Hetastarch-stabilized polypyrrole with hyperthermia-enhanced release and catalytic activity for synergistic antitumor therapy.

Fenton catalytic medicine that catalyzes the production of ·OH without external energy input or oxygen as a substrate has reshaped the landscape of conventional cancer therapy in recent decades, yet potential biosafety concerns caused by non-safety-approved components restrict their clinical translation from the bench to the bedside. Herein, to overcome this dilemma, we elaborately utilizate safety-approved hetastarch, which has been extensively employed in the clinic as a plasma substitute, as a stabilizer participating in the copper chloride-initiated polymerization of pyrrole monomer before loading it with DOX. The constructed DOX-loaded hetastarch-doped Cu-based polypyrrole (HES@CuP-D) catalyzes the excess H2O2 in tumor cells to ·OH through a Cu+-mediated Fenton-like reaction, which not only causes oxidative damage to tumor cells but also leads to the structural collapse and DOX release. Additionally, HES@CuP-D together with laser irradiation reinforces tumor killing efficiency by hyperthermia-enhanced catalytic activity and -accelerated drug release. As a result, the developed HES@CuP-D provides a promising strategy for Fenton catalytic therapy with negligible toxicity to the body.

Directed osteogenic differentiation of human bone marrow mesenchymal stem cells via sustained release of BMP4 from PBVHx-based nanoparticles.

Bone Morphogenetic Protein 4 (BMP4) is crucial for bone and cartilage tissue regeneration, essential in medical tissue engineering, cosmetology, and aerospace. However, its cost and degradation susceptibility pose significant clinical challenges. To enhance its osteogenic activity while reducing dosage and administration frequency, we developed a novel long-acting BMP4 delivery system using poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PBVHx) nanoparticles with soybean lecithin-modified BMP4 (sBP-NPs). These nanoparticles promote directed osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) through sustained BMP4 release. sBP-NPs exhibited uniform size (100-200 nm) and surface charges, with higher BMP4 entrapment efficiency (82.63 %) compared to controls. After an initial burst release within 24 h, sBP-NPs achieved 80 % cumulative BMP4 release within 20 days, maintaining levels better than control BP-NPs with unmodified BMP4. Co-incubation and nanoparticle uptake experiments confirmed excellent biocompatibility of sBP-NPs, promoting hBMSC differentiation towards osteogenic lineage with increased expression of type I collagen, calcium deposition, and ALP activity (> 20,000 U/g protein) compared to controls. Moreover, hBMSCs treated with sBP-NPs exhibited heightened expression of osteogenic genetic markers, surpassing control groups. Hence, this innovative strategy of sustained BMP4 release from sBP-NPs holds potential to revolutionize bone regeneration in minimally invasive surgery, medical cosmetology or space environments.

A Sn-Based Hybrid Ferroelastic Semiconductor with High-Temperature Dielectric Switching.

Organic-inorganic halide hybrids have been extensively developed and used in optoelectronic devices because of their superior performance such as ease of assembly, flexible structural tunability, and excellent optoelectronic properties. Ferroelastic strain might be used to modulate and control photoelectric properties such as photovoltaic voltage, while organic-inorganic hybrid ferroelastic semiconductors remain relatively unexplored. Herein, we successfully design a new Sn-base, lead-free hybrid ferroelastic semiconductor, [TPMA]2[SnCl6] (TPMA = benzyl trimethylammonium). It undergoes a high-temperature -3mF-1-type ferroelastic phase transition at 408 K, and intriguingly, its ferroelastic domains can be simultaneously switched under the stimulation of external heat and stress. The ferroelastic phase transition might be derived from the order-disorder transition of organic cations during heating and cooling. Moreover, [TPMA]2[SnCl6] also demonstrates a high-temperature dielectric switching property around 408 K, which has good stability and reproducibility. With those benefits, [TPMA]2[SnCl6] shows great potential in applications such as energy storage devices, optoelectronic devices, shape memory, intelligent switches, and so on.

