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Abstract Crohn’s disease (CD) is a chronic inflammatory autoimmune disease of unknown etiology. To identify new targets related to the initiation of CD, we screened a pair of twins with CD, which is a rare phenomenon in the Chinese population, for genetic susceptibility factors. Whole-exome sequencing (WES) of these patients revealed a mutation in their SERPINB4 gene. Therefore, we studied a wider clinical cohort of patients with CD or ulcerous colitis (UC), healthy individuals, and those with a family history of CD for this mutation by Sanger sequencing. The single-nucleotide difference in the SERPINB4 gene, which was unique to the twin patients with CD, led to the substitution of lysine by a glutamic acid residue. Functional analysis indicated that this mutation of SERPINB4 inhibited the proliferation, colony formation, wound healing, and migration of intestinal epithelial cells (IECs). Furthermore, mutation of SERPINB4 induced apoptosis and activated apoptosis-related proteins in IECs, and a caspase inhibitor significantly reduced these effects. Transcriptome sequencing revealed that the expression of genes encoding proinflammatory proteins (IL1B, IL6, IL17, IL24, CCL2, and CXCR2) and key proteins in the immune response (S100A9, MMP3, and MYC) was significantly upregulated during SERPINB4 mutant-induced apoptosis. Thus, the heterozygous SERPINB4 gene mutation causes the dysfunction of IECs, which would disrupt the intestinal epithelial barrier and contribute to the development of intestinal inflammation. The activation of SERPINB4 might represent a novel therapeutic target for inflammatory bowel disease.

Abstract Pinctada fucata martensii (P. f. martensii) is one of the main pearl oysters cultured in artificial seawater in China. However, it is highly susceptible to pathogen infection under intensive cultivation near the coast. MicroRNAs (miRNAs), as an innovative and potent regulator of immune function, play a pivotal role in the immune response of pearl oysters to external stimuli and are a potent marker for the response of P. f. martensii to infection. This study identified two novel miRNAs, novel-13 and novel-44, from the whole transcriptome of the P. f. martensii hemocyte before and after infection with Vibrio parahaemolyticus. The dual luciferase results showed that novel-13 negatively regulated LAAO and novel-44 negatively regulated ILK. The activity of antioxidant-related enzymes increased significantly in the synthetic miRNA (novel-13 and novel-44) inhibitors and decreased significantly in the synthetic miRNA mimics. In the challenge experiment, injection with miRNA inhibitor increased the relative survival percentage by 10% compared with the control group. In conclusion, the overexpression of novel-13 and novel-44 can decrease the activity of immune and antioxidant-related enzymes, possibly affecting immune regulation in P. f. martensii by negatively regulating the LAAO and ILK target genes.

Abstract Background As the common antibacterial drugs in folic acid oral liquid, parabens are listed as mandatory substances in the quality standard. Both the Chinese Pharmacopoeia and the United States Pharmacopoeia use high performance liquid chromatography for the determination of folic acid, but the quantitative methods of parabens are different. Pharmacopoeias use different instruments to quantify folic acid and parabens, resulting in cumbersome and cumbersome detection methods. Objective Without changing the type of instrument and mobile phase, two methods were established for the determination of folic acid and parabens (methyl paraben; ethyl paraben; propyl paraben) using respective wavelengths and flow comparisons Propyl benzoate) high performance liquid chromatography method. Method Chromatographic separation was achieved on an Agilent 5 TC-C18 HPLC column (5 μm; 250 μm × 4.6 mm) maintained at 25 °C (column temperature). The mobile phase consisted of phosphate buffer (pH 4.0)-methanol. When the ratio is 99:1, it is used to determine the content of folic acid, and when the ratio is 79:21, it is used to determine the content of antimicrobial agents. The flow rate used was 1.2 mL/min, the injection volume of folic acid was 20 µL, and the injection volume of bacteriostatic agent was 50 µL. In addition, the blue applicability grade index (BAGI) and analytical greenness (AGREE) metric tools were used to evaluate the greenness and environmental friendliness of the developed methods. Results The method has a good linear relationship with R2 ≥ 0.9995, the average recovery rate of the two methods is ≥ 95%, and the relative standard deviation (RSD%) accuracy is less than 0.21%. The BAGI tool characterizes the developed method as green. The AGREE score is around 0.5, and the method is also largely consistent with the principles of green analytical chemistry. Conclusions The HPLC method was established for the rapid determination of folic acid and antibacterial agent of parabens in folic acid. The method has high accuracy, strong specificity, high recovery rate, good stability and environmental friendliness. Compared with the method in the pharmacopoeia, it has strong resistance to complex matrix interference, greatly shortens the detection time, and has little damage to the instrument and chromatographic column. It can be used for the quality standard of folic acid oral liquid.

Abstract Background Invasive pulmonary aspergillosis (IPA) is a common opportunistic infection in patients with severe liver disease (SLD), which increases the mortality of patients. The aim of this study was to evaluate the efficacy and safety of voriconazole for IPA in patients with SLD and explore an optimal antifungal regimen. Methods This was a retrospective cohort study of SLD patients diagnosed with proven or probable IPA at Beijing Youan Hospital, Capital Medical University between January 1, 2012 to January 31, 2023. Univariate and multivariate logistic regression analysis were performed to identify the impact of voriconazole on outcomes of SLD patients with IPA. Results A total of 142 patients were enrolled and categorized into voriconazole group (n = 92), echinocandins group (n = 26) and a combination of voriconazole and echinocandins group (n = 24). The 28-day all-cause mortality was lower in voriconazole group compared to the other groups (p = 0.033). Voriconazole monotherapy was associated with lower short-term mortality (OR 0.223, 95%CI 0.070–0.650, p = 0.008) and did not seem to exacerbate hepatic function deterioration in SLD patients with IPA (OR 0.259, 95%CI 0.094–0.674, p = 0.007) when compared to echinocandins monotherapy. Among the three subgroups of voriconazole monotherapy, no-loading dose regime demonstrated a superior response to IPA therapy compared to the standard-dose regimen (OR 0.264, 95%CI 0.068–0.845, p = 0.035). Conclusion Voriconazole monotherapy demonstrated good tolerability with lower mortality in SLD patients with IPA. A no-loading dose voriconazole regimen is proposed for IPA treatment in SLD patients, yet pharmacokinetic studies combined with prospective studies are needed for further validation.

Abstract Background Alzheimer’s disease (AD) is a complex neurodegenerative disorder with a largely unexplored epigenetic landscape. Objective This study employs an innovative approach that integrates multi-omics analysis and explainable machine learning to explore the epigenetic regulatory mechanisms underlying the epigenetic signature of PRRT1 implicated in AD. Methods Through comprehensive DNA methylation and transcriptomic profiling, we identified distinct epigenetic signatures associated with gene PRRT1 expression in AD patient samples compared to healthy controls. Utilizing interpretable machine learning models and ELMAR analysis, we dissected the complex relationships between these epigenetic signatures and gene expression patterns, revealing novel regulatory elements and pathways. Finally, the epigenetic mechanisms of these genes were investigated experimentally. Results This study identified ten epigenetic signatures, constructed an interpretable AD diagnostic model, and utilized various bioinformatics methods to create an epigenomic map. Subsequently, the ELMAR R package was used to integrate multi-omics data and identify the upstream transcription factor MAZ for PRRT1. Finally, experiments confirmed the interaction between MAZ and PRRT1, which mediated apoptosis and autophagy in AD. Conclusion This study adopts a strategy that integrates bioinformatics analysis with molecular experiments, providing new insights into the epigenetic regulatory mechanisms of PRRT1 in AD and demonstrating the importance of explainable machine learning in elucidating complex disease mechanisms.

