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Abstract In the KEYNOTE-811 study, anti-HER2 and immunotherapy treatments resulted in longer survival in HER2-positive gastric cancer patients with CPS ≥ 1, whereas CPS

Abstract Background It is well-established that thrombus aspiration during primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) indicates a higher thrombus burden and necessitates more intensive antithrombotic therapy. The bidirectional association between adverse events in AMI patients and platelet reactivity is typically observed during dual antiplatelet therapy (DAPT). Objective To investigate platelet reactivity after DAPT in AMI patients with thrombus aspiration performed during PCI. Methods In this retrospective study, we examined 269 consecutive AMI patients who underwent PCI and recorded their demographic, clinical and laboratory data. The platelet reactivity was measured with thromboelastogram (TEM). Results Ultimately, 208 patients were included in this study and divided into a Thrombus Aspiration group (N = 97) and a PCI Alone group (N = 111) based on whether thrombus aspiration was performed or not. The adenosine diphosphate (ADP)-induced platelet inhibition rate in the Thrombus Aspiration group was higher than that in the PCI Alone group (P

Abstract The de novo construction of enantioenriched 3-hydroxyindolenines and 3-oxindoles from easily available starting materials has been highly desired. Herein, an enantioselectively intermolecular direct [3 + 2] annulation of aryl amine with 2,3-diketoesters to construct 3-hydroxyindolenines with a chiral tertiary alcohol has been disclosed. The results of control experiments and DFT calculation revealed that π − π interaction plays a pivotal role in the enantioselectivity-determining process of [3 + 2] annulation. The following unusual concerted [1,2]-ester migration provides a family of chiral 3-oxindoles in good to excellent yields with excellent enantioselectivity.

In order to explore the effects of drying methods on the physicochemical properties and structure of Phyllostachys pubescens shoot powder (PPSP), this research used bamboo shoots as raw materials, and used spray drying (SD), hot air drying (HAD) and low-temperature vacuum drying (LVD) to get 3 kinds of PPSP. The nutrient content, water holding capacity, oil holding capacity, swelling capacity, color, and other physicochemical properties of samples were compared, and their structures were analyzed by infrared spectroscopy, X-ray diffraction and scanning electron microscopy. The results showed that the nutritional characteristics of PPSP prepared by different drying methods were significantly different（PLVD>HAD. The L*, a* and b* value of PPSP in the three groups were significantly different in color. The L* value of LVD sample was 77.32, which was significantly higher than that of SD and HAD samples (P

o uncover the regulatory metabolism of poly-glutamic acid (PGA) in protecting wheat crops against salt stress (SS) at the physiological level, we utilised hydroponic experiments to explore the roles of PGA in regulating the photosynthetic performance, water physiology, antioxidant metabolism and ion homeostasis of wheat seedlings exposed to SS for 10 days. The findings demonstrated that SS inhibited the photosynthetic performance of wheat seedlings. In contrast, different doses of PGA all improved the photosynthetic performance, especially for 0.3% PGA. Compared with SS, 0.3% PGA plus SS decreased nonphotochemical quenching (qN) by 26.3% and respectively increased photosynthetic rate (Pn), soil and plant analyser development (SPAD) value, maximum photochemical efficiency of photosystem II (PSII) (Fv/Fm), photochemical quenching (qP) and actual photochemical efficiency of PSII (Y(II)) by 54.0, 27.8, 34.6, 42.4 and 25.8%. For water metabolism, SS destroyed the water balance of wheat seedlings. In contrast, different doses of PGA enhanced water balance, especially for 0.3% PGA. Compared with SS, 0.3% PGA plus SS decreased leaf water saturation deficit (LWSD) by 35.5% and respectively increased leaf relative water content (LRWC), transpiration rate (Tr), stomatal conductance (gs) and the contents of soluble sugars (SSS) and proline (Pro) by 15.9, 94.7, 37.5, 44.6 and 62.3%. For antioxidant metabolism, SS induced the peroxide damage to wheat seedlings. In contrast, different doses of PGA all mitigated the SS-induced peroxide damage, especially for 0.3% PGA. Compared with SS, 0.3% PGA plus SS respectively decreased superoxide anion (O2-), hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents and electrolyte leakage (EL) by 39.1, 29.6, 46.2 and 36.3%, and respectively increased superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR), dehydroascorbate reductases (DHAR) and monodehydroascorbate reductase (MDHAR) activities, and antioxidants ascorbic acid (AsA) and glutathione (GSH) contents by 69.2, 49.2, 77.8, 80.6, 109.5, 121.7, 104.5, 63.8 and 39.6%. Besides, SS destroyed the ion homeostasis of wheat seedlings. In contrast, different doses of PGA all maintained ion homeostasis, especially for 0.3% PGA. Compared with SS, 0.3% PGA plus SS reduced Na+ content by 40.7% and respectively increased K+, Ca2+ and Mg2+ contents by 64.4, 82.6 and 105.6%, thereby respectively increasing K+/Na+, Ca2+/Na+ and Mg2+/Na+ ratios by 177.6, 209.4 and 244.8%. In the above ways, SS inhibited wheat height and biomass. In contrast, different doses of PGA all improved wheat height and biomass under SS, especially for 0.3% PGA. Compared with SS, 0.3% PGA plus SS, respectively, increased wheat height and biomass by 27.4% and 41.7%. In the above ways, PGA mitigated salt toxicity in wheat seedlings. The current findings implied that there was a potential for the use of PGA in real situations to improve wheat salt tolerance, especially for the 0.3% dose.

