Ameliorative effect of total ginsenosides from heat-treated fresh ginseng against cyclophosphamide-induced liver injury in mice.

This study evaluated the effect of heat treatment on the conversion of ginsenoside and the ameliorative effect of heat-treated total ginsenoside (HG) from fresh ginseng on cyclophosphamide (CTX)-induced liver injury. LC-MS analysis revealed that the content of rare ginsenosides increased markedly after heat treatment. HG significantly attenuated CTX-induced hepatic histopathological injury in mice. Western blotting analysis showed that untreated total ginsenoside (UG) and HG regulated the Nrf2/HO-1 and TLR4/MAPK pathways. Importantly, these results may be relevant to the modulation of the intestinal flora. UG and HG significantly increased the short-chain fatty acids (SCFAs)-producing bacteria Lactobacillus and reduced the LPS-producing bacteria Bacteroides and Parabacteroides. These changes in intestinal flora affected the levels of TNF-α, LPS and SCFAs. In short, UG and HG alleviated CTX-induced liver injury by regulating the intestinal flora and the LPS-TLR4-MAPK pathway, and HG was more effective. HG has the potential to be a functional food that can alleviate chemical liver injury.

Highly sensitive humidity sensor based on composite film of partially reduced graphene oxide and bacterial cellulose.

Breathing is an important physiological activity of human body, which not only reflects the state of human movement, but also is one of the important health indicators. Breathing can change the concentration of water molecules, so monitoring humidity has gradually become a hot topic in modern research. In this study, a humidity sensing composite film with high sensitivity and short response time was made by using the mixture of graphene oxide (GO) and bacterial cellulose (BC) with simple dry film-forming method. L-ascorbic acid was used as reducing agent to reduce GO and improve the conductivity of GO/BC composite film (BG). The influence of different BC contents and the different reduction degree on the resistance change rate of composite film was investigated in details. The maximum resistance change rate of partially reduced BG humidity sensitive composite film reached up to 94%, and the response and recovery time were 13 s and 47 s respectively. Furthermore, the sensor shows obvious resistance change in noncontact sensing test and different breathing states. This kind of humidity sensitive film with fast response and high sensitivity has great potential in human health monitoring and noncontact sensing, and is of great significance in promoting health detection and intelligent life.

Complete Genome Sequence Analysis of Bacillus subtilis MC4-2 Strain That against Tobacco Black Shank Disease.

The MC4-2 bacterium strain was isolated and purified from the Periplaneta americana intestine as a biocontrol agent with good antagonistic effect against the pathogens of a soil-borne disease called tobacco black shank. The MC4-2 strain was found to have good broad-spectrum inhibition by plate stand-off test. Based on 16S rRNA and gyrB genes, ANI analysis, and other comparative genomics methods, it was determined that the MC4-2 strain was Bacillus subtilis. The complete genome sequence showed that the genome size was 4,076,630 bp, the average GC content was 43.78%, and the total number of CDSs was 4,207. Genomic prediction analysis revealed that a total of 145 genes were annotated by the CAZy, containing mainly GH and CE enzymes that break down carbohydrates such as glucose, chitin, starch, and alginate, and a large number of enzymes involved in glycosylation were present. A total of ten secondary metabolite clusters were predicted, six clusters of which were annotated as surfactin, bacillaene, fengycin, bacillibactin, subtilosin A, and bacilysin. The present investigation found the biological control mechanism of B. subtilis MC4-2, which provides a strong theoretical basis for the best use of this strain in biological control methods and provides a reference for the subsequent development of agents of this bacterium.

Matching actions to needs: shifting policy responses to the changing health needs of Chinese children and adolescents.