Abstract Bacterial pneumonia is a significant public health burden, contributing to substantial morbidity, mortality, and healthcare costs. Current therapeutic strategies beyond antibiotics and adjuvant therapies are limited, highlighting the need for a deeper understanding of the disease pathogenesis. Here, we employed single-cell RNA sequencing of 444,146 bronchoalveolar lavage fluid cells (BALFs) from a large cohort of 74 individuals, including 58 patients with mild (n = 22) and severe (n = 36) diseases as well as 16 healthy donors. Enzyme‐linked immunosorbent and histological assays were applied for validation within this cohort. The heterogeneity of immune responses in bacterial pneumonia was observed, with distinct immune cell profiles related to disease severity. Severe bacterial pneumonia was marked by an inflammatory cytokine storm resulting from systemic upregulation of S100A8/A9 and CXCL8, primarily due to specific macrophage and neutrophil subsets. In contrast, mild bacterial pneumonia exhibits an effective humoral immune response characterized by the expansion of T follicular helper and T helper 2 cells, facilitating B cell activation and antibody production. Although both disease groups display T cell exhaustion, mild cases maintained robust cytotoxic CD8+T cell function, potentially reflecting a compensatory mechanism. Dysregulated neutrophil and macrophage responses contributed significantly to the pathogenesis of severe disease. Immature neutrophils promote excessive inflammation and suppress T cell activation, while a specific macrophage subset (Macro_03_M1) displaying features akin to myeloid-derived suppressor cells (M-MDSCs) suppress T cells and promote inflammation. Together, these findings highlight potential therapeutic targets for modulating immune responses and improving clinical outcomes in bacterial pneumonia.

Abstract Lung diseases often coincide with imbalances in gut microbiota, but the role of gut microbiota in pulmonary fibrosis (PF) remains unclear. This study investigates the impact of gut microbiota and their metabolites on PF. Serum and lung tissues of normal, bleomycin (BLM)- and silica-induced mice showed significant differences in gut microbiota. l-Tryptophan was upregulated within pulmonary tissue and serum metabolites both in the BLM and Silica groups. The dominant gut microbiota associated with l-tryptophan metabolism included Lachnospiraceae_NK4A136_Group, Allobaculum, Alistipes, and Candidatus_Saccharimonas. l-Tryptophan promoted BLM- and silica-induced pathological damage in PF mice. l-Tryptophan promoted TGF-β1-induced EMT and fibroblast activation in vitro via activating the mTOR/S6 pathway. In conclusion, PF mice exhibited alterations in gut microbiota and serum and lung tissue metabolites. l-Tryptophan level was associated with changes in gut microbiota, and l-tryptophan promoted PF progression in both in vivo and in vitro models, potentially through activation of the mTOR/S6 pathway.

Abstract This study offers a comprehensive analysis of the Perturbed Schrödinger -Hirota Equation (PSHE), crucial for understanding soliton dynamics in modern optical communication systems. We extended the traditional Nonlinear Schrödinger Equation (NLSE) to include higher-order nonlinearities and spatiotemporal dispersion, capturing the complexities of light pulse propagation. Employing the modified auxiliary equation method and Adomian Decomposition Method (ADM), we derived a spectrum of exact traveling wave solutions, encompassing exponential, rational, trigonometric, and hyperbolic functions. These solutions provide insights into soliton behaviors across diverse parameters, essential for optimizing fiber optic systems. The precision of our analytical solutions was validated through numerical solutions, and we explored modulation instability, revealing conditions for soliton formation and evolution. The findings have significant implications for the design and optimization of next-generation optical communication technologies.

Abstract Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by limited effective treatments, underscoring the critical need for early detection and diagnosis to improve intervention outcomes. This study integrates various bioinformatics methodologies with interpretable machine learning to identify reliable biomarkers for AD diagnosis and treatment. By leveraging differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis (WGCNA), and construction of Protein-Protein Interaction (PPI) Networks, we meticulously analyzed the AD dataset from the GEO database to pinpoint Hub genes. Subsequently, various machine learning algorithms were employed to construct diagnostic models, which were then elucidated using SHapley Additive exPlanations (SHAP). To visualize our findings, we generated an insightful bioinformatics map of 10 Hub genes. We then conducted experimental validation on less-studied Hub genes, revealing significant differential mRNA expression of MYH9 and RHOQ in an AD cell model. Finally, we explored the biological significance of these two genes at the single-cell transcriptome level. This study not only introduces interactive SHAP panels for precise decision-making in AD but also offers novel insights into the identification of AD biomarkers through interpretable machine learning diagnostic models. Particularly, MYH9 has emerged as a promising new potential biomarker, pointing the way towards enhanced diagnostic accuracy and personalized therapeutic strategies for AD. Although the mRNA expression patterns of RHOQ are opposite in AD cell models and human brain tissue samples, the role of RHOQ in AD remains worthy of further exploration due to the diversity and complexity of biological molecular regulation.

This study aimed to evaluate the characteristic aroma compounds of white tea made from ‘Fuhuang 1’, an albino mutant of ‘Fuandabaicha’, and their dynamic changes during tea processing. The types and relative contents of volatile compounds in ‘Fuhuang 1’ and ‘Fuandabaicha’ tea leaves withered for 0, 12, 24, 36 and 48 h and in white tea made from each variety were determined by headspace solid-phase microextraction combined with gas chromatography-mass spectrometry (HS-SPME-GC-MS). A total of 560 aroma compounds were detected in all samples, among which terpenes, heterocyclic compounds, esters and hydrocarbons were the major aroma components of white tea. During the withering process, the total content of volatile metabolite in both cultivars gradually increased, reaching the highest value at 48 h. Based on their relative odor activity values (ROAVs), terpinolene, citral, 1-octen-3-one, and damascenone were identified as the key aroma components of ‘Fuandabaicha’ white tea, and these compounds together with methyl salicylate and benzaldehyde as the key aroma components of ‘Fuhuang 1’ white tea. 1-Octen-3-one and citral were accumulated in large amounts at the early stage of withering and then decreased. Terpenolene, benzaldehyde, methyl salicylate, and damascus ketone continuously increased during the whole withering process. Terpinolene, citral, 1-octen-3-one, and damascenone greatly contributed to the floral, fruity and sweet aroma of ‘Fuhuang 1’ and ‘Fuandabaicha’ white tea. 1-Octene-3-one, methyl salicylate, and benzaldehyde were the key compounds responsible for the clean and fresh aroma of ‘Fuhuang 1’ white tea. This study helps gain insights into the aroma characteristics of ‘Fuhuang 1’ white tea and provides a scientific basis for the research and development of white tea made from albino tea plant mutants.

