Global burden of viral infectious diseases of poverty based on Global Burden of Diseases Study 2021.

BACKGROUND: Viral infectious diseases of poverty (vIDPs) remain a significant global health challenge. Despite their profound impact, the burden of these diseases is not comprehensively quantified. This study aims to analyze the global burden of six major vIDPs, including coronavirus disease 2019 (COVID-19), HIV/AIDS, acute hepatitis, dengue, rabies, and Ebola virus disease (EVD), using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021). METHODS: Following the GBD 2021 framework, we analyzed the incidence, mortality, and disability-adjusted life years (DALYs) of the six vIDPs across 204 countries and territories from 1990 to 2021. We examined the association between the Socio-Demographic Index (SDI) and the burden of vIDPs. All estimates were reported as numbers and rates per 100,000 population, calculated using the Bayesian statistical model employed by GBD 2021, with 95% uncertainty intervals (UI). RESULTS: In 2021, vIDPs caused approximately 8.7 million deaths and 259.2 million DALYs, accounting for 12.8% and 9.0% of the global all-cause totals, respectively. Globally, the burden of vIDPs varied significantly: COVID-19 caused around 7.9 million (95% UI: 7.5, 8.4) deaths and 212.0 million (95% UI 197.9, 234.7) DALYs in 2021. Acute hepatitis had the second-highest age-standardized incidence rate, with 3411.5 (95% UI: 3201.8, 3631.3) per 100,000 population, while HIV/AIDS had a high age-standardized prevalence rate, with 483.1 (95% UI: 459.0, 511.4) per 100,000 population. Dengue incidence cases rose from 26.5 million (95% UI: 3.9, 51.9) in 1990 to 59.0 million (95% UI: 15.5, 106.9) in 2021. Rabies, although reduced in prevalence, continued to pose a significant mortality risk. EVD had the lowest overall burden but significant outbreak impacts. Age-standardized DALY rates for vIDPs were significantly negatively correlated with SDI: acute hepatitis (r = -0.8, P < 0.0001), rabies (r = -0.7, P < 0.0001), HIV/AIDS (r = -0.6, P < 0.0001), COVID-19 (r = -0.5, P < 0.0001), dengue (r = -0.4, P < 0.0001), and EVD (r = -0.2, P < 0.005). CONCLUSIONS: VIDPs pose major public health challenges worldwide, with significant regional, age, and gender disparities. The results underscore the need for targeted interventions and international cooperation to mitigate the burden of these diseases. Policymakers can use these findings to implement cost-effective interventions and improve health outcomes, particularly in regions with high or increasing burdens.

Advances in the genetic etiology of female infertility.

Human reproduction is a complex process involving gamete maturation, fertilization, embryo cleavage and development, blastocyst formation, implantation, and live birth. If any of these processes are abnormal or arrest, reproductive failure will occur. Infertility is a state of reproductive dysfunction caused by various factors. Advances in molecular genetics, including cell and molecular genetics, and high-throughput sequencing technologies, have found that genetic factors are important causes of infertility. Genetic variants have been identified in infertile women or men and can cause gamete maturation arrest, poor quality gametes, fertilization failure, and embryonic developmental arrest during assisted reproduction technology (ART), and thus reduce the clinical success rates of ART. This article reviews clinical studies on repeated in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) failures caused by ovarian dysfunction, oocyte maturation defects, oocyte abnormalities, fertilization disorders, and preimplantation embryonic development arrest due to female genetic etiology, the accumulation of pathogenic genes and gene pathogenic loci, and the functional mechanism and clinical significance of pathogenic genes in gametogenesis and early embryonic development.

Identification and validation of diagnostic and prognostic biomarkers in prostate cancer based on WGCNA.