Correlation analysis of central arterial pressure parameters and the severity of atherosclerotic lesions in coronary arteries: A retrospective study.

To investigate the correlation between central arterial pressure (CAP) parameters and the severity of atherosclerotic lesions in the coronary arteries, understand the value of CAP in assessing the risk of coronary heart disease (CHD), and provide a theoretical basis for the prevention and treatment of CHD. Between January 2021 and January 2022, 224 patients admitted to our hospital for complete coronary angiography (CAG) were included in this retrospective study. CAP parameters, including central systolic pressure (CSP), diastolic pressure (CDP), and pulse pressure (CPP), and Gensini scores were collected; the association between CAP parameters and the severity of coronary lesions was analyzed using the Pearson correlation coefficient (r) and multivariate regression analysis. CPP was significantly higher in the coronary multi-branch lesion group than in the single-branch lesion group in patients with CHD (P < .05). CSP, CDP, and CPP were significantly higher in the high Gensini score group than in the low Gensini score group for coronary vascular lesions; furthermore, CSP and CPP were significantly higher in the high Gensini score group than in the medium Gensini score group (P < .05). Pearson correlation analysis showed that CSP and CPP were positively and CDP was negatively correlated with the severity of coronary artery lesions in patients with CHD (P < .05). Logistic regression analysis showed that a history of diabetes, CSP, CDP, and CPP were independent risk factors for severe atherosclerotic lesions in the coronary arteries (P < .05). noninvasive CAP-related indices, such as CSP, CDP, and CPP, are independently correlated with and can be used to predict the severity of coronary lesions in patients with CHD, which may be beneficial for guiding clinical diagnosis and treatment.

Identification of novel STAT3 inhibitors for liver fibrosis, using pharmacophore-based virtual screening, molecular docking, and biomolecular dynamics simulations.

The signal transducer and activator of transcription 3 (STAT3) plays a fundamental role in the growth and regulation of cellular life. Activation and over-expression of STAT3 have been implicated in many cancers including solid blood tumors and other diseases such as liver fibrosis and rheumatoid arthritis. Therefore, STAT3 inhibitors are be coming a growing and interesting area of pharmacological research. Consequently, the aim of this study is to design novel inhibitors of STAT3-SH3 computationally for the reduction of liver fibrosis. Herein, we performed Pharmacophore-based virtual screening of databases including more than 19,481 commercially available compounds and in-house compounds. The hits obtained from virtual screening were further docked with the STAT3 receptor. The hits were further ranked on the basis of docking score and binding interaction with the active site of STAT3. ADMET properties of the screened compounds were calculated and filtered based on drug-likeness criteria. Finally, the top five drug-like hit compounds were selected and subjected to molecular dynamic simulation. The stability of each drug-like hit in complex with STAT3 was determined by computing their RMSD, RMSF, Rg, and DCCM analyses. Among all the compounds Sa32 revealed a good docking score, interactions, and stability during the entire simulation procedure. As compared to the Reference compound, the drug-like hit compound Sa32 showed good docking scores, interaction, stability, and binding energy. Therefore, we identified Sa32 as the best small molecule potent inhibitor for STAT3 that will be helpful in the future for the treatment of liver fibrosis.

Construction of the metabolism-related models for predicting prognosis and infiltrating immune phenotype in lung squamous cell carcinoma.