Abstract Background Aging is a prominent risk factor for diverse diseases; therefore, an in-depth understanding of its physiological mechanisms is required. Nonhuman primates, which share the closest genetic relationship with humans, serve as an ideal model for exploring the complex aging process. However, the potential of the nonhuman primate animal model in the screening of human aging markers is still not fully exploited. Multiomics analysis of nonhuman primate peripheral blood offers a promising approach to evaluate new therapies and biomarkers. This study explores aging-related biomarker through multilayer omics, including transcriptomics (mRNA, lncRNA, and circRNA) and proteomics (serum and serum-derived exosomes) in rhesus monkeys (Macaca mulatta). Results Our findings reveal that, unlike mRNAs and circRNAs, highly expressed lncRNAs are abundant during the key aging period and are associated with cancer pathways. Comparative analysis highlighted exosomal proteins contain more types of proteins than serum proteins, indicating that serum-derived exosomes primarily regulate aging through metabolic pathways. Finally, eight candidate aging biomarkers were identified, which may serve as blood-based indicators for detecting age-related brain changes. Conclusions Our results provide a comprehensive understanding of nonhuman primate blood transcriptomes and proteomes, offering novel insights into the aging mechanisms for preventing or treating age-related diseases.

Abstract Morchella spongiola is a highly prized mushroom for its delicious flavor and medical value and is one of the most flourishing, representative, and dominant macrofungi in the Qilian Mountains of the Qinghai-Tibet Plateau subkingdoms (QTPs). However, the understanding of M. spongiola remains largely unknown, and its taxonomy is ambiguous. In this study, we redescribed a unique species of M. spongiola, i.e., micromorphology, molecular data, genomics, and comparative genomics, and the historical biogeography of M. spongiola were estimated for 182 single-copy homologous genes. A high-quality chromosome-level reference genome of M. spongiola M12-10 was obtained by combining PacBio HiFi data and Illumina sequencing technologies; it was approximately 57.1 Mb (contig N50 of 18.14 Mb) and contained 9775 protein-coding genes. Comparative genome analysis revealed considerable conservation and unique characteristics between M. spongiola M12-10 and 32 other Morchella species. Molecular phylogenetic analysis indicated that M. spongiola M12-10 is similar to the M. prava/Mes-7 present in sandy soil near rivers, differentiating from black morels ~ 43.06 Mya (million years ago), and diverged from M. parva/Mes-7 at approximately 12.85 Mya (in the Miocene epoch), which is closely related to the geological activities in the QTPs (in the Neogene). Therefore, M. spongiola is a unique species rather than a synonym of M. vulgaris/Mes-5, which has a distinctive grey-brown sponge-like ascomata. This genome of M. spongiola M12-10 is the first published genome sequence of the species in the genus Morchella from the QTPs, which could aid future studies on functional gene identification, germplasm resource management, and molecular breeding efforts, as well as evolutionary studies on the Morchella taxon in the QTPs.