BACKGROUND: Prostate cancer (PCa) represents a significant health challenge for men, and the advancement of the disease often results in a grave prognosis for patients. Therefore, the identification of biomarkers associated with the diagnosis and prognosis of PCa holds paramount importance in patient health management. METHODS: The datasets pertaining to PCa were retrieved from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was conducted to investigate the modules specifically associated with the diagnosis of PCa. The hub genes were identified using the LASSO regression analysis. The expression levels of these hub genes were further validated by qRT-PCR experiments. Receiver operating characteristic (ROC) curves and nomograms were employed as evaluative measures for assessing the diagnostic value. RESULTS: The blue module identified by WGCNA exhibited a strong association with PCa. Six hub genes (SLC14A1, COL4A6, MYOF, FLRT3, KRT15, and LAMB3) were identified by LASSO regression analysis. Further verification confirmed that these six genes were significantly downregulated in tumor tissues and cells. The six hub genes and the nomogram demonstrated substantial diagnostic value, with area under the curve (AUC) values ranging from 0.754 to 0.961. Moreover, patients with low expression levels of these six genes exhibited elevated T/N pathological stage and Gleason score, implying a more advanced disease state. Meanwhile, their progression-free survival (PFS) was observed to be potentially poorer. Finally, a significant association could be observed between the expression of these genes and the dysregulation of immune cells, along with drug sensitivity. CONCLUSIONS: In summary, our study identified six hub genes, namely SLC14A1, COL4A6, MYOF, FLRT3, KRT15, and LAMB3, which can be utilized to establish a diagnostic model for PCa. The discovery may offer potential molecular targets for clinical diagnosis and treatment of PCa.

Integrative learning in the lens of meta-learned models of cognition: Impacts on animal and human learning outcomes.

This commentary examines the synergy between meta-learned models of cognition and integrative learning in enhancing animal and human learning outcomes. It highlights three integrative learning modes - holistic integration of parts, top-down reasoning, and generalization with in-depth analysis - and their alignment with meta-learned models of cognition. This convergence promises significant advances in educational practices, artificial intelligence, and cognitive neuroscience, offering a novel perspective on learning and cognition.

Spinal PTP1B Regulated NMDA Receptor-mediated Nociceptive Transmission and Peripheral Inflammation-induced Pain Sensitization.

Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of several pain-related substrates in spinal cord dorsal horn and are critically involved in the modification of pain transmission. The current study demonstrated that protein tyrosine phosphatase 1B (PTP1B), a unique endoplasmic reticulum-resident member of PTP family, displayed an activity-dependent increase in its protein expression and synaptic localization in spinal dorsal horn of adult male rats. PTP1B interacted with the Src Homology 3 (SH3) domain of Synapse-Associated Protein 102 (SAP102), one of the postsynaptic scaffolding proteins that anchored PTP1B at postsynaptic sites. The SAP102-tethered PTP1B augmented the synaptic transmission mediated specifically by GluN2B subunit-containing N-methyl-D-aspartate subtype glutamate receptors. Interference with PTP1B activity or disruption of its interaction with SAP102 attenuated GluN2B-mediated nociceptive transmission and ameliorated pain sensitization induced by intraplantar injection of Complete Freund's Adjuvant. These data suggested that the activity-dependent synaptic redistribution of PTP1B served as an important mechanism regulating GluN2B receptor activity and that manipulation of PTP1B synaptic targeting might represent an effective approach for the treatment of chronic inflammatory pain.

Expression and diagnostic value of serum free light chain in lung cancer. / è¡€æ¸ æ¸¸ç¦»è½»é“¾åœ¨è‚ºç™Œä¸­çš„è¡¨è¾¾åŠè¯Šæ–­ä»·å€¼.