Purpose: Cancers often display disorder metabolism, which closely related to the poor outcome of patients. We aimed to establish prognostic models using metabolism-associated genes, and identify the key factor involved in metabolism in lung squamous cell carcinoma (LUSC). Materials and Methods: R package 'TCGA biolinks' was used to download the mRNA sequencing data of LUSC from TCGA. The clusterProfiler package was performed to analyze biological pathways. The online tool GEPIA2 and cox regression method were applied to identify the two gene lists associated with metabolism and prognosis of LUSC. The lasso modeling was conducted to establish prognostic models. The quantiseq method was used to identify the cellular abundance of expression matrix in TCGA-LUSC dataset. Immunohistochemistry and western blotting were done to evaluate the STXBP1 expression in LUSC samples. Lactate assay and ATP detection were performed to assess metabolic effect, and CCK8 assay was done to test cell proliferation in the LUSC cells with overexpression and suppression of STXBP1. Results: Two lists of survival-metabolism-associated genes (11 and 28 genes) were identified and applied in the prognostic model 1 and model 2 construction from TCGA-LUSC dataset. High-risk LUSC patients associated with poor survival in the training cohort and the test cohort of both model 1 and model 2. Higher ROC values for 10- year survival was shown in model 2 than in model 1. In addition, macrophage M1, macrophage M2, neutrophil, and T regulatory cell were enriched in the high-risk group of model 2. STXBP1 was the only optimized gene in both model 1 and model 2, and related to the poor outcome of LUSC patients. Furthermore, STXBP1 associated with infiltrating immune cells, and increased lactate, ATP levels, and cell proliferation. Conclusion: Our finding provides the metabolism-associated models to predict prognosis of LUSC patients. STXBP1, as the key optimized gene in the model, promotes metabolic progress to increase lactate and ATP levels in LUSC cells.

Truncated DNM1 variant underlines developmental delay and epileptic encephalopathy.

Background: Developmental and epileptic encephalopathies (DEEs) signify a group of heterogeneous neurodevelopmental disorder associated with early-onset seizures accompanied by developmental delay, hypotonia, mild to severe intellectual disability, and developmental regression. Variants in the DNM1 gene have been associated with autosomal dominant DEE type 31A and autosomal recessive DEE type 31B. Methods: In the current study, a consanguineous Pakistani family consisting of a proband (IV-2) was clinically evaluated and genetically analyzed manifesting in severe neurodevelopmental phenotypes. WES followed by Sanger sequencing was performed to identify the disease-causing variant. Furthermore, 3D protein modeling and dynamic simulation of wild-type and mutant proteins along with reverse transcriptase (RT)-based mRNA expression were checked using standard methods. Results: Data analysis of WES revealed a novel homozygous non-sense variant (c.1402G>T; p. Glu468*) in exon 11 of the DNM1 gene that was predicted as pathogenic class I. Variants in the DNM1 gene have been associated with DEE types 31A and B. Different bioinformatics prediction tools and American College of Medical Genetics guidelines were used to verify the identified variant. Sanger sequencing was used to validate the disease-causing variant. Our approach validated the pathogenesis of the variant as a cause of heterogeneous neurodevelopmental disorders. In addition, 3D protein modeling showed that the mutant protein would lose most of the amino acids and might not perform the proper function if the surveillance non-sense-mediated decay mechanism was skipped. Molecular dynamics analysis showed varied trajectories of wild-type and mutant DNM1 proteins in terms of root mean square deviation, root mean square fluctuation and radius of gyration. Similarly, RT-qPCR revealed a substantial reduction of the DNM1 gene in the index patient. Conclusion: Our finding further confirms the association of homozygous, loss-of-function variants in DNM1 associated with DEE type 31B. The study expands the genotypic and phenotypic spectrum of pathogenic DNM1 variants related to DNM1-associated pathogenesis.

Combination Therapies to Improve the Efficacy of Immunotherapy in Triple-negative Breast Cancer.