Abstract Background Healthcare fragmentation and lack of care coordination are longstanding problems in cancer care. This study’s goal was to provide in-depth understanding of how the organization and fragmentation of healthcare impacts the experiences of patients with advanced cancer and their families, especially near the end-of-life. Methods This mixed-methods quality improvement study took place at a large multi-specialty healthcare organization in Northern California. Electronic health record data was used to identify patients with advanced cancer and their characteristics. Data were collected 10/2019-05/2022 through periodic patient surveys and in-depth interviews with sampled family members, including open-ended questions about overall healthcare experiences. Data were analyzed using inductive thematic analysis. Results Overall, 281/482 (58.3%) patients with advanced cancer completed surveys. Surveyed patients’ mean age was 68 (SD: 12.8) years, 53% were male, 73% White, 14.2% Asian, 1.4% Black, 3.9% Other; 8.9% Hispanic, and 19.2% were deceased within 12 months. Twenty-four family members completed in-depth interviews: 17/24 (70.8%) were spouses, 62.5% were female and 50% were interviewed after the patient’s death. Respondents were generally positive about health care team interactions, but consistently brought up the negative impacts of the organization of healthcare, “It is not the fault of the health care team - it is the way the system works.” Three major challenges were identified. (1) Systemic healthcare care fragmentation, including difficulties navigating care across providers and institutions, “It seems like everything is like an isolated incident… there’s no overall, big picture viewpoint.” (2) Administrative burdens, “In the end I gave up [scheduling care] because I was tired of calling.” (3) Financial burdens, “This oncologist wanted to put him on a drug…but it was $4000 a month.” Respondents described these challenges leading to worse quality of care, health, and quality of life, and loss of trust in the national healthcare system. Conclusions These findings illustrate how care fragmentation and administrative and financial burdens lead to worse quality care and distrust of healthcare. Better coordination of patient-centered care, and a fundamental restructuring of a highly fragmented national healthcare system are required to meet the needs of patients with complex conditions like advanced cancer and their families.

Abstract Charge stripes have been widely observed in many different types of unconventional superconductors, holding varying periods ( $${{\mathcal{P}}}$$ P ) and intensities. However, a general understanding on the interplay between charge stripes and superconducting properties is still incomplete. Here, using large-scale unbiased numerical simulations on a general inhomogeneous Hubbard model, we discover that the charge-stripe period $${{\mathcal{P}}}$$ P , which is variable in different real material systems, could dictate the pairing symmetries—d wave for $${{\mathcal{P}}}\ge 4,s$$ P ≥ 4 , s and d waves for $${{\mathcal{P}}}\le 3$$ P ≤ 3 . In the latter, tuning hole doping and charge-stripe amplitude can trigger a d-s wave transition and magnetic-correlation shift, where the d-wave state converts to a pairing-density wave state, competing with the s wave. These interesting phenomena arise from an unusual stripe-induced selection rule of pairing symmetries around on-stripe region and within inter-stripe region, giving rise to a critical point of $${{\mathcal{P}}}=3$$ P = 3 for the phase transition. In general, our findings offer important insights into the differences in the superconducting pairing mechanisms across many $${{\mathcal{P}}}$$ P -dependent superconducting systems, highlighting the decisive role of charge stripe.

Background: Senile osteoporosis (SOP) is a systemic bone disease characterized by increased susceptibility to fractures. However, there is currently no effective treatment for SOP. The Zhuangyao Jianshen Wan (ZYJSW) pill is traditionally believed to possess kidney-nourishing and bone-strengthening effects, demonstrating efficacy in treating fractures. Despite this, its effectiveness and mechanism in SOP remain unclear. This study aims to investigate the therapeutic potential of ZYJSW in treating SOP in senescence accelerated mouse prone 6 (SAMP6, P6) mice, and elucidate the underlying mechanisms. Methods: Four-month-old SAMP6 mice were categorized into six groups: the model group (SAMP6), low, medium, and high-dose ZYJSW treatment groups, calcitriol treatment (positive control 1) group, and metformin treatment (positive control 2) group. Gastric administration was carried out for 15 weeks, and a normal control group comprising four-month-old Senescence-Accelerated Mouse Resistant 1 (SAMR1) mice. Changes in body weight, liver and kidney function, bone protective effects, and muscle quality were evaluated using various assays, including H&E staining, Goldner staining, bone tissue morphology analysis, Micro-CT imaging, and biomechanical testing. Qualitative analysis and quality control of ZYJSW were performed via LC-MS/MS analysis. To explore mechanisms, network pharmacology and proteomics were employed, and the identified proteins were validated by Western blotting. Results: Oral administration of ZYJSW to P6 mice exerted preventive efficacy against osteopenia, impaired bone microstructure, and poor bone and muscle quality. ZYJSW attenuated the imbalance in bone metabolism by promoting bone formation, as evidenced by the upregulation of key factors such as Runt-related transcription factor 2 (RUNX2), Bone Morphogenetic Protein (BMP2), Osteoprotegerin (OPG) and Osteocalcin (OCN), while simultaneously inhibiting bone resorption through the downregulation of TNF receptor associated factor 6 (TRAF6), Tartrate resistant acid phosphatase (TRAP), Receptor activator for nuclear factor-κB ligand (RANKL) and Cathepsin K (CTSK). Additionally, ZYJSW enhanced muscle structure and function by counteracting the elevation of Ubiquitin (Ub), Muscle RING-finger protein-1 (Murf-1), F-Box Protein 32 (FBOX32), and Myogenin (Myog). Network pharmacology predictions, proteomics analysis corroborated by published literature demonstrated the role of ZYJSW involving in safeguarding mitochondrial biogenesis. This was achieved by suppressing GCN5L1 expression, contributing to the heightened expression of TFAM, PGC-1α, and nuclear respiratory factor-1 (NRF-1) proteins. ZYJSW also positively modulated Wnt signaling pathways responsible for bone formation, due to regulating expressions of key components like β-catenin, GSK-3β, and LRP5. In addition, ZYJSW causes the downregulation of the PI3K/Akt pathway by inhibiting the phosphorylation of both PI3K and Akt. Conclusions: The study highlights the significance of ZYJSW in preserving the health of both bone and muscle in P6 mice, potentially through the regulation of the GCN5L1-mediated PI3K/Akt/Wnt signaling pathway. The translational potential of this article: Our research provides evidence and a mechanistic rationale for ZYJSW as a candidate for SOP treatment, offering insights for further exploration and strategy development.

To screen and identify high chitosanase producing strains and to optimize the fermentation condition and analyze the enzymatic properties of the target strain. In this study, high chitosanase-producing strain was screened from the sediment of shrimp ponds in Beihai, Guangxi through primary and secondary screening. The strain underwent identification, the enzyme production process of the strain was optimized through single-factor, Plackett-Burman and orthogonal optimization methods. The enzymatic properties and products of chitosanase produced by the strain were studied. The results showed that the strain of Gxun-5.3.3 with high chitosanase production was obtained by screening and was identified as Bacillus cereus. The optimal components for the enzyme-producing medium of B. cereus Gxun-5.3.3 was maltose 5 g/L, yeast powder 3 g/L, chitosan 15 g/L, and the initial pH and fermentation time were 6.0 and 84 h, respectively. Under the optimized conditions, the chitosanase activity reached 62.03±1.18 U/mL, which was 55.58% higher before optimization (39.87±1.24 U/mL). The protease produced by strain Gxun-5.3.3 had maximum activity at 60 ℃ and optimum pH at 5.0, respectively. Metal ions Fe2+ and Mn2+ had a significant (P