OBJECTIVES: The expression of serum free light chain (FLC) is abnormal in various diseases, but its role in lung cancer remains unclear. This study aims to investigate the expression and diagnostic value of serum FLC in lung cancer. METHODS: A total of 80 lung cancer patients treated at Xiangdong Hospital, Hunan Normal University from January to December 2021 were selected as the lung cancer group. Another 80 healthy individuals undergoing routine physical examinations during the same period were chosen as the control group. General information and serum κFLC and λFLC levels were collected for all subjects. Clinical indicators such as serum carcinoembryonic antigen (CEA), cytokeratin fragment antigen 21-1 (CYFRA21-1) levels, tumor diameter, histological type, TNM stage, and lymph node metastasis status were recorded for lung cancer patients. The expression levels of serum FLC [κFLC, λFLC, and FLC (κ+λ)] were compared between the lung cancer group and the control group. Lung cancer patients were grouped based on gender, age, smoking history, tumor diameter, TNM stage, histological type, and lymph node metastasis to compare differences in serum κFLC and λFLC levels. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of serum FLC alone and in combination with other indicators in lung cancer. RESULTS: The expression levels of serum FLC (κ+λ) and κFLC were significantly higher in the lung cancer group than those in the control group (both P<0.001), while there was no significant difference in serum λFLC levels between the 2 groups (P>0.05). There were no significant differences in serum κFLC levels among lung cancer patients with different tumor diameters, histological types, or TNM stages (all P>0.05); however, serum κFLC levels were higher in lung cancer patients with lymph node metastasis than in those without, with statistical significance (P=0.033). There were no significant differences in serum λFLC levels based on tumor diameter or histological type (both P>0.05), but serum λFLC levels were higher in stage III+IV and lymph node metastatic lung cancer patients compared to stage I+II and non-metastatic patients, with statistical significance (P=0.033 and P=0.019, respectively). The area under the curve (AUC) for κFLC and CEA in diagnosing lung cancer showed no significant difference (P=0.333). The combination of κFLC+CYFRA21-1 had the highest diagnostic efficacy (AUC=0.875) and sensitivity (71.3%). The AUC for the combined diagnosis of κFLC+λFLC+CEA+CYFRA21-1 was 0.915 (95% CI 0.860 to 0.953, P<0.001). CONCLUSIONS: Serum FLC is highly expressed in lung cancer and is associated with its invasion and metastasis. Serum FLC, particularly κFLC, has diagnostic value for lung cancer, and the combined detection of FLC, CEA, and CYFRA21-1 offers the best diagnostic efficacy.

Photothermal and Antibacterial PDA@Ag/SerMA Microneedles for Promoting Diabetic Wound Repair.

Diabetic foot ulcer (DFU) is a common and severe complication of diabetes characterized by wound neuropathy, ischemia, and susceptibility to infection, making its treatment difficult. Dressings are commonly used in treating diabetic wounds; however, they have disadvantages, including lack of flexibility and mechanical strength, lack of coagulation activity, resistance to biodegradation, and low drug delivery efficiency. Developing more effective strategies for diabetic wound treatment has become a new focus. Microneedles (MN) can be used as a drug delivery platform for DFU wounds, allowing safe, effective, painless and minimally invasive medication administration through the skin. Herein, PDA@Ag/SerMA microneedles were prepared by combining the photothermal properties of polydopamine (PDA), the antimicrobial properties of argentum (Ag), and the ability of sericin methacryloyl (SerMA) to promote cell mitosis to accelerate wound healing and treat diabetic ulcer wounds. The results revealed that PDA@Ag/SerMA microneedles exhibited approximately 100% antimicrobial efficacy against Staphylococcus aureus and Escherichia coli under 808 nm near-infrared (NIR) irradiation. Furthermore, the wound healing rate of mice reached 95% within 12 days, which demonstrated the excellent antibacterial properties and wound healing efficacy of PDA@Ag/SerMA microneedles at cellular and animal levels, providing a potential solution for treating DFU.

Quercetin inhibited LPS-induced cytokine storm by interacting with the AKT1-FoxO1 and Keap1-Nrf2 signaling pathway in macrophages.

