5 µS). Here, we measure the conductances of a family of edge-fused porphyrin ribbons (lengths 1-7 nm) that display remarkable behavior. The low-bias conductance is high across the whole series. Charging the molecules in situ results in a dramatic realignment of the frontier orbitals, increasing the conductance to 1 G0 (corresponding to a current of 20 µA). This behavior is most pronounced in the longer molecules due to their smaller HOMO-LUMO gaps. The conductance-voltage traces frequently exhibit peaks at zero bias, showing that a molecular energy level is in resonance with the Fermi level. This work lays the foundations for long, perfectly transmissive, molecular wires with technological potential.

M7G-related tumor immunity: novel insights of RNA modification and potential therapeutic targets.

RNA modifications play a pivotal role in regulating cellular biology by exerting influence over distribution features and molecular functions at the post-transcriptional level. Among these modifications, N7-methylguanosine (m7G) stands out as one of the most prevalent. Over recent years, significant attention has been directed towards understanding the implications of m7G modification. This modification is present in diverse RNA molecules, including transfer RNAs, messenger RNAs, ribosomal RNAs, and other noncoding RNAs. Its regulation occurs through a series of specific methyltransferases and m7G-binding proteins. Notably, m7G modification has been implicated in various diseases, prominently across multiple cancer types. Earlier studies have elucidated the significance of m7G modification in the context of immune biology regulation within the tumor microenvironment. This comprehensive review culminates in a synthesis of findings related to the modulation of immune cells infiltration, encompassing T cells, B cells, and various innate immune cells, all orchestrated by m7G modification. Furthermore, the interplay between m7G modification and its regulatory proteins can profoundly affect the efficacy of diverse adjuvant therapeutics, thereby potentially serving as a pivotal biomarker and therapeutic target for combinatory interventions in diverse cancer types.