Abstract Background SARS-CoV-2 viremia is associated with disease severity and high risk for in-hospital mortality. However, the impact of SARS-CoV-2 viremia on long-term outcomes in hospitalized patients with COVID-19 is poorly understood. Methods We conducted a prospective cohort study and recruited a group of older adult patients with COVID-19 admitted to pulmonary intermediate care units of Peking University Third Hospital during December 2022 and January 2023. The plasma level of SARS-CoV-2 RNA was determined by a standardized RT-PCR technique, and SARS-CoV-2 RNAemia was defined as a plasma viral load ≥ 50 copies/ml. In-hospital and follow-up (180-day) outcome data were collected. Results A total of 101 patients with an average of 80.4 years were recruited, and 63.4% of them were severe or very severe cases. Twenty-eight patients (27.7%) had SARS-CoV-2 RNAemia, with a median viral RNA load of 422.1 [261.3, 1085.6] copies/ml. Patients with SARS-CoV-2 RNAemia were more likely to develop critical cases and had a higher incidence of sepsis. Accordingly, they had a higher 180-day mortality (57.1% vs. 19.7%, P

Abstract Two-dimensional (2D) multiferroic materials are recognized as promising candidates for next-generation nanodevices due to their tunable magnetoelectric coupling and distinctive physical phenomena. In this study, we proposed a novel 2D multiferroic van der Waals heterostructure (vdWH) by stacking atomic layers of ferroelectric In2Se3 and ferromagnetic MnI3. Using first-principles calculations, we found that the MnI3/In2Se3 vdWH exhibit robust metallic conductivity across various spin and polarization states, preserving the distinctive band characteristics of isolated In2Se3 and MnI3. However, the alignment of Fermi levels causes the conduction band minimum (CBM) and valence band maximum (VBM) of In2Se3 and MnI3 to shift relative to their original band structures. Remarkably, the MnI3/In2Se3 with the upward polarization state of In2Se3 exhibits an Ohmic contact. Switching the polarization direction of In2Se3 from upward to downward can transform the MnI3/In2Se3 vdWH from an Ohmic contact to a p-type Schottky contact, while also modifying its dipole moment, magnetic strength and direction. Based on these properties of MnI3/In2Se3 vdWH, we designed the field-effect transistors (FETs) with high on/off rates and nonvolatile data storage device. Furthermore, the Schottky barrier heights (SBHs), magnetic moment, and dipole moment of MnI3/In2Se3 vdWH can also be effectively regulated by reducing the interlayer distance. With the continuous reduction of the interlayer distance of MnI3/In2Se3 vdWH, its easy magnetization axis is expected to shift from in-plane to out-of-plane. These findings offer new insights for the design and development of the next-generation spintronic and nonvolatile memory nanodevices.

Abstract Magnesium (Mg) plays a pivotal role as an essential component of plant chlorophyll and functions as a critical coenzyme. However, research exploring the regulatory mechanisms of magnesium ions on the synthesis of secondary metabolites is still in its early stages. Sophora tonkinensis is a widely utilized medicinal plant in China, recognized for its diverse secondary metabolites with active properties. This study investigates variations in these ingredients in tissue-cultured seedlings under varying magnesium concentrations. Simultaneously, an omics data analysis was conducted on tissue-cultured seedlings subjected to treatments with magnesium and low magnesium. These comprehensive omics analyses aimed to elucidate the mechanisms through which magnesium influences active components, growth, and development. Magnesium exerts a pervasive influence on various metabolic pathways, forming an intricate network. Research findings indicate that magnesium impacts diverse metabolic processes, including the absorption of potassium and calcium, as well as photosynthetic activity. Consequently, these influences lead to discernible changes in the levels of pharmacologically active compounds and the growth and developmental status.This study is the first to employ a multi-omics data analysis in S. tonkinensis. This methodology allows us to uncover the overarching impact of metabolic networks on the levels of various active ingredients and specific phenotypes.

Abstract High-grade B-cell lymphoma with 11q aberration (HGBL-11q) is a distinct lymphoma entity according to the 5th edition of the WHO classification of hematolymphoid tumors. It lacks MYC translocation but carries proximal gains and/or telomeric losses of chromosome 11q. This rare type of B-cell lymphoma is less frequently reported in people living with HIV (PLWH), and its exact frequency remains unclear. Our goal was to retrospectively analyze its frequency in a cohort of aggressive B-cell lymphomas in PLWH, including Burkitt lymphoma (BL, n = 35), diffuse large B-cell lymphoma (DLBCL, n = 48), high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS, n = 13), which was diagnosed as AIDS-related lymphoma (ARL) at our institution. In total, 10/96 (10.4%) cases harbored the typical 11q aberration pattern, predominantly those that had been classified as BL (6/35, 17.1%), DLBCL (2/48, 4.2%), and HGBL, NOS (2/13, 15.4%). We also evaluated 7 cases of AIDS-related HGBL-11q (AR-HGBL-11q) reported in the literature. The median age of our cohort was 35 years, and all the patients were male. Most cases (70%) had a history of HIV infection for over 1 year, and all were involved in lymph nodes (100%), frequently involved extranodal sites (60%), and Ann Arbor stage III/IV. In histomorphology, the cases exhibited diverse cytological features, reminiscent of BL (6 cases), DLBCL (2 cases), and HGBL (2 cases). A comparison of the combined cohort of 17 AR-HGBL-11q cases with 11 ARL cases that lacked both MYC rearrangement and 11q aberration at our institution showed that HGBL-11q cases were characterized by strikingly coarse apoptotic debris (P

Yellow nail syndrome (YNS) is a rare clinical syndrome characterized by nail bed changes, pulmonary involvement, and lymphatic drainage disorders. Pulmonary involvement usually manifests as bronchiectasis, bronchiolitis, and pleural effusion. There are few studies on yellow nail syndrome combined with opportunistic infection. Here, we report a case of clinically diagnosed YNS combined with Nocardia cyriacigeorgica infection and the course of treatment used, which can provide some useful information for clinicians to better understand this rare illness.

Parenting style plays an important role in children's externalizing behaviors. Differences in physiological regulation among children may lead to variations in whether or to what extent parenting style influences them. The present study aimed to investigate the effect of parenting styles on young children's development of externalizing behaviors and to consider the moderating role of children's physiological regulation (resting respiratory sinus arrhythmia [resting RSA]). Participants included 119 Chinese parent-child dyads (55 girls, T1 M[subscript age] = 4.62 years, SD[subscript age] = 0.27 years; T2 M[subscript age] = 5.73 years, SD[subscript age] = 0.29 years). At T1, parents reported their parenting styles and children's externalizing behaviors; at T2, children's externalizing behaviors were measured again by parental reports, and children's resting RSA was measured. Authoritarian parenting predicted children's development of externalizing behaviors from T1 to T2, and this effect was moderated by children's resting RSA. For children with low resting RSA, authoritarian parenting positively predicted their development of externalizing behaviors, but no significant relation was found among children with high resting RSA. Permissive parenting was associated with children's externalizing behaviors T1 but not with the development of externalizing behaviors from T1 to T2. The present study demonstrates the crucial role of resting RSA in early childhood and supports the diathesis-stress model by revealing that children with poor physiological regulation are vulnerable to authoritarian parenting and thus develop high externalizing behaviors.