China is home to the second largest population of children and adolescents in the world. Yet demographic shifts mean that the government must manage the challenge of fewer children with the needs of an ageing population, while considering the delicate tension between economic growth and environmental sustainability. We mapped the health problems and risks of contemporary school-aged children and adolescents in China against current national health policies. We involved multidisciplinary experts, including young people, with the aim of identifying actionable strategies and specific recommendations to promote child and adolescent health and wellbeing. Notwithstanding major improvements in their health over the past few decades, contemporary Chinese children and adolescents face distinct social challenges, including high academic pressures and youth unemployment, and new health concerns including obesity, mental health issues, and sexually transmitted infections. Inequality by gender, geography, and ethnicity remains a feature of health risks and outcomes. We identified a mismatch between current health determinants, risks and outcomes, and government policies. To promote the health of children and adolescents in China, we recommend a set of strategies that target government-led initiatives across the health, education, and community sectors, which aim to build supportive and responsive families, safe communities, and engaging and respectful learning environments. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Enhancing scanning electron microscopy imaging quality of weakly conductive samples through unsupervised learning.

Scanning electron microscopy (SEM) is a crucial tool for analyzing submicron-scale structures. However, the attainment of high-quality SEM images is contingent upon the high conductivity of the material due to constraints imposed by its imaging principles. For weakly conductive materials or structures induced by intrinsic properties or organic doping, the SEM imaging quality is significantly compromised, thereby impeding the accuracy of subsequent structure-related analyses. Moreover, the unavailability of paired high-low quality images in this context renders the supervised-based image processing methods ineffective in addressing this challenge. Here, an unsupervised method based on Cycle-consistent Generative Adversarial Network (CycleGAN) was proposed to enhance the quality of SEM images for weakly conductive samples. The unsupervised model can perform end-to-end learning using unpaired blurred and clear SEM images from weakly and well-conductive samples, respectively. To address the requirements of material structure analysis, an edge loss function was further introduced to recover finer details in the network-generated images. Various quantitative evaluations substantiate the efficacy of the proposed method in SEM image quality improvement with better performance than the traditional methods. Our framework broadens the application of artificial intelligence in materials analysis, holding significant implications in fields such as materials science and image restoration.

Physicochemical properties and in vitro digestibility of ginseng starches under citric acid-autoclaving treatment.

In this study, the effects of citric acid-autoclaving (CA-A) treatment on physicochemical and digestive properties of the native ginseng starches were investigated. The results showed that ginseng starch exhibited a B-type crystal structure with a low onset pasting temperature of 44.23 ± 0.80 °C, but high peak viscosity and setback viscosity of 5897.34 ± 53.72 cP and 692.00 ± 32.36 cP, respectively. The granular morphology, crystal and short-range ordered structure of ginseng starches were destroyed after CA-A treatment. The more short-chain starches were produced, resulting in the ginseng starches solubility increased. In addition, autoclaving, citric acid (CA) and CA-A treatment promoted polymerization and recrystallization of starch molecules, increased the proportion of amylopectin B1, and B3 chains, and improved molecular weight and resistant starch (RS) content of ginseng starches. The most significant multi-scale structural change was induced by CA-A treatment, which reduced the relative crystallinity of ginseng starch from 28.26 ± 0.24 % to 2.75 ± 0.08 %, and increased the content of RS to 54.30 ± 0.14 %. These findings provided a better understanding of the structure and properties of Chinese ginseng starches and offered new ideas for the deep processing of ginseng foods.

A Multi-foci Sparse-Aperture Metalens.

Multi-foci lenses are essential components for optical communications, virtual reality display and microscopy, yet the bulkiness of conventional counterparts has significantly hindered their widespread applications. Benefiting from the unprecedented capability of metasurfaces in light modulation, metalenses are able to provide multi-foci functionality with a more compact footprint. However, achieving imaging quality comparable to that of corresponding single-foci metalenses at each focal point poses a challenge for existing multi-foci metalenses. Here, a polarization-independent all-dielectric multi-foci metalens is proposed and experimentally demonstrated by spatially integrating single-foci optical sparse-aperture sub-metalenses. Such design enables the metalens to generate multiple focal points, while maintaining the ability to capture target information comparable to that of a single-foci metalens. The proposed multi-foci metalens is composed of square-nanohole units array fabricated by two-photon polymerization. The focusing characteristic and imaging capability are demonstrated upon the illumination of an unpolarized light beam. This work finds a novel route toward multi-foci metalenses and may open a new avenue for dealing with the trade-off between multi-foci functionality and high-quality imaging performance.