Immune checkpoint inhibition combined with chemotherapy is currently approved as first-line treatment for patients with advanced PD-L1-positive triple-negative breast cancer (TNBC). However, a significant proportion of metastatic TNBC is PD-L1-negative and, in this population, chemotherapy alone largely remains the standard-of-care and novel therapeutic strategies are needed to improve clinical outcomes. Here, we describe a triple combination of anti-PD-L1 immune checkpoint blockade, epigenetic modulation thorough bromodomain and extra-terminal (BET) bromodomain inhibition (BBDI), and chemotherapy with paclitaxel that effectively inhibits both primary and metastatic tumor growth in two different syngeneic murine models of TNBC. Detailed cellular and molecular profiling of tumors from single and combination treatment arms revealed increased T- and B-cell infiltration and macrophage reprogramming from MHCIIlow to a MHCIIhigh phenotype in mice treated with triple combination. Triple combination also had a major impact on gene expression and chromatin profiles shifting cells to a more immunogenic and senescent state. Our results provide strong preclinical evidence to justify clinical testing of BBDI, paclitaxel, and immune checkpoint blockade combination.

Sublobar resection reduces the risk of postoperative cognitive dysfunction compared with lobectomy.

OBJECTIVES: Sublobar resection, including wedge resection and segmentectomy, is non-inferior to lobectomy in early-stage non-small cell lung cancer treatment. We aimed to compare the risk of postoperative cognitive dysfunction (POCD) between sublobar resection and lobectomy. METHODS: We conducted a prospective cohort study. Patients with sublobar resection or lobectomy were divided into the sublobar group or the lobar group, respectively. Cognition was assessed before and after surgery with Montreal Cognitive Assessment and Minimum Mental State Examination tests. POCD is defined as Z score of Montreal Cognitive Assessment change ≤-1.96. Propensity score matching (PSM) was performed to make demographics well-balanced between the 2 groups. RESULTS: A total of 335 patients were enrolled. Both the postoperative 1-day POCD rate (sublobar 5.5% vs lobar 18.2%, P < 0.001) and the postoperative 1-month POCD rate (sublobar 7.9% vs lobar 21.8%, P < 0.001) were significantly lower in the sublobar group compared with lobar group, with demographics unbalanced between the 2 groups. In the 133 demographics-matched pairs obtained by PSM, both the postoperative 1-day POCD rate (sublobar 5.3% vs lobar 17.3%, P = 0.005) and the postoperative 1-month POCD rate (sublobar 8.3% vs lobar 18.8%, P = 0.018) remained significantly lower in the sublobar group than in the lobar group. The incidences of postoperative 1-day (P = 0.109) and postoperative 1-month (P = 0.026) Minimum Mental State Examination abnormity were also lower in the sublobar group than in the lobar group but only the latter was with statistical significance after PSM. CONCLUSIONS: Sublobar resection has an advantage over lobectomy in preventing POCD. Our findings might be a reference for selecting the most suitable type of resection for non-small-cell lung cancer patients.

Dual Breaking of Molecular Orbitals and Spatial Symmetry in an Optically Controlled Ferroelectric.

As particles carry quantified energy, photon radiation enables orbital transitions of energy levels, leading to changes in the spin state of electrons. The resulting switchable structural bistability may bring a new paradigm for manipulating ferroelectric polarization. However, the studies on molecular orbital breaking in the ferroelectric field remain blank. Here, for the first time, a new mechanism of ferroelectrics-dual breaking of molecular orbitals and spatial symmetry, demonstrated in a photochromic organic crystal with light-induced polarization switching, is formally proposed. By alternating the ultraviolet/visible light irradiation, the states of electron spin and the radial distribution p atomic orbitals experience a change, showing a reversible switch from "shoulder-to-shoulder" form to a "head-to-head" form. This reflects a reversible conversion between π and σ bonds, which induces and couples with the variation of spatial symmetry. The intersection of spatial symmetry breaking and molecular orbital breaking in ferroelectrics present in this work will be more conducive to data encryption and anticounterfeiting.

The incidence of malignancies in asbestosis with chrysotile exposure: a large Chinese prospective cohort study.