While telegenetic counseling has increased substantially since the start of the COVID-19 pandemic, previous studies reported concerns around building rapport, nonverbal communication, and the patient-counselor relationship. This qualitative evaluation elicited feedback from genetic counselors, referring clinicians, and patients from a single healthcare organization to understand the user-driven reasons for overall satisfaction and experience. We conducted 22 in-depth, semi-structured interviews with participants from all 3 groups between February 2022 and February 2023. Interview recordings were transcribed and analyzed using a pragmatic thematic approach. Participants across all groups felt the style and content of the genetic counseling visit lent itself perfectly to telegenetics specifically because of no physical exam component. Most patient and counselor participants expressed having the genetic counseling over phone or video had no impact on the patient-counselor relationship or the amount of trust and emotional connection they were able to achieve remotely. Preference for visit type can be influenced by in-person masking requirements impeding full facial expressions or expressing strong emotions over phone. All respondents expressed strong support for all modalities going forward. Counselors with broad experience across platforms should be the focus of future recruitment as should patient education around the nature of the genetic counseling visit and the accuracy of various testing options. Telegenetic programs should consider perspectives from all 3 groups to ensure that specific needs of each are addressed.

This study sought to investigate the thermal stability and digestibility of corn starch sugar residue resistant starch (CSSR-RS) through comparative analysis of the physicochemical properties and structural characteristics among CSSR-RS, high-amylose corn starch (HS), and normal corn starch (NS). CSSR-RS contained 51.76 % resistant starch (RS), with 42.6 % remaining after high-temperature treatment, which was significantly higher than HS, demonstrating strong resistance to gelatinization. CSSR-RS is characterized by highly ordered aggregation of small molecules with a C-type crystalline structure, and irregular granular structures with wrinkled surfaces. Compared with NS and HS, the short-range and long-range order of CSSR-RS were significantly higher, indicating excellent thermal stability. In vitro simulated digestion revealed that the total hydrolysis rate of CSSR-RS was significantly lower than those of NS and HS, and the residual digesta of CSSR-RS also showed better resistance to digestion than HS. CSSR-RS exhibited significant development prospects in healthy food.

Water stemming is an efficient method of removing blasting dust by wetting. There is still a lack of methods for rapid optimization of water stemming components with high wettability. Herein, blasting dust was collected from a tunnel in Chongqing (China) to investigate its removal performance by different water stemmings. The two most important components of blasting dust were SiO2 and CaCO3 by characterization analysis. Notably, hydrophilic blasting dust has significantly more SiO2 than hydrophobic blasting dust. The density functional theory calculation predicted the wettability of water stemming containing sucrose fatty acid ester (SE) higher than that of water stemming containing other surfactants. Moreover, the water contact angle and surface tension experiments determined the addition of inorganic salts to the water stemming containing SE could increase its wettability, with the addition of Al3+ giving the best performance. The sink test and water retention experiment further prove that our synthesized water stemming has a good wetting ability on both hydrophobic and hydrophilic blasting dust. The findings of this study advance the development of reliable methods for optimizing water stemming with high wettability for removing the blasting dust.

Sepsis is a severe and life-threatening medical syndrome that can lead to organ failure and death. Despite advances in medical treatment, current therapies are often inadequate, with high septic mortality rates. Therefore, there is a critical need for reliable prognostic markers to be used in clinical settings to improve the management and outcomes of patients with sepsis. Recent studies have suggested that mitochondrial dynamics, including the processes of mitochondrial fission and fusion, are closely related to the severity of sepsis and the status of inflammation. By monitoring transcriptomic signals related to mitochondrial dynamics, new and reliable biomarkers can be engineered to more accurately predict sepsis survival risk. Such biomarkers would be invaluable in clinical settings, aiding healthcare providers in the early identification of high-risk patients and improving treatment strategies. To achieve this goal, we utilized the major mitochondrial fission regulatory protein dynamin-related protein 1 (Drp1, gene code DNM1L) and identified Drp1-associated genes that are enriched with sepsis survival genes. A 12-gene signature (GS) was established as a differentially expressed gene (DEG)-based GS. Next, we compared genes of proteins that interact with Drp1 to sepsis survival genes and identified 7 common genes, establishing a GS we term as protein-protein interaction (PPI)-based GS. To evaluate if these GSs can predict sepsis survival, we used publicly available human blood transcriptomic datasets from sepsis patients. We confirmed that both GSs can successfully predict sepsis survival in both discovery and validation cohorts with high sensitivity and specificity, with the PPI-based GS showing enhanced prognostic performance. Together, this study successfully engineers a new and validated blood-borne biomarker (PPI-based 7-gene GS) for sepsis survival risk prediction. This biomarker holds the potential for improving the early identification of high-risk sepsis patients and optimizing personalized treatment strategies to reduce sepsis mortality.

Grape maturity and yeast strains are crucial to determining young wine quality. This study evaluates the impact of three grape maturity levels with sugar contents of 22, 25, and 28°Brix combined with two S. cerevisiae strains selected from distinct terroirs on the Cabernet Sauvignon wine profile in the Ningxia Qingtongxia region in China. Physicochemical parameters and volatile aroma compounds were analyzed and quantitative descriptive analysis was performed on wine samples. The results indicated that berry ripeness primarily influenced physicochemical profiles, while aroma characteristics were affected by both grape maturity and yeast strain. Some esters and higher alcohols increased with grape maturity. Late-harvest wines scored significantly higher in aroma and taste quality than early-harvest wines. The CECA strain yielded wines with elevated medium-chain ester levels, reduced higher alcohols, improved balance and purity, and enhanced the typical aroma of blackberry, spice, and dark chocolate.

IntroductionThe striped hamster, often parasitized by ectoparasites in nature, is an ideal model for studying host-ectoparasite molecular interactions. Investigating the response to ectoparasites under laboratory conditions helps elucidate the mechanism of host adaptations to ectoparasite pressure.MethodsUsing transcriptome sequencing, we analyzed gene expression in striped hamsters after short-term (3 days) and long-term (28 days) flea (Xenopsylla cheopis) parasitism. Differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Hub genes were pinpointed using protein-protein interaction (PPI) network analysis and the MCODE in Cytoscape. Gene Set Enrichment Analysis (GSEA) was used to further clarify the functional pathways of these hub genes. Validation of DEGs was performed via RT-qPCR. Additionally, the concentrations of reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were determined using specific enzyme-linked immunosorbent assay (ELISA) detection kits for hamsters.ResultsGO analysis revealed that during early parasitism, hosts primarily responded to the ectoparasites by adjusting the expression of genes related to metabolic functions. As parasitism persisted, the immune response became prominent, activating various immune pathways against ectoparasites. KEGG analysis confirmed the ongoing roles of metabolism and immunity. Notably, the chemical carcinogenesis - reactive oxygen species pathway was upregulated during flea parasitism, with downregulation of hub genes ATP5MC1 and ATP5MC2, highlighting the importance of mitochondrial function in oxidative stress. ELISA findings revealed that on day 3, flea parasitism groups showed elevated ROS expression and reduced SOD and CAT levels compared to the control group. By day 28, only SOD expression showed a significant decrease in both parasitism groups.ConclusionThis study uncovered the dynamic changes in metabolism and immune responses of striped hamsters parasitized by Xenopsylla cheopis. Hosts adjust their physiological and immune states to optimize survival strategies during different ectoparasite stages, enhancing our understanding of host-ectoparasite interactions. This also paves the way for further research into how hosts regulate complex biological processes in response to ectoparasite challenges.