The influence of grain boundary segregation on corrosion behaviour of AA5083 alloy remains unclear. In the present work, the segregation in both as-received and sensitized AA5083 alloys was examined via transmission electron microscopy (TEM). The influence of TEM specimen preparation methods on grain boundary segregation detection was explored. It is revealed that focussed ion beam (FIB) is reliable for the detection of grain boundary segregation. Further, the influence of grain boundary segregation on intergranular corrosion (IGC) of AA5083 alloy was examined. It is indicated that Mg segregation at grain boundary is decisive for IGC development in AA5083-H116 alloy, which also benefits IGC development in sensitized AA5083-H116 alloy by increasing the continuity of grain boundary micro-chemistry.

Environmental sediments mainly consisting of CaO–MgO–Al2O3–SiO2 (CMAS) corrosion are a serious threat to thermal barrier coatings (TBCs), in which Fe element is usually ignored. Gd2Zr2O7 TBCs are famous for their excellent CMAS resistance. In this study, the characteristics of Fe-containing environmental sediments (CMAS-Fe) and their corrosiveness to Gd2Zr2O7 coatings were investigated. Four types of CMAS-Fe glass with different Fe contents were fabricated. Their melting points were measured to be 1322–1344 ℃, and the high-temperature viscosity showed a decreasing trend with increasing Fe contents. The corrosion behavior of four types of CMAS-Fe to Gd2Zr2O7 coatings at 1350 ℃ was investigated. At the initial corrosion stage (0.1 h), anorthite was precipitated in CMAS-Fe with a high Ca : Si ratio, while Fe-garnet was formed in the melt with the highest Fe content. Prolonging the corrosion time resulted in the formation of a reaction layer, which exhibited an interpenetrating network composed of Gd-oxyapatite, ZrO2, and residual CMAS-Fe. Some spinel was precipitated within the reaction layer. After 1 h or even longer time, the reaction layers tended to be stable and compact, which had comparable hardness and fracture toughness to those of Gd2Zr2O7 coatings. Under the cyclic CMAS-Fe attack, the residual CMAS-Fe in the interpenetrating network provided a pathway for the redeposited CMAS-Fe infiltration, resulting in the continuous growth of the reaction layer. As a result, the Gd2Zr2O7 coatings had a large consumption in the thickness, degrading the coating performance. Therefore, the Gd2Zr2O7 coatings exhibit unsatisfactory corrosion resistance to CMAS-Fe attack.

Extensive research has been conducted to investigate the impact of capsaicin (CAP) on lipid metabolism, focusing specifically on its interaction with the vanilloid subtype 1 (TRPV1) ion channel. Additionally, studies have illuminated the role of Akkermansia muciniphila (A. muciniphila), a specific strain of intestinal microbiota, in lipid metabolism. In this study, a model utilizing resiniferatoxin (RTX) was employed to deactivate TRPV1 ion channels in germ-free mice, followed by the administration of A. muciniphila via gavage. Following the collection of intestinal tissues for a comprehensive analysis, employing histopathology, qPCR, and ELISA techniques, our findings revealed a significant upregulation of MUC2 and MUC3 expression induced by CAP. This upregulation resulted in the thickening of the colonic mucus layers. Notably, this effect was absent when TRPV1 was selectively inhibited. Moreover, there was no discernible impact on goblet cells. The findings strongly indicate that CAP influences the system by activating the TRPV1 ion channel, thereby enhancing the expression of mucin MUC2 and promoting an augmentation in the thickness of the mucous layer. This activation, in turn, supplies A. muciniphila with an ample source of carbon and nitrogen. This insight potentially clarify the underlying mechanism through which CAP facilitates the increase in A. muciniphila abundance.