Background: Asbestos exposure is closely related to the occurrence and development of various malignancies. This prospective cohort study aimed to evaluate the incidence rate and potential risk factors in a cohort of asbestosis patients in China. Methods: The incidence of malignancies was determined in patients who had been exposed to chrysotile asbestos and diagnosed with asbestosis sequentially at Beijing Chaoyang Hospital from 1 January 2007 to 31 December 2019. Cox regression analyses were used to analyze the correlations between clinical variables and asbestosis combined with malignancies. Results: A total of 618 patients with asbestosis were identified, of whom 544 were eligible for analysis. Among them, 89 (16.36%) were diagnosed with various malignancies. The standardized incidence ratios (SIRs) of patients with asbestosis combined with malignancies were 16.61, 175, 5.23, and 8.77 for lung cancer, mesothelioma, breast cancer, and endometrial carcinoma, respectively. The risks of all malignancies and lung cancer increased with initial exposure before 17 years old, longer asbestos exposure, and smoking. Conclusions: The SIRs of patients with asbestosis-related malignancies were significantly increased in lung cancer, mesothelioma, breast cancer, and endometrial carcinoma in a hospital-based Chinese cohort. Smoking and the duration of asbestos exposure increased the risk of lung cancer.

4D printed tri-segment nerve conduit using zein gel as the ink for repair of rat sciatic nerve large defect.

Zein has enormous potential for application in biomedical field due to biodegradation and biocompatibility, we have recently prepared zein gel as a possible 3D printing ink. Our previous studies found that the pore structure in zein material can reduce early inflammation, promote the polarization of macrophages toward the M2 phenotype, and accelerate nerve regeneration. To further explore the role of zein in nerve repair, we used 4D printing technique to create nerve conduits with zein protein gel, and designed 2 types of tri-segment conduits with different degradation rates. Structural parts printed in support baths with higher water content show faster degradation rates than those printed in support baths with lower water content. The conduits that degraded quickly at both ends and slowly in the middle (CB75-CB40-CB75) and the conduits that degraded slowly at both ends and quickly in the middle (CB40-CB75-CB40) were 4D printed, respectively. Animal experiments suggest that the CB75-CB40-CB75 conduit is better for nerve repair, which may be because its degradation pattern can match to the pattern of nerve regeneration better. Our new strategy through 4D printing indicated that fine modulation in conduit degradation can affect efficacy of nerve repair significantly.

Production performance and rumen bacterial community structure of Hu sheep fed fermented spent mushroom substrate from Pleurotus eryngii.

This study aimed to investigate the effect of fermented spent mushroom substrate from Pleurotus eryngii (SMPE) supplementation on production performance, meat quality and rumen bacterial community structure of Hu sheep. 120 2-month-old Hu sheep with average body weight [(13.50 ± 3.10) kg] were selected and randomly divided into 4 groups with 3 replicates per group and 10 sheep per replicate. The control group (RL1) was fed a total mixed ration (TMR), and group RL2, RL3 and RL4 were fed the basal diets supplemented with 15%, 30% and 45% fermented SMPE, respectively. The pretest period lasted for 10 days and the test period lasted for 150 days. The results showed that: (1) Difference (p < 0.05) was observed in average daily feed intake (ADFI) and feed conversion ratio (FCR) between RL2 and RL4 groups. The eye muscle area (EMA) and grade rule (GR) values in RL2 and RL3 were significantly higher than those in RL1 and RL4 groups (p < 0.05). (2) The contents of threonine, valerine, leucine, lysine, histidine, essential amino acids, flavor amino acids, aspartic acid, serine, glutamic acid and arginine of the longissimus dorsi muscle in RL2 and RL3 groups were significantly higher than RL1 and RL4 (p < 0.05). (3) A total of 1,202,445 valid sequences were obtained from rumen of Hu sheep fed different amounts of fermented feed, and the valid sequences were clustered into 9824 Operational Taxonomic Units (OTUs). (4) α diversity analysis showed that the richness and diversity of rumen bacterial communities in Hu sheep in RL1, RL2, RL3 and RL4 groups were significantly higher than RL0 (raw materials of fermented SMPE) group (p < 0.05). ß diversity analysis showed that the bacterial community structure was the most different between RL0 and RL3. (5) At the genus level, compared with RL1, the relative abundance of Christensenellaceae R-7 in RL3 group decreased significantly by 33.59%, the relative abundance of Prevotellaceae UCG001 in RL2, RL3 and RL4 decreased significantly by 50.41%, 62.24% and 49.17%, respectively, and the relative abundance of Ruminococcaceae NK4A214 in RL2 group increased significantly by 35.01% (p < 0.05). In summary, the addition of fermented SMPE to TMR can significantly improve the production performance, meat quality and rumen bacterial community diversity and abundance of Hu sheep.