Ginseng Glucosyl Oleanolate from Ginsenoside Ro, Exhibited Anti-Liver Cancer Activities via MAPKs and Gut Microbiota In Vitro/Vivo.

Ginseng is widely recognized for its diverse health benefits and serves as a functional food ingredient with global popularity. Ginsenosides with a broad range of pharmacological effects are the most crucial active ingredients in ginseng. This study aimed to derive ginseng glucosyl oleanolate (GGO) from ginsenoside Ro through enzymatic conversion and evaluate its impact on liver cancer in vitro and in vivo. GGO exhibited concentration-dependent HepG2 cell death and markedly inhibited cell proliferation via the MAPK signaling pathway. It also attenuated tumor growth in immunocompromised mice undergoing heterograft transplantation. Furthermore, GGO intervention caused a modulation of gut microbiota composition by specific bacterial populations, including Lactobacillus, Bacteroides, Clostridium, Enterococcus, etc., and ameliorated SCFA metabolism and colonic inflammation. These findings offer promising evidence for the potential use of GGO as a natural functional food ingredient in the prevention and treatment of cancer.

Direct exposure to CpG and specific antigens mitigate airway allergy through modulating dendritic cell properties.

BACKGROUND: CpG oligodeoxynucleotide (CpG-ODN; CpG, in short) has been employed as an adjuvant in allergen specific immunotherapy (AIT) to treat allergic diseases. The underlying mechanism needs to be further explained. The aim of this study is to examine the mechanism by which CpG and dust mite extracts (DME, a specific antigen) alleviate experimental airway allergy. METHODS: DME was used as the specific allergen to establish an airway allergy mouse model. The mice were directly exposed to DME and CpG through nasal instillations (the CpG.DME therapy). The response of DCs and allergic responses in the airways were assessed using immunological approaches. RESULTS: The airway allergy reaction was effectively suppressed by CpG.DME therapy. The administration of CpG or DME alone did not have any significant suppressive effects on the airway allergic response. Direct exposure to CpG.DME induced type 1 DCs (DC1s) and plasmacytoid DCs (pDCs), while CpG alone induced DC1s and DME alone induced DC2s in the airway tissues. Both DC1s and pDCs were required for the induction of type 1 regulatory T cells in the airway tissues by CpG.DME therapy. Depletion of either pDCs or DC1s abolished the induction of Tr1 cells, and abolished the suppressive effects on airway allergic response by the CpG.DME therapy. CONCLUSIONS: Direct exposure to CpG.DME induces DC1s and pDCs in the airway tissues. DC1s in synergy with pDCs induce type 1 regulatory T cells. The CpG.DME therapy is effective in suppressing allergic responses in mice with airway allergy.

Identification of differentially expressed miRNAs in plasma exosomes from patients with early-onset pre-eclampsia using next generation sequencing.