Cytokine storm (CS) emerges as an exacerbated inflammatory response triggered by various factors such as pathogens and excessive immunotherapy, posing a significant threat to life if left unchecked. Quercetin, a monomer found in traditional Chinese medicine, exhibits notable anti-inflammatory and antiviral properties. This study endeavors to explore whether quercetin intervention could mitigate CS through a combination of network pharmacology analysis and experimental validation. First, common target genes and potential mechanisms affected by quercetin and CS were identified through network pharmacology, and molecular docking experiments confirmed quercetin and core targets. Subsequently, in vitro experiments of Raw264.7 cells stimulated by lipopolysaccharide (LPS) showed that quercetin could effectively inhibit the overexpression of pro-inflammatory mediators and regulate the AKT1-FoxO1 signaling pathway. At the same time, quercetin can reduce ROS through the Keap1-Nrf2 signaling pathway. In addition, in vivo studies of C57BL/6 mice injected with LPS further confirmed quercetin's inhibitory effect on CS. In conclusion, this investigation elucidated novel target genes and signaling pathways implicated in the therapeutic effects of quercetin on CS. Moreover, it provided compelling evidence supporting the efficacy of quercetin in reversing LPS-induced CS, primarily through the regulation of the AKT1-FoxO1 and Keap1-Nrf2 signaling pathways.

[Progress on external treatment of orthopaedics and traumatology by Mongolian medicine].

Mongolian medicine external treatment, which called five kinds of treatment in ancient time, is a kind of external treatment including fire moxibustion, poultice, soaking and other therapies. The therapy was gradually developed and perfected in the course of Mongolian people's long-term struggle against diseases, which has characteristics of small trauma and suitable for long-term application. In this paper, the research progress of external treatment of orthopedic diseases in Mongolian medicine in recent years was summarized, and it was concluded that external treatment of orthopedic diseases in Mongolian medicine had distinct characteristics and accurate efficacy. However, there are still deficiencies in the standardization of clinical operation and the study of the mechanism of therapeutic action, which need further research and improvement.

The Role and Underlying Mechanisms of Exercise in Heart Failure.

Heart failure is a prevalent and life-threatening syndrome characterized by structural and/or functional abnormalities of the heart. As a global burden with high rates of morbidity and mortality, there is growing recognition of the beneficial effects of exercise on physical fitness and cardiovascular health. A substantial body of evidence supports the notion that exercise can play a protective role in the development and progression of heart failure and improve cardiac function through various mechanisms, such as attenuating cardiac fibrosis, reducing inflammation, and regulating mitochondrial metabolism. Further investigation into the role and underlying mechanisms of exercise in heart failure may uncover novel therapeutic targets for the prevention and treatment of heart failure.

Abundant small microplastics hidden in water columns of the Yellow Sea and East China Sea: Distribution, transportation and potential risk.

Microplastics (MPs) pose significant concerns for marine ecological security due to their minuteness and ubiquity. However, comprehensive knowledge on their distribution and fate in seawater columns remains limited. This study investigated the abundances and characteristics of MPs across 3-6 water layers in the South Yellow Sea and East China Sea. Results indicate that high-abundance small MPs (< 100 µm) (average 6567 items/m3) were hidden beneath the sea-surface, predominantly fine-grained particles (< 20 µm) and high-density polymers (> 1.03 g/cm3). The total suspended MPs (5.0-834.2 µm) are estimated at 2.9-3.1 × 1017 particles, with most of them occurring in upper layers. In profiles, their distribution varied by physical properties with depth; fragment-shaped and high-density MPs increased in proportion at greater depths, contrasting with fibrous MPs. These MPs originated primarily from the Yangtze River and their winter transport was driven by the Yangtze River Dilution Water, East China Sea Coastal Current, and Yellow Sea Warm Current, resulting in their accumulation in coastal and estuarine regions. Consequently, the Yangtze River Estuary ecosystem faces substantial risks from MP pollution throughout the water column. This work unveils the prevalence of small MPs in coastal water columns and intricate interaction between their fate and hydrodynamic conditions.

Eco-friendly and highly efficient PM0.3 air filter made from nonwoven basalt fiber and electrospun nanocellulose fiber.