Synergistic Effects of Water Management and Silicon Foliar Spraying on the Uptake and Transport Efficiency of Cadmium in Rice (Oryza sativa L.).

To study the synergistic effects of water management and silicon (Si) foliar spraying on the uptake and transport of cadmium (Cd) in rice, we designed four treatments: conventional intermittent flooding + no Si foliar spraying (CK), continuous flooding throughout the growth stage + no Si foliar spraying (W), conventional intermittent flooding + Si foliar spraying (Si) and continuous flooding throughout the growth stage + Si foliar spraying (WSi). The results show that WSi treatment reduced the uptake and translocation of Cd by rice and significantly reduced the brown rice Cd content, with no effect on rice yield. Compared with CK, the Si treatment increased the net photosynthetic rate (Pn), stomatal conductance (Gs) and transpiration rate (Tr) of rice by 6.5-9.4%, 10.0-16.6% and 2.1-16.8%, respectively. The W treatment decreased these parameters by 20.5-27.9%, 8.6-26.8% and 13.3-23.3%, respectively, and the WSi treatment decreased them by 13.1-21.2%, 3.7-22.3% and 2.2-13.7%, respectively. The superoxide dismutase (SOD) and peroxidase (POD) activity decreased by 6.7-20.6% and 6.5-9.5%, respectively, following the W treatment. Following the Si treatment, SOD and POD activity increased by 10.2-41.1% and 9.3-25.1%, respectively, and following the WSi treatment, they increased by 6.5-18.1% and 2.6-22.4%, respectively. Si foliar spraying ameliorated the detrimental effects of continuous flooding throughout the growth stage on photosynthesis and antioxidant enzyme activity. We conclude that synergistic continuous flooding throughout the growth stage, combined with Si foliar spraying, can significantly block Cd uptake and translocation and is therefore an effective means of reducing the accumulation of Cd in brown rice.

Evaluation of the clinical characteristics and prognostic factors of gastrointestinal non-Hodgkin lymphoma based on anatomical sites and histological subtype.

BACKGROUND: This study aimed to analyze the clinical characteristics and prognostic factors of patients with non-Hodgkin lymphoma (NHL) in the gastrointestinal tract. METHODS: This study investigated patients (n = 456) with gastrointestinal tract NHL who had been initially treated in our hospital between January 2018 and December 2021. We compared clinical characteristics and prognostic factors according to the anatomic site of involvement and histologic subtypes. RESULTS: Gastrointestinal tract involvement was more common in B-cell than T-cell lymphomas (91.7% versus 8.3%). The intestine (n = 237) involvement was more common than the stomach (n = 219). Patients with T-cell lymphoma were more likely to present with advanced disease and B symptoms than B-cell lymphoma. Subgroup survival analysis was conducted for 358 patients whose follow-up time was more than 2 years, we found that T-cell immunophenotype and elevated serum lactate dehydrogenase (LDH) were independent prognostic factors for survival. Patients with advanced disease were identified as risk factors for relapsed or refractory gastrointestinal tract NHL. CONCLUSIONS: In our subgroup survival analysis, we found that the survival outcomes demonstrated no significant differences between the stomach and intestinal tract NHL. Serum LDH levels and histologic subtypes were independent prognostic factors for the survival of gastrointestinal tract NHL. Advanced diseases were considered risk factors for relapsed or refractory gastrointestinal tract NHL.