Pre-eclampsia (PE), a major cause of perinatal morbidity and mortality, accounts for up to 14 % mortality of maternal and 18 % of fetal or infant mortalities. However, the pathogenesis process of PE remains unclear. The aim of this study was to identify differentially expressed microRNAs (miRNAs) in the peripheral blood exosomes of early-onset PE patients versus healthy pregnant women using high-throughput sequencing, and to find candidate miRNAs as molecular markers. Methods: Peripheral blood samples were collected from five preeclamptic patients and five healthy women. Exosomal miRNAs were sequenced using the Illumina HiSeq4000 sequencing platform. The target gene prediction, biological function enrichment, and signaling pathway prediction of the miRNAs with significant differences were carried out using the Starbase database software, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively. Our results showed 65 significantly differentially expressed miRNAs in the exosomes of early-onset PE patients compared to control group, with 17 up-regulated and 48 down-regulated (P < 0.05). A total of 2231 target genes were predicted for all differentially expressed miRNAs. Biological functions enriched by these target genes were mainly associated with Ras protein signal transduction, GTPase-mediated signal transduction regulation, histone modification, and ß-transforming growth factor regulatory process. Key regulatory signaling pathways included TGF-ß signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, tumor necrosis factor signaling pathway and EGFR tyrosine kinase inhibition signaling pathways. QPCR validation in 40 independent samples for 10 miRNAs, identified three miRNAs were confirmed in the second population. MIR7151 was a most significant differentially expressed miRNAs, and predicted its downstream regulatory gene, KCNQ10T1, using Starbase software. There were significant differences in miRNA expression profiles between peripheral blood exosomes of early-onset PE patients and normal pregnant women, suggesting that these miRNAs may contribute to the pathophysiology of early-onset PE by regulating various biological functions and signaling pathways.

Bacterial cellulose/multi-walled carbon nanotube composite films for moist-electric energy harvesting.

Generation of renewable and clean electricity energy from ubiquitous moisture for the power supply of portable electronic devices has become one of the most promising energy collection methods. However, the modest electrical output and transient power supply characteristics of existing moist-electric generator (MEG) severely limit its commercial application, leading to an urgent demand of developing a MEG with high electrical output and continuous power generation capacity. In this work, it is demonstrated that a flexible bacterial cellulose (BC)/Multi-walled carbon nanotube (MWCNT) double-layer (BM-dl) film prepared by vacuum filtration can maintain the moisture concentration difference in the film MEG. Unlike previous studies on cellulose based MEG, BM-dl film has a heterogeneous structure, resulting in a maximum output power density of 0.163 µW/cm2, an extreme voltage of 0.84 V, and current of 2.21 µA at RH = 90 %. BM-dl MEG can generate a voltage of 0.55 V continuously for 45 h in a natural environment (RH = 63-77 %, T = 26-27 °C), which is in a leading level among existing reported cellulose-based MEGs. In summary, this study provides new ideas for innovative design of MEG, which is highly competitive in terms of energy supply for the Internet of Things and wearable devices.

From transients to permanent residents: the existence of obligate aerobic microorganisms in the goat rumen.

The rumen serves as a complex ecosystem, harboring diverse microbial communities that play crucial ecological roles. Because previous studies have predominantly focused on anaerobic microorganisms, limited attention has been given to aerobic microorganisms in the goat rumen. This study aims to explore the diversity of aerobic microorganisms in the rumen and understand their niche and ecological roles. Rumen fluid samples were collected from 6 goats at different time points post-morning feeding. pH, NH3-N, and volatile fatty acid (TVFA) concentrations were measured, while In vitro cultivation of aerobic microorganisms was performed using PDA medium. Internal Transcribed Spacer (ITS) and 16S sequencing unveiled microbial diversity within the rumen fluid samples. Evidence of obligate aerobic microorganisms in the goat rumen suggests their potential contribution to ecological functionalities. Significantly, certain aerobic microorganisms exhibited correlations with TVFA levels, implying their involvement in TVFA metabolism. This study provides evidence of the existence and potential ecological roles of obligate aerobic microorganisms in the goat rumen. The findings underscore the significance of comprehensively deciphering goat rumen microbial communities and their interactions, with aerobes regarded as permanent residents rather than transients. These insights form a solid foundation for advancing our understanding of the intricate interplay between goat and their aerobic microorganisms in the rumen.

Raman signal optimization based on residual network adaptive focusing.