BackgroundPterygium is a complex ocular surface disease characterized by the abnormal proliferation and growth of conjunctival and fibrovascular tissues at the corneal-scleral margin. Understanding the underlying molecular mechanisms of pterygium is crucial for developing effective diagnostic and therapeutic strategies.MethodsTo elucidate the molecular mechanisms of pterygium, we conducted a differential gene expression analysis between pterygium and normal conjunctival tissues using high-throughput RNA sequencing. We identified differentially expressed genes (DEGs) with statistical significance (adjust p < 0.05, |logFC| > 1). Enrichment analyses were performed to assess the biological processes and signaling pathways associated with these DEGs. Additionally, we utilized weighted correlation network analysis (WGCNA) to select module genes and applied Random Forest (RF) and Support Vector Machine (SVM) algorithms to identify pivotal feature genes influencing pterygium progression. The diagnostic potential of these genes was validated using external datasets (GSE2513 and GSE51995). Immune cell infiltration analysis was conducted using CIBERSORT to compare immune cell populations between pterygium and normal conjunctival tissues. Quantitative PCR (qPCR) was used to confirm the expression levels of the identified feature genes. Furthermore, we identified key miRNAs and candidate drugs targeting these feature genes.ResultsA total of 718 DEGs were identified in pterygium tissues compared to normal conjunctival tissues, with 254 genes showing upregulated expression and 464 genes exhibiting downregulated expression. Enrichment analyses revealed that these DEGs were significantly associated with inflammatory processes and key signaling pathways, notably leukocyte migration and IL-17 signaling. Using WGCNA, RF, and SVM, we identified KRT10 and NGEF as pivotal feature genes influencing pterygium progression. The diagnostic potential of these genes was validated using external datasets. Immune cell infiltration analysis demonstrated significant differences in immune cell populations between pterygium and normal conjunctival tissues, with an increased presence of M1 macrophages and resting dendritic cells in pterygium samples. qPCR analysis confirmed the elevated expression of KRT10 and NGEF in pterygium tissues.ConclusionOur findings emphasize the importance of gene expression profiling in unraveling the pathogenesis of pterygium. The identification of pivotal feature gene KRT10 and NGEF provide valuable insights into the molecular mechanisms underlying pterygium progression.

BackgroundThe use of acupuncture in cancer treatment is expanding. Nevertheless, the efficacy and safety of acupuncture in alleviating cancer-related hiccups remains uncertain and inconclusive.MethodsWe conducted a systematic search across eight databases: PubMed, China National Knowledge Infrastructure Database, WanFang, China Science and Technology Journal Database, SinoMed, Web of Science, Cochrane, and Embase, covering the period from their inception to July 2023. Literature was screened based on predefined PICOS inclusion and exclusion criteria, and the risk of bias was assessed using the Cochrane Risk of Bias tool. Data synthesis was performed using Review Manager 5.3 software and R studio 4.4. Additionally, we conducted a frequency analysis of acupoint usage.ResultsA total of nine randomized controlled trials (RCTs) involving 580 patients were included in the analysis. The risk of bias assessment indicated a high risk of bias in all nine RCTs, primarily due to blinding of participants and personnel and random sequence generation (selection bias). The meta-analysis revealed that acupuncture significantly reduced the symptoms of cancer-related hiccups compared to pharmacological treatment (relative risk (RR) = 1.83, 95% confidence interval (CI) [1.53, 2.20], p

As a widely-used fluoroquinolone antibiotics, 1-Cyclopropyl-6-fluoro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid (gatifloxacin, GAT) has aroused much concern recently and it is of great importance to realize the accurate and efficient detection. Herein, the silver sulfide/reduced graphene oxide composite (Ag2S/RGO) was synthesized with one-pot method and was coated on the glassy carbon electrode to develop an effective electrochemical sensor for GAT. After the optimization of the size of Ag2S, the pH of buffer solution, and the scanning rate, the Ag2S/RGO modified electrode exhibits good linear relationship to GAT within wide ranges of 0.2 µM − 20 µM and 20 µM − 250 µM with a detection limit of 0.0667 µM. Besides, the proposed sensor shows good selectivity to GAT versus multiple interferences, including organic compounds, ions, and other antibiotics. At last, the proposed sensor was successfully applied in the GAT analysis in various real samples (including shrimp, fish, and chicken) with satisfying recoveries of 91.8 % − 102.4 %. In general, the proposed Ag2S/RGO-based electrochemical sensor provides a novel strategy for the GAT analysis, which is of significance for the development of efficient analytical techniques for antibiotics.

Radar echo extrapolation is an important approach in precipitation nowcasting which utilizes historical radar echo images to predict future echo images. In this paper, we introduce the self-attention mechanism into Trajectory Gated Recurrent Unit (TrajGRU) model. Under the sequence-to-sequence framework, we have developed a novel convolutional recurrent neural network called Self-attention Trajectory Gated Recurrent Unit (SA-TrajGRU), which incorporates the self-attention mechanism. The SA-TrajGRU model which combines spatiotemporal variant structure in TrajGRU and self-attention module is simple and effective. We evaluate our approach on the Moving MNIST-2 dataset and the CIKM AnalytiCup 2017 radar echo dataset. The experimental results show that the performance of the proposed SA-TrajGRU model is comparable to other convolutional recurrent neural network models. HSS and CSI scores of the SA-TrajGRU model are higher than scores of other models under the radar echo threshold of 25 dBZ, indicating that the SA-TrajGRU model has the most accurate prediction results under this threshold.

Background: Clinical research data showed a series of adverse events in the delivery period of primary immune thrombocytopenia (ITP) patients, including high cesarean section rate. Consensus report proposed that for patients with platelet count below 50 × 109/L, prednisone or intravenous immunoglobulins (IVIg) can be given to raise the platelet count in third trimester in preparation for labor.Objectives: To evaluate the effect of low-dose prednisone or IVIg therapy on delivery outcomes in patients with ITP.Study design: This was a cohort study that included pregnant women with ITP from January 2017 to December 2022. Patients with platelet counts of (20–50) ×109/L at the time of delivery (≥34 weeks) and who had not received any medication before were enrolled in the study. Patients were divided into the pre-delivery medication group (oral prednisone or IVIg) and untreated group according to their preferences. The differences in vaginal delivery rate, postpartum bleeding rate, and platelet transfusion volume between the two groups were compared using t-test, Wilcoxon rank-sum test, and χ2 test. Logistic regression analysis was used to identify the factors affecting vaginal delivery rate and postpartum bleeding rate, and multiple linear regression analysis was used to identify the factors affecting platelet transfusion volume.Results: During the study period, a total of 96 patients with ITP were enrolled, including 70 in the pre-delivery medication group and 26 in the untreated group. The platelet count of pre-delivery medication group was 54.8 ± 34.5 × 109/L, which was significantly higher than that of untreated group 34.4 ± 9.0 × 109/L (p = .004). The vaginal delivery rate of the medication group was higher than the untreated group [60.0% (42/70) vs. 30.8% (8/26), χ2 = 6.49, p = .013]. After adjusting for the proportion of multiparous women and gestational weeks, the results showed that medication therapy during the peripartum period was associated with vaginal delivery (OR = 4.937, 95% CI: 1.511–16.136, p = .008). The postpartum bleeding rates were 22.9% (16/70) and 26.9% (7/26) in the medication group and untreated group, respectively, with no significant difference between the two groups (χ2 = 0.17, p = .789), while the platelet transfusion volume was lower in the medication group than untreated group [(1.1 ± 1.0) vs. (1.6 ± 0.8) U].Conclusion: Pre-delivery medication therapy can increase vaginal delivery rate, reduce platelet transfusion volume, but does not decrease the incidence of postpartum hemorrhage.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections tend to cause severe symptoms in individuals with certain pre-existing conditions, such as advanced age, comorbidities, and being male. Studies have shown direct correlations between these factors and infection severity. Other factors like inflammation and oxidative stress and their concomitant cytokine expressions further complicate disease severity. Severity in elderly persons is not only helped by age-related inflammatory conditions but exacerbated by a lack of certain immune-boosting nutrients. Retrospective research often focuses on single-nutrient interventions, while this review emphasizes multi-nutrient strategies. Particular emphasis is placed on the synergistic effects of multiple nutrients such as Vitamin D, Zinc, Selenium (Se), Omega-3 PUFAs, probiotics, dietary flavonoids, and peptides in ameliorating the dual inflammation and oxidative stress pathways, especially in high-risk groups like elderly persons. The primary mechanism by which these nutrients exert their effect is the modulation of the virus' replication through interference with the RNA export machinery, among other potential pathways. Quantitative data supports the review's conclusions, with studies showing that 85 % of severe COVID-19 cases are linked to Vitamin D deficiency, while Se's supplementation reduces viral replication by 20 %. Therefore, when aging is a risk factor for an infection, consuming health-promoting diets and healthy lifestyles are good tips, especially for elderly persons. Future research should explore the long-term effects of nutritional interventions, particularly how multi-nutrient approaches can assist in managing post-COVID syndromes, as supported by studies on Omega-3 PUFAs and their ability to reduce cytokine levels by 30 %.