Single-cell atlas of the immune microenvironment reveals macrophage reprogramming and the potential dual macrophage-targeted strategy in multiple myeloma.

The tumour microenvironment (TME) plays a critical role in disease progression in multiple myeloma (MM). This study aimed to present an atlas of MM-TME in disease progression and explore TME-directed therapeutic strategies. We performed single-cell RNA sequencing (scRNAseq) in samples from different disease stages. We validated the findings by bulk RNAseq, flow cytometry (FCM) and in vitro and in vivo functional experiments. We delineated a compromised TME during disease progression, characterized by enrichment of exhausted NK cells and CD8+ T cells and reprogramming of macrophages (MPs). The reprogrammed tumour-associated MPs (TAMs) displayed a mixed phenotype showing both M1 and M2 features, with two TAM clusters exclusively present in the MM stage showing higher M2 scores. We validated the mixed M1/M2 phenotype in TAMs in a clinical cohort and verified phagocytic dysfunction in reprogrammed TAMs. Cellular interaction analysis identified two enriched ligand-receptor pairs between MPs and malignant plasma cells (PCs), including the SIRPA-CD47 pathway suppressing phagocytosis and the CD74-MIF (macrophage inhibitory factor) reshaping the phenotype of MPs. The expression of CD47 and MIF correlated with disease progression and adverse outcomes. We designed a dual-MP-targeted strategy by combining an anti-CD47 antibody and MIF inhibitor to activate phagocytosis and repolarize MP to a functional phenotype and proved its potent antitumour effect in vitro and in vivo. We drafted alterations in MM-TME during disease progression and unravelled TAM's reprogramming. The dual MP-targeted approach blocking both CD47 and MIF showed potent antitumour effects.

multiMiAT: an optimal microbiome-based association test for multicategory phenotypes.

Microbes can affect the metabolism and immunity of human body incessantly, and the dysbiosis of human microbiome drives not only the occurrence but also the progression of disease (i.e. multiple statuses of disease). Recently, microbiome-based association tests have been widely developed to detect the association between the microbiome and host phenotype. However, the existing methods have not achieved satisfactory performance in testing the association between the microbiome and ordinal/nominal multicategory phenotypes (e.g. disease severity and tumor subtype). In this paper, we propose an optimal microbiome-based association test for multicategory phenotypes, namely, multiMiAT. Specifically, under the multinomial logit model framework, we first introduce a microbiome regression-based kernel association test for multicategory phenotypes (multiMiRKAT). As a data-driven optimal test, multiMiAT then integrates multiMiRKAT, score test and MiRKAT-MC to maintain excellent performance in diverse association patterns. Massive simulation experiments prove the success of our method. Furthermore, multiMiAT is also applied to real microbiome data experiments to detect the association between the gut microbiome and clinical statuses of colorectal cancer as well as for diverse statuses of Clostridium difficile infections.

Deciphering complex antibiotic resistance patterns in Helicobacter pylori through whole genome sequencing and machine learning.