Due to its high sensitivity and specificity, Micro-Raman spectroscopy has emerged as a vital technique for molecular recognition and identification. As a weakly scattered signal, ensuring the accurate focus of the sample is essential for acquiring high quality Raman spectral signal and its analysis, especially in some complex microenvironments such as intracellular settings. Traditional autofocus methods are often time consuming or necessitate additional hardware, limiting real-time sample observation and device compatibility. Here, we propose an adaptive focusing method based on residual network to realize rapid and accurate focusing on Micro-Raman measurements. Using only a bright field image of the sample acquired on any image plane, we can predict the defocus distance with a residual network trained by Resnet50, in which the focus position is determined by combining the gradient and discrete cosine transform. Further, detailed regional division of the bright field map used for characterizing the height variation of actual sample surface is performed. As a result, a focus prediction map with 1µm accuracy is obtained from a bright field image in 120 ms. Based on this method, we successfully realize Raman signal optimization and the necessary correction of spectral information. This adaptive focusing method based on residual network is beneficial to further enhance the sensitivity and accuracy of Micro-Raman spectroscopy technology, which is of great significance in promoting the wide application of Raman spectroscopy.

Multi-Omics Approach Reveals OsPIL1 as a Regulator Promotes Rice Growth, Grain Development, and Blast Resistance.

Rice (Oryza sativa) is a crucial crop, achieving high yield concurrent pathogen resistance remains a challenge. Transcription factors play roles in growth and abiotic tolerance. However, rice phytochrome-interacting factor-like 1 (OsPIL1) in pathogen resistance and agronomic traits remains unexplored. We generated OsPIL1 overexpressing (OsPIL1 OE) rice lines and evaluated their impact on growth, grain development, and resistance to Magnaporthe oryzae. Multiomics analysis (RNA-seq, metabolomics, and CUT&Tag) and RT-qPCR validated OsPIL1 target genes and key metabolites. In the results, OsPIL1 OE rice lines exhibited robust growth, longer grains, and enhanced resistance to M. oryzae without compromising growth. Integrative multiomics analysis revealed a coordinated regulatory network centered on OsPIL1, explaining these desirable traits. OsPIL1 likely acts as a positive regulator, targeting transcriptional elements or specific genes with direct functions in several biological programs. In particular, a range of key signaling genes (phosphatases, kinases, plant hormone genes, transcription factors), and metabolites (linolenic acid, vitamin E, trigonelline, d-glucose, serotonin, choline, genistein, riboflavin) contributed to enhanced rice growth, grain size, pathogen resistance, or a combination of these traits. These findings highlight OsPIL1's regulatory role in promoting important traits and provide insights into potential strategies for rice breeding.

Understanding the application of covalent adaptable networks in self-repair materials based on molecular simulation.

Covalent adaptable networks (CANs) are widely used in the field of self-repair materials. They are a group of covalently cross-linked associative polymers that undergo reversible chemical reactions, and can be further divided into dissociative CANs (Diss-CANs) and associative CANs (Asso-CANs). Self-repair refers to the ability of a material to repair itself without external intervention, and can be classified into self-adhesion and self-healing according to the utilization of open stickers. Unlike conventional materials, the viscoelastic properties of CANs are influenced by both the molecular structure and reaction kinetics, ultimately affecting their repair performance. To gain deeper insight into the repair mechanism of CANs, we conducted simulations by using the hybrid MC/MD algorithm, as previously proposed in our research. Interestingly, we observed a significant correlation between reaction kinetics and repair behavior. Asso-CANs exhibited strong mechanical strength and high creep resistance, rendering them suitable as self-adhesion materials. On the other hand, Diss-CANs formed open stickers that facilitated local relaxation, aligning perfectly with self-healing processes. Moreover, the introduction of crosslinkers in the form of small molecules enhanced the repair efficiency. Theoretically, it was found that the repair timescale of Asso-CANs is slower than that of Diss-CANs with identical molecular structures. Our study not only clarifies the similarities and differences between Diss-CANs and Asso-CANs in terms of their self-repairing capabilities, but more importantly, it provides valuable insights guiding the effective utilization of CANs in the development of self-repair materials.

The cyclic AMP (cAMP) phosphodiesterase CpdA required for growth, biofilm formation, motility and pathogenicity of Edwardsiella piscicida.