Abstract Background Fatigue is one of the most common neurological symptoms reported post coronavirus disease 2019 (COVID-19) infection. In order to establish effective early intervention strategies, more emphasis should be placed on the correlation between fatigue and cortical neurophysiological changes, especially in healthcare workers, who are at a heightened risk of COVID-19 infection. Methods A prospective cohort study was conducted involving 29 COVID-19 medical workers and 24 healthy controls. The assessment included fatigue, sleep and health quality, psychological status, and physical capacity. Functional near-infrared spectroscopy (fNIRS) was employed to detect activation of brain regions. Bilateral primary motor cortex (M1) excitabilities were measured using single- and paired-pulse transcranial magnetic stimulation. Outcomes were assessed at 1, 3, and 6 months into the disease course. Results At 1-month post-COVID-19 infection, 37.9% of patients experienced severe fatigue symptoms, dropping to 10.3% at 3 months. Interestingly, the remarkable decreased activation/excitability of bilateral prefrontal lobe (PFC) and M1 were closely linked to fatigue symptoms after COVID-19. Notably, greater increase in M1 region excitability correlated with more significant fatigue improvement. Re-infected patients exhibited lower levels of brain activation and excitability compared to single-infection patients. Conclusions Both single infection and reinfection of COVID-19 lead to decreased activation and excitability of the PFC and M1. The degree of excitability improvement in the M1 region correlates with a greater recovery in fatigue. Based on these findings, targeted interventions to enhance and regulate the excitability of M1 may represent a novel strategy for COVID-19 early rehabilitation. Trial registration: The Ethics Review Committee of Xijing Hospital, No. KY20232051-F-1; www.chictr.org.cn , ChiCTR2300068444.

Abstract Backgrounds Mycoplasma pneumoniae (M. pneumoniae) is a common pathogen causing respiratory diseases in children. This study aimed to characterize epidemiological and disease severity shifts of M. pneumoniae: infections in Guangzhou, China during and after the coronavirus disease 2019 (COVID-19) pandemic. Methods Throat swab samples were obtained from 5405 hospitalized patients with symptoms of acute respiratory infections to detect M. pneumoniae. Differences in epidemiological and clinical characteristics of M. pneumoniae: infections were investigated during 2020–2022 and after COVID-19 pandemic (2023). Results M. pneumoniae were detected in 849 (15.6%, 849/5405) patients. The highest annual positive rate was 29.4% (754/2570) in 2023, followed by 5.3% (72/1367) in 2022, 1.2% (12/1015) in 2021, and 2.0% (11/553) in 2020, with significantly increasing annual prevalence from 2020 to 2023. M. pneumoniae incidence peaked between July and December post-COVID-19 pandemic in 2023, with the highest monthly positive rate (56.4%, 165/293). Clinical characteristics and outcomes of patients with M. pneumoniae did not vary between periods during and after COVID-19 pandemic except that patients with M. pneumoniae post-COVID-19 pandemic were more likely to develop fever. Patients with severe M. pneumoniae pneumonia (SMPP) were more likely to develop respiratory complications, myocardial damage, and gastrointestinal dysfunction than those with non-SMPP. Patients with SMPP had lower lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, and higher IL-4, IL-6, IL-10 levels than those with non-SMPP. Bronchoalveolar lavage fluid specimens from infected patients were obtained to identify macrolide resistance mutations. Macrolide-resistant M. pneumoniae (MRMP) proportion in 2023 was 91.1% (215/236). Conclusion Outbreaks of M. pneumoniae: occurred in Guangzhou, China in 2023 upon Non-pharmaceutical interventions easing. Despite the increasing incidence of M. pneumoniae, the disease severity remained similar during and after the COVID-19 pandemic.

Abstract Associations between migraine and retinal vascular occlusion have been reported, but there is no large-scale and comprehensive study. Therefore, we aimed to determine risks of retinal vascular occlusion in patients with migraine. Using the Taiwan National Health Insurance Research Database from 2009 to 2020, we enrolled 628,760 patients with migraine and 628,760 matched individuals without migraine. Study outcomes were diagnoses of retinal vascular occlusion, including retinal artery occlusion (RAO) and retinal vein occlusion (RVO). Adjusted hazard ratio (aHR) of retinal vascular occlusion related to migraine was estimated. The cumulative incidences of subsequent retinal vascular occlusion, RAO, and RVO were significantly higher in migraine patients compared with controls (0.31% vs. 0.21%; 0.09% vs. 0.05%; 0.22% vs. 0.17%; all p

Abstract Previous studies have reported that the significant association between serum calcium and mortality substantially in patients, especially among those with intensive care unit (ICU). And In diabetes mellitus, congestive heart failure (CHF) is a significant comorbidity. We aim to evaluate the association between serum calcium levels and in-hospital mortality among patients with diabetes and congestive heart failure. The participants in this study were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. To scrutinize potential associations between serum calcium levels and in-hospital mortality, a comprehensive analysis encompassing multivariate logistic regression, cubic spline function model, threshold effect analysis, and subgroup analysis was performed. This retrospective cohort study encompassed 7063 patients, among whom the in-hospital mortality stood at 12.2%. In the multivariate logistic regression, adjusted odds ratios (ORs) were contrasted with the reference category Q6 (8.8–9.1 mg/dL) for serum calcium levels and in-hospital mortality. The adjusted ORs for Q1 (≤ 7.7 mg/dL), Q2 (7.7–8 mg/dL), and Q7 (≥ 9.1 mg/dL) were 1.69 (95% CI 1.17–2.44, p = 0.005), 1.62 (95% CI 1.11–2.36, p = 0.013), and 1.57 (95% CI 1.1–2.24, p = 0.012) respectively. The dose–response analysis uncovered a U-shaped relationship between serum calcium levels and in-hospital mortality in diabetic patients with heart failure. Subgroup analyses confirmed result stability notwithstanding the influence of diverse factors. Our investigation revealed a U-shaped correlation between serum calcium levels and in-hospital mortality in diabetes patients with congestive heart failure, pinpointing a significant inflection point at 9.05 mg/dL.