Introduction: Helicobacter pylori (H.pylori, Hp) affects billions of people worldwide. However, the emerging resistance of Hp to antibiotics challenges the effectiveness of current treatments. Investigating the genotype-phenotype connection for Hp using next-generation sequencing could enhance our understanding of this resistance. Methods: In this study, we analyzed 52 Hp strains collected from various hospitals. The susceptibility of these strains to five antibiotics was assessed using the agar dilution assay. Whole-genome sequencing was then performed to screen the antimicrobial resistance (AMR) genotypes of these Hp strains. To model the relationship between drug resistance and genotype, we employed univariate statistical tests, unsupervised machine learning, and supervised machine learning techniques, including the development of support vector machine models. Results: Our models for predicting Amoxicillin resistance demonstrated 66% sensitivity and 100% specificity, while those for Clarithromycin resistance showed 100% sensitivity and 100% specificity. These results outperformed the known resistance sites for Amoxicillin (A1834G) and Clarithromycin (A2147), which had sensitivities of 22.2% and 87%, and specificities of 100% and 96%, respectively. Discussion: Our study demonstrates that predictive modeling using supervised learning algorithms with feature selection can yield diagnostic models with higher predictive power compared to models relying on single single-nucleotide polymorphism (SNP) sites. This approach significantly contributes to enhancing the precision and effectiveness of antibiotic treatment strategies for Hp infections. The application of whole-genome sequencing for Hp presents a promising pathway for advancing personalized medicine in this context.

[Birth weights of singleton neonates of 14 Chinese ethnic groups in 11 cities of China]. / 中国11市14ä¸ªæ°‘æ—å•èƒŽå„¿å‡ºç”Ÿä½“é‡ç ”ç©¶.

OBJECTIVES: To develop the birth weight curves of the Chinese Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, as well as the birth weight means of full-term neonates of 14 Chinese ethnic groups. METHODS: The live singleton neonates who were born in 11 maternal and child health care hospitals from 11 cities of China between January 2017 and December 2020 were classified according to the mother's ethnic group. Birth weight means were calculated for the full-term neonates of each ethnic group. For the Han and Zhuang singleton neonates with a large sample size, the Lambda-Mu-Sigma (LMS) method was used to establish the birth weight percentile curves of the Han and Zhuang singleton neonates with different gestational ages. RESULTS: A total of 105 365 live singleton neonates were included, among whom the Han neonates had the highest number of 84 851 (26-41 weeks of gestation), followed by the Zhuang neonates (12 803 neonates with a gestational age of 28-41 weeks). The neonates of the other Chinese ethnic groups enrolled were live full-term singleton neonates, with a sample size of more than 100 neonates for each ethnic group. The 3rd-97th percentile curves of birth weight were established for the Han singleton neonates with a gestational age of 26-41 weeks and the Zhuang singleton neonates with a gestational age of 28-41 weeks. The birth weight curves of the Han singleton neonates at each gestational age were higher than those of the Zhuang singleton neonates. Birth weight means (3 199-3 499 g) and standard deviations were determined for 14 Chinese ethnic groups, i.e., Li, Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups. The Li ethnic group had the lowest birth weight, followed by the Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups. CONCLUSIONS: The 3rd-97th percentile curves of birth weight are developed for the Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, and birth weight means are determined for the full-term neonates of 14 Chinese ethnic groups in 11 cities of China, which provides a reference for evaluating the intrauterine growth of neonates in these ethnic groups.

Arterial blood gas analysis aids early differential diagnosis and treatment of primary and secondary hypokalaemic periodic paralysis.

This study aimed to examine changes in electrolytes and acid-base status in primary and secondary hypokalaemic periodic paralysis (HypoPP), which will help early differential diagnosis of HypoPP. A total of 64 HypoPP patients were enrolled and relevant data from clinical records was collected. Overall, 64 patients (mean age 28.2±7.3 years) of which 58(91%) were males, with 39, 11 and 14 patients, respectively, diagnosed as primary HypoPP, thyrotoxic HypoPP, and other secondary HypoPPs at discharge, were assessed. Those with HypoPP secondary to conditions other than hyperthyroidism were more likely to develop acid-base imbalance (p<0.001); they had higher pH (p=0.046) and HCO3 levels (p=0.014) at baseline, and needed a higher dose of potassium supplement before the serum potassium level returned to normal (p=0.007) and a longer time to regain full muscle strength (p=0.004), compared with those with primary or thyrotoxic HypoPP. Emergent arterial blood gas analysis may aid early differential diagnosis of patients with primary and secondary HypoPP.