Edwardsiella piscicida is a severe fish pathogen with wide host range, causing the huge economic losses in the aquaculture industry. Cyclic adenosine monophosphate (cAMP) as an important second messenger regulates the physiological and behavioral responses to environmental cues in eukaryotic and prokaryotic. The intracellular level of cAMP for effective activity is tightly controlled by the synthesis of adenylate cyclase, excretion and degradation of phosphodiesterase. In this study, we identified and characterized a class III cAMP phosphodiesterase, named as CpdA, in the E. piscicida. To investigate the role of CpdA in the physiology and pathogenicity, we constructed the in-frame deletion mutant of cpdA of E. piscicida, TX01ΔcpdA. The results showed that TX01ΔcpdA accumulated the higher intracellular cAMP concentration than TX01, indicating that CpdA exerted the hydrolysis of cAMP. In addition, compared to the TX01, the TX01ΔcpdA slowed growth rate, diminished biofilm formation and lost motility. More importantly, pathogenicity analysis confirmed that TX01ΔcpdA significantly impaired the ability of invading the epithelial cells, reproduction in macrophages, tissues dissemination and lethality for healthy tilapias. The most of lost properties of TX01ΔcpdA were restored partially or fully by the introduction of cpdA gene. These results suggest that cpdA is required for regulation of the physiology and virulence of E. piscicida.

Whole-genome sequencing and RNA sequencing analysis reveals novel risk genes and differential expression patterns in hepatoblastoma.

Hepatoblastoma (HB) is an uncommon malignant liver cancer primarily affecting infants and children, characterized by the presence of tissue that resembling fetal hepatocytes, mature liver cells or bile duct cells. The primary symptom in affected children is abdominal lumps. HB constitutes approximately 28% of all liver tumors and two-thirds of liver malignancies in the pediatric and adolescent population. Despite its high prevalence, the underlying mechanism of HB pathogenesis remain largely unknown. To reveal the genetic alternations associated with HB, we conducted a comprehensive genomic study using whole-genome sequencing (WGS) and RNA sequencing (RNA-seq) techniques on five HB patients. We aimed to use WGS to identify somatic variant loci associated with HB, including single nucleotide polymorphisms (SNPs), insertions and deletions (Indels), and copy number variations (CNVs). Notably, we found deleterious mutation in CTNNB1, AXIN2 and PARP1, previously implicated in HB. In addition, we discovered multiple novel genes potentially associated with HB, including BRCA2 and GPC3 which require further functional validation to reveal their contributions to HB development. Furthermore, the American College of Medical Genetics and Genomics (ACMG) analysis identified the ABCC2 gene was the pathogenic gene as a potential risk gene linked with HB. To study the gene expression patterns in HB, we performed RNA-seq analysis and qPCR validation to reveal differential expression of four candidate genes (IGF1R, METTL1, AXIN2 and TP53) in tumors compared to nonneoplastic liver tissue in HB patients (P-Val < 0.01). These findings shed lights on the molecular mechanisms underlying HB development and facilitate to advance future personalized diagnosis and therapeutic interventions of HB.

Bacillus subtilis YZ-1 surfactins are involved in effective toxicity against agricultural pests.

BACKGROUND: Insect pests negatively affect crop quality and yield. The excessive use of chemical pesticides has serious impacts on the environment and food safety. Therefore, development of effective management strategies in the form of bio-agents have important agricultural applications. Tenebrio molitor, a storage pest, causes losses of grains, medicinal materials, and various agricultural and related products in the warehouse. Bacillus subtilis YZ-1 isolated from naturally deceased Pieris rapae has been found to exhibit significant toxicity against T. molitor. RESULTS: Treatment with B. subtilis YZ-1 fermentation broth resulted in a 90-95% mortality rate of T. molitor within 36 h post-treatment, indicating some active substances may have insecticidal activity in the bacterial supernatant. A bioactivity-guided fractionation method was used to isolate the insecticidal compounds from YZ-1, which led to the identification of surfactins. Additionally, a surfactin deletion mutant YZ-1△srfAA was constructed and the surfactin production by the mutant YZ-1△srfAA was verified through liquid chromatography-mass spectrometry (LC-MS). Further, YZ-1△srfAA exhibited loss of insecticidal activity against T. molitor, Plutella xylostella and Achelura yunnanensis. The insecticidal activity and surfactins contents of several strains of Bacillus sp. were also tested and correlation was found between varying surfactins yield and insecticidal activity exhibited by different strains. CONCLUSION: Conclusively, our results suggest that B. subtilis YZ-1 may provide a novel approach for plant protection against agricultural pests. © 2023 Society of Chemical Industry.