Abstract Background Previous studies, including Mendelian randomization (MR), have demonstrated type 2 diabetes (T2D) and glycemic traits are associated with increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD). However, few studies have explored the underlying pathway, such as the role of iron homeostasis. Methods We used a two-step MR approach to investigate the associations of genetic liability to T2D, glycemic traits, iron biomarkers, and liver diseases. We analyzed summary statistics from various genome-wide association studies of T2D (n = 933,970), glycemic traits (n ≤ 209,605), iron biomarkers (n ≤ 246,139), MASLD (n ≤ 972,707), and related biomarkers (alanine aminotransferase (ALT) and proton density fat fraction (PDFF)). Our primary analysis was based on inverse-variance weighting, followed by several sensitivity analyses. We also conducted mediation analyses and explored the role of liver iron in post hoc analysis. Results Genetic liability to T2D and elevated fasting insulin (FI) likely increased risk of liver steatosis (ORliability to T2D: 1.14 per doubling in the prevalence, 95% CI: 1.10, 1.19; ORFI: 3.31 per log pmol/l, 95% CI: 1.92, 5.72) and related biomarkers. Liability to T2D also likely increased the risk of developing liver cirrhosis. Genetically elevated ferritin, serum iron, and liver iron were associated with higher risk of liver steatosis (ORferritin: 1.25 per SD, 95% CI 1.07, 1.46; ORliver iron: 1.15 per SD, 95% CI: 1.05, 1.26) and liver cirrhosis (ORserum iron: 1.31, 95% CI: 1.06, 1.63; ORliver iron: 1.34, 95% CI: 1.07, 1.68). Ferritin partially mediated the association between FI and liver steatosis (proportion mediated: 7%, 95% CI: 2–12%). Conclusions Our study provides credible evidence on the causal role of T2D and elevated insulin in liver steatosis and cirrhosis risk and indicates ferritin may play a mediating role in this association.

Abstract High-grade B-cell lymphoma (HGBCL), the subtype of non-Hodgkin lymphoma, to be relapsed or refractory in patients after initial therapy or salvage chemotherapy. Dual dysregulation of MYC and BCL2 is one of the important pathogenic mechanisms. Thus, combined targeting of MYC and BCL2 appears to be a promising strategy. Dihydroorotate dehydrogenase (DHODH) is the fourth rate-limiting enzyme for the de novo biosynthesis of pyrimidine. It has been shown to be a potential therapeutic target for multiple diseases. In this study, the DHODH inhibitor brequinar exhibited growth inhibition, cell cycle blockade, and apoptosis promotion in HGBCL cell lines with MYC and BCL2 rearrangements. The combination of brequinar and BCL2 inhibitors venetoclax had a synergistic inhibitory effect on the survival of DHL cells through different pathways. Venetoclax could upregulate MCL-1 and MYC expression, which has been reported as a resistance mechanism of BCL2 inhibitors. Brequinar downregulated MCL-1 and MYC, which could potentially overcome drug resistance to venetoclax in HGBCL cells. Furthermore, brequinar could downregulate a broad range of genes, including ribosome biosynthesis genes, which might contribute to its anti-tumor effects. In vivo studies demonstrated synergetic tumor growth inhibition in xenograft models with brequinar and venetoclax combination treatment. These results provide preliminary evidence for the rational combination of DHODH and BCL2 blockade in HGBCL with abnormal MYC and BCL2.

Bioactive peptides (BPs) are characterized by their low molecular weight, low toxicity, ease of absorption, and high biological activity. Additionally, they exhibit various beneficial properties such as antibacterial and anti-inflammatory effects. However, their practical applications in food, pharmaceutical, and other industries are limited due to their low stability, rapid degradation in the gastrointestinal tract, and poor bioavailability. Carriers offer a potential solution by improving the stability and bioavailability of BPs. Despite advancements, existing carriers with targeted and controlled release capabilities often fail to meet the specific requirements of certain BPs, such as achieving a high encapsulation rate and maximizing bioavailability. Furthermore, there is a notable lack of academic research exploring the preparation methods, characterization techniques, and application scenarios of these carriers. This review critically evaluates the limitations of existing carriers and emphasizes the need for novel carriers. This review provides a comprehensive discussion of the functional properties, preparation methods, and characterization techniques of novel carriers. The advantages and disadvantages of these carriers are also summarized to assist in selecting the most suitable carrier for specific application scenarios. This information aims to address challenges associated with the effective delivery of BPs, advancing their utility across various industries.

The emergence of extracellular vesicles (EVs), which are natural lipid bilayer membrane structures facilitating intercellular substance and information exchange, has sparked innovative approaches in drug development and carrier enhancement. Plant-derived EVs notably offer advantages including low preparation cost, low immunogenicity, flexible drug delivery, high stability, good tissue permeability, and high inherent medicinal value compared to their animal-derived counterparts. Despite these promising attributes, the research on plant-derived EVs remains fragmented and lacks comprehensive synthesis. This review aims to address this gap by summarizing the isolation methods, biological characteristics, and storage techniques of plant-derived EVs. Additionally, we explore the potential of plant-derived EVs as therapeutic agents and drug carriers for treating various diseases. Finally, we delineate the current impediments to plant-derived EV development and highlight future research directions. By providing a detailed overview, we hope to facilitate further research and application in this emerging field.

To attain sustainable development goals and understand urban growth patterns, continuous and precise monitoring of built-up area heights is essential. This helps reveal how urban form evolution impacts the thermal environment. Previous research often used isolated images, ignoring the temporal dimension of thermal infrared and reflectance data from Landsat sensors. Additionally, cost-effective and efficient methods for reconstructing time-series built height are lacking. To fill this knowledge gap, we utilized Landsat time-series data to reconstruct the yearly trends in urban form in Beijing, China, spanning from 1990 to 2020. Continuous Change Detection and Classification (CCDC) time series analysis method was used to identify urban growth and renewal years. Employing a reference height for 2020 and logical reasoning method, we reconstructed the annual dynamics of built-up heights, pinpointing years of significant change. Finally, we analyzed the alterations in urban form over the past three decades and their impact on surface temperature changes. Our change detection method achieved an overall accuracy of 86 %, demonstrating its effectiveness in determining the year of change. When compared with data from Lianjia and LiDAR point cloud, our height reconstruction method showed impressive accuracy, with R2 values of 0.9773 and 0.9526, respectively. Analysis of summer and winter LST values revealed distinct temperature patterns across different building heights, with mid-rise buildings exhibiting the highest LST in summer and low-rise buildings registering the highest LST in winter. During periods of urban growth, both mean and amplitude values of LST increased, while during urban renewal (demolition), they decreased. The date of annual temperature peaks advanced during urban growth but delayed during urban renewal (demolition). Our time series analysis framework offers a new method for understanding the yearly dynamics of urban form and its influence on surface temperature, with potential applications in carbon emission and urban climate modeling studies.