This study addresses the need for high-performance and sustainable air filters by developing a bio-based, high-efficiency particulate air (HEPA) filter. Current HEPA filters often rely on non-biodegradable materials, creating environmental burdens. In this paper, we presented a HEPA filter fabricated from natural basalt fiber (BF) and nanocellulose fiber. The developed filter featured a sandwich structure with electrospun nanocellulose fiber deposited onto a base BF layer, followed by a second BF layer and heat treatment. Various techniques were employed to characterize the obtained sample, and the results showed that the nonwoven BF fabric significantly reduced the pressure drop of the filter by up to 60 %. The nanocellulose fiber played a crucial role in achieving a remarkable filtration efficiency of 99.99 % for PM0.3. BF-based filter demonstrated exceptional fire resistance, hydrophobia, durability, and ease of cleaning, maintaining its effectiveness at temperatures up to 150 °C. Notably, it exhibited significantly better biodegradability than commercially available HEPA filters. By employing a hierarchical structure of sustainable basalt and cellulose fibers, this study paved the way for the development of next-generation hazardous particulate matter filters with exceptional performance in harsh conditions and reduced environmental impact.

Exploring the clinical and biological significance of the cell cycle-related gene CHMP4C in prostate cancer.

BACKGROUND: Prostate cancer (PCa) stands as the second most prevalent malignancy impacting male health, and the disease's evolutionary course presents formidable challenges in the context of patient treatment and prognostic management. Charged multivesicular body protein 4 C (CHMP4C) participates in the development of several cancers by regulating cell cycle functions. However, the role of CHMP4C in prostate cancer remains unclear. METHODS: In terms of bioinformatics, multiple PCa datasets were employed to scrutinize the expression of CHMP4C. Survival analysis coupled with a nomogram approach was employed to probe into the prognostic significance of CHMP4C. Gene set enrichment analysis (GSEA) was conducted to interrogate the functional implications of CHMP4C. In terms of cellular experimentation, the verification of RNA and protein expression levels was executed through the utilization of qRT-PCR and Western blotting. Upon the establishment of a cell line featuring stable CHMP4C knockdown, a battery of assays, including Cell Counting Kit-8 (CCK-8), wound healing, Transwell, and flow cytometry, were employed to discern the impact of CHMP4C on the proliferation, migration, invasion, and cell cycle function of PCa cells. RESULTS: The expression of CHMP4C exhibited upregulation in both PCa cells and tissues, and patients demonstrating elevated CHMP4C expression levels experienced a notably inferior prognosis. The nomogram, constructed using CHMP4C along with clinicopathological features, demonstrated a commendable capacity for prognostic prediction. CHMP4C knockdown significantly inhibited the proliferation, migration, and invasion of PCa cells (LNcaP and PC3). CHMP4C could impact the advancement of the PCa cell cycle, and its expression might be regulated by berberine. Divergent CHMP4C expression among PCa patients could induce alterations in immune cell infiltration and gene mutation frequency. CONCLUSIONS: Our findings suggest that CHMP4C might be a prognostic biomarker in PCa, potentially offering novel perspectives for the advancement of precision therapy for PCa.

[Genetic Variation of SH2B3 in Patients with Myeloid Neoplasms].

OBJECTIVE: To observe the genetic variation of SH2B3 in patients with myeloid neoplasms. METHODS: The results of targeted DNA sequencing associated with myeloid neoplasms in the Department of Hematology, Xuanwu Hospital, Capital Medical University from November 2017 to November 2022 were retrospectively analyzed, and the patients with SH2B3 gene mutations were identified. The demographic and clinical data of these patients were collected, and characteristics of SH2B3 gene mutation, co-mutated genes and their correlations with diseases were analyzed. RESULTS: The sequencing results were obtained from 1 005 patients, in which 19 patients were detected with SH2B3 gene mutation, including 18 missense mutations (94.74%), 1 nonsense mutation (5.26%), and 10 patients with co-mutated genes (52.63%). Variant allele frequency (VAF) ranged from 0.03 to 0.66. The highest frequency mutation was p.Ile568Thr (5/19, 26.32%), with an average VAF of 0.49, involving 1 case of MDS/MPN-RS (with SF3B1 mutation), 1 case of MDS-U (with SF3B1 mutation), 1 case of aplastic anemia with PNH clone (with PIGA and KMT2A mutations), 2 cases of MDS-MLD (1 case with SETBP1 mutation). The other mutations included p.Ala567Thr in 2 cases (10.53%), p.Arg566Trp, p.Glu533Lys, p.Met437Arg, p.Arg425Cys, p.Glu314Lys, p.Arg308*, p.Gln294Glu, p.Arg282Gln, p.Arg175Gln, p.Gly86Cys, p.His55Asn and p.Gln54Pro in 1 case each. CONCLUSION: A wide distribution of genetic mutation sites and low recurrence of SH2B3 is observed in myeloid neoplasms, among of them, p.Ile568Thr mutation is detected with a higher incidence and often coexists with characteristic mutations of other diseases.