Sodium glucose cotransporter2 inhibitors for type 1 diabetes mellitus: A meta-analysis of randomized controlled trials.

AIMS: Sodium glucose cotransporter2 (SGLT2) inhibitors are controversial in the treatment of type 1 diabetes mellitus (T1DM). This study is a systematic evaluation of the safety of SGLT2 inhibitors usage in T1DM. METHODS: Comprehensive literature search in six databases from inception to September 2022. Randomized controlled trials (RCTs) of T1DM treated with SGLT2 inhibitor vs. placebo were included. Data were extracted from the literature that met the inclusion criteria. After quality evaluation by the Cochrane risk bias assessment tool, meta-analysis was performed using Revman 5.4 and Stata 17.1. RESULTS: The study consisted of 16 RCTs with 7192 patients. The results indicated that SGLT2inhibitors reduce glycated hemoglobin (HbA1c, Mean difference (MD)- 0.29%, P < 0.05), fasting plasma glucose (FPG, MD-0.85 mmol/L, P < 0.05), mean amplitude of glucose excursions (MAGE, 15.75 mg/dL, P < 0.05), body weight (MD-3.49 kg, P < 0.05), and total insulin dosage (MD-7.14 IU/day, P < 0.05). Furthermore, cautious SGLT2 inhibitors did not induce the risk of hypoglycemia (RR1.00, P = 0.86), urinary tract infections (RR1.02, P = 0.085), and diarrhea (RR1.34, P = 0.523). CONCLUSION: Based on this meta-analysis, SGLT22 inhibitors reduce insulin dosage without increasing the risk of hypoglycemia and diabetic ketoacidosis for type 1 diabetes mellitus in 1month.

Unbiased Single-Cell Sequencing of Hematopoietic and Immune Cells from Aplastic Anemia Reveals the Contributors of Hematopoiesis Failure and Dysfunctional Immune Regulation.

Aplastic anemia (AA) is a bone marrow (BM) failure syndrome mediated by hyperactivated T-cells with heterogeneous pathogenic factors. The onset of BM failure cannot be accurately determined in humans; therefore, exact pathogenesis remains unclear. In this study, a cellular atlas and microenvironment interactions is established using unbiased single-cell RNA-seq, along with multi-omics analyses (mass cytometry, cytokine profiling, and oxidized fatty acid metabolomics). A new KIR+ CD8+ regulatory T cells (Treg) subset is identified in patients with AA that engages in immune homeostasis. Conventional CD4+ T-cells differentiate into highly differentiated T helper cells with type 2 cytokines (IL-4, IL-6, and IL-13), GM-SCF, and IL-1ß. Immunosuppressive homeostasis is impaired by enhanced apoptosis of activated Treg cells. Pathological Vδ1 cells dominated the main fraction of γδ T-cells. The B/plasma, erythroid, and myeloid lineages also exhibit substantial pathological features. Interactions between TNFSF12-TNFRSF12A, TNF-TNFRSF1A, and granzyme-gasdermin are associated with the cell death of hematopoietic stem/progenitor (HSPCs), Treg, and early erythroid cells. Ferroptosis, a major driver of HSPCs destruction, is identified in patients with AA. Furthermore, a case of twins with AA is reported to enhance the persuasiveness of the analysis. These results collectively constitute the cellular atlas and microenvironment interactions in patients with AA and provide novel insights into the development of new therapeutic opportunities.