Vertically Fluorinated Graphene Encapsulated SiOx Anode for Enhanced Li+ Transport and Interfacial Stability in High-Energy-Density Lithium Batteries.

Achieving high energy density has always been the goal of lithium-ion batteries (LIBs). SiOx has emerged as a compelling candidate for use as a negative electrode material due to its remarkable capacity. However, the huge volume expansion and the unstable electrode interface during (de)lithiation, hinder its further development. Herein, we report a facile strategy for the synthesis of surface fluorinated SiOx (SiOx@vG-F), and investigate their influences on battery performance. Systematic experiments investigations indicate that the reaction between Li+ and fluorine groups promotes the in-situ formation of stable LiF-rich solid electrolyte interface (SEI) on the surface of SiOx@vG-F anode, which effectively suppresses the pulverization of microsized SiOx particles during the charge and discharge cycle. As a result, the SiOx@vG-F enabled a higher capacity retention of 86.4% over 200 cycles at 1.0 C in the SiOx@vG-F||LiNi0.8Co0.1Mn0.1O2 full cell. This approach will provide insights for the advancement of alternative electrode materials in diverse energy conversion and storage systems.

Gastrointestinal problems in a valproic acid-induced rat model of autism: From maternal intestinal health to offspring intestinal function.

BACKGROUND: Autism spectrum disorder (ASD) is a developmental disorder characterized by social deficits and repetitive behavior. Gastrointestinal (GI) problems, such as constipation, diarrhea, and inflammatory bowel disease, commonly occur in patients with ASD. Previously, GI problems of ASD patients were attributed to intestinal inflammation and vertical mother-to-infant microbiome transmission. AIM: To explore whether GI problems in ASD are related to maternal intestinal inflammation and gut microbiota abnormalities. METHODS: An ASD rat model was developed using valproic acid (VPA). Enzyme-linked immunosorbent assay and fecal 16S rRNA sequencing were used to test GI changes. RESULTS: VPA exposure during pregnancy led to pathological maternal intestinal changes, resulting in alterations in maternal gut microbiota. Additionally, the levels of inflammatory factors also increased. Moreover, prenatal exposure to VPA resulted in impaired duodenal motility in the offspring as well as increased levels of inflammatory factors. CONCLUSION: GI problems in ASD may be associated with maternal intestinal inflammation and microbiota abnormality. Future research is required to find more evidence on the etiology and treatment of GI problems in ASD.

How health seeking behavior develops in patients with type 2 diabetes: a qualitative study based on health belief model in China.

Background: Type 2 diabetes(T2DM) is a global health problem which is accompanied with multi-systemic complications, and associated with long-term health burden and economic burden. Effective health seeking behavior (HSB) refers to reasonably utilize health resources, effectively prevent and treat diseases, and maintain health. Effective health seeking behavior (HSB) is vital to mitigate the risk of T2DM complications. However, health seeking behavior for T2DM patients remains sub-optimal worldwide. Objective: The study aimed to explore the internal logic of how health seeking behavior of T2DM patients develops and the influencing factors of health seeking behavior. With a view to provide a reference basis for improving the health seeking behavior situation of T2DM patients. Methods: This study was conducted at an integrated tertiary hospital in China. People who were diagnosed with T2DM, capable of expressing clearly and had no mental illness, were approached based on a purposive sampling. The experience of T2DM and health seeking behavior were collected via in-depth interviews. A theory-driven thematic analysis based on Health Belief Model (HBM) was applied for data analysis. Inductive reasoning was used to identify emerging themes which were not included in HBM. Results: 26 patients with T2DM were included in the current study. Seven themes were identified, including: (1) T2DM diagnosis and severity; (2) T2DM treatment and management; (3) Perceived susceptibility of diabetes progression; (4) Perceived severity of diabetes progression; (5) Perceived benefits of health seeking behavior; (6) Perceived barriers of health seeking behavior; (7) Perception of behavioral cues. Generally, patients with T2DM lacked reliable sources of information, considered T2DM to be slow-progressing and without posing an immediate threat to life. Consequently, they did not fully grasp the long-term risks associated with T2DM or the protective effects of health seeking behavior. Conclusion: This study highlighted the challenges in health seeking behavior for patients with T2DM. It suggested that future interventions and strategies should involve multi-faceted approaches, targeting healthcare providers (HCPs), patients with T2DM, and their support networks. This comprehensive strategy can help patients better understand their condition and the importance of effective health seeking behavior. Ultimately, enhancing their capacity for adopting appropriate health-seeking practices.

Mechanisms and clinical landscape of N6-methyladenosine (m6A) RNA modification in gastrointestinal tract cancers.

Epigenetics encompasses reversible and heritable chemical modifications of non-nuclear DNA sequences, including DNA and RNA methylation, histone modifications, non-coding RNA modifications, and chromatin rearrangements. In addition to well-studied DNA and histone methylation, RNA methylation has emerged as a hot topic in biological sciences over the past decade. N6-methyladenosine (m6A) is the most common and abundant modification in eukaryotic mRNA, affecting all RNA stages, including transcription, translation, and degradation. Advances in high-throughput sequencing technologies made it feasible to identify the chemical basis and biological functions of m6A RNA. Dysregulation of m6A levels and associated modifying proteins can both inhibit and promote cancer, highlighting the importance of the tumor microenvironment in diverse biological processes. Gastrointestinal tract cancers, including gastric, colorectal, and pancreatic cancers, are among the most common and deadly malignancies in humans. Growing evidence suggests a close association between m6A levels and the progression of gastrointestinal tumors. Global m6A modification levels are substantially modified in gastrointestinal tumor tissues and cell lines compared to healthy tissues and cells, possibly influencing various biological behaviors such as tumor cell proliferation, invasion, metastasis, and drug resistance. Exploring the diagnostic and therapeutic potential of m6A-related proteins is critical from a clinical standpoint. Developing more specific and effective m6A modulators offers new options for treating these tumors and deeper insights into gastrointestinal tract cancers.

Palladium-Catalyzed O-Glycosylation through π-π Interactions.

A stereodivergent synthesis of ß- and α-O-glycosides using 3-O-quinaldoyl glucals was developed by palladium catalysis at 60 and 110 °C respectively. Various alcohols, monosaccharides, and amino acid were glycosylated to form ß- and α- products in good yields with high stereoselectivity. Mechanistic studies indicated no classic Pd-N (quinoline) coordination, but π-π stacking interactions promoted the anomeric stereodiversity. The practicality was demonstrated by glycosylating natural products/drugs and synthesizing a complex tetrasaccharide.

Robust k -Means-Type Clustering for Noisy Data.

Data clustering is a fundamental machine learning task that seeks to categorize a dataset into homogeneous groups. However, real data usually contain noise, which poses significant challenges to clustering algorithms. In this article, motivated by how the k -means algorithm is derived from a Gaussian mixture model (GMM), we propose a robust k -means-type algorithm, named k -means-type clustering based on t -distribution (KMTD), by assuming that the data points are drawn from a special multivariate t -mixture model (TMM). Compared to the Gaussian distribution, the t -distribution has a fatter tail. The proposed algorithm is more robust to noise. Like the k -means algorithm, the proposed algorithm is simpler than those based on a full TMM. Both synthetic and actual data are used to illustrate the proposed algorithm's performance and efficiency. The experimental results demonstrated that the proposed algorithm operates more quickly than other sophisticated algorithms and, in most cases, achieves higher accuracy than the other algorithms.