Abstract Contrast-induced acute kidney injury (CI-AKI) has become the third leading cause of hospital-acquired AKI, which seriously threatens the health of patients. To date, the precise pathogenesis of CI-AKI has remained not clear and may be related to the direct cytotoxicity, hypoxia and ischemia of medulla, and oxidative stress caused by iodine contrast medium, which have diverse physicochemical properties, including cytotoxicity, permeability and viscosity. The latest research shows that microRNAs (miRNAs) are also involved in apoptosis, pyroptosis, and autophagy which caused by iodine contrast medium (ICM), which may be implicated in the pathogenesis of CI-AKI. Unfortunately, effective therapy of CI-AKI is very limited at present. Therefore, effective prevention of CI-AKI is of great significance, and several preventive options, including hydration, antagonistic vasoconstriction, and antioxidant drugs, have been developed. Here, we review current knowledge about the features of iodine contrast medium, the definition, pathogenesis, molecular mechanism, risk factors, prevention and treatment of CI-AKI.

BackgroundThe majority of patients with lung cancer exhibit drug resistance after anti-PD-1 immunotherapy, leading to shortened patient survival time. Previous studies have suggested an association between epigenetic abnormalities such as methylation and clinical response to anti-PD-1 immunotherapy, while the role of SUMOylation in resistance to anti-PD-1 antibody immunotherapy is still unclear.MethodsHere, the mRNA expression of 15 SUMO machinery components in PBMC from lung cancer patients receiving anti-PD-1 immunotherapy were analyzed using real-time PCR. Base on the percentage change in mRNA levels, the relationship between the expression of SUMO machinery components and outcomes of anti-PD-1 immunotherapy, and the influencing factors of SUMOylation were evaluated. PBMC was treated with different concentrations of 2-D08 (a specific inhibitor of SUMOylation) in vitro, and analyzed the activation and the death rates of lymphocyte subsets by flow cytometry analysis.ResultsA predictive method, base on the gene expression of three SUMO machinery components (SUMO1, SUMO3 and UBE2I), were developed to distinguish non-responders to PD-1 inhibitors. Furthermore, the number of lymphocytes in peripheral blood significantly reduced in the dysregulated SUMOylation groups (the percentage change >100 or -50 ~ -100 groups). In vitro studies confirmed that lightly low SUMOylation level improved the activation status of T and NK lymphocytes, but extremely low SUMOylation level lead to the increased death rates of lymphocytes.ConclusionOur findings implied that dysregulated gene expression of SUMO machinery components could induce the resistance of anti-PD-1 immunotherapy in lung cancer by upregulating the death of peripheral blood lymphocytes. These data might provide effective circulating biomarkers for predicting the efficacy of anti-PD-1 immunotherapy, and uncovered a novel regulatory mechanism of resistance to anti-PD-1 immunotherapy.

BackgroundEfgartigimod (Efgartigimod alpha fcab, Vyvgart™) is a pioneering neonatal Fc receptor (FcRn) antagonist for the treatment of severe autoimmune diseases mediated by pathogenic immunoglobulin G (IgG) autoantibodies, including myasthenia gravis (MG). It is a well-tolerated drug with minor side effects, such as headache and upper respiratory (lung) and urinary tract infections. Here, we present a case of Kaposi’s varicelliform eruption (KVE) and herpetic conjunctivitis related to efgartigimod in a 60-year-old patient with ocular MG (OMG).Case descriptionA 60-year-old Chinese male suffered from acetylcholine receptor antibody positive (AChR Ab+) OMG for 8 years. During this period, he underwent first-line treatment with systemic corticosteroids, cyclosporine, cyclophosphamide, and so on, but had poor symptom improvement. On the recommendation of his attending neurologist, he received one cycle of intravenous efgartigimod (10mg/kg, once weekly for 4 weeks). The patient experienced fever, widespread painful blisters, and edema on the face on the third day after his last intravenous infusion. The patient also complained of increased secretions and a foreign body sensation in both eyes. Laboratory tests confirmed infection with herpes simplex virus (HSV). A diagnosis of efgartigimod-associated KVE and herpetic conjunctivitis was made. After intravenous administration (5mg/kg, 3 times a day, every 8 hours) for 10 days, the patient was cured without residual complications.ConclusionsThis case is the first report of a patient with KVE and herpetic conjunctivitis related to efgartigimod in PubMed. This is rare and unusual. Clinicians should be alert to the rare symptoms related to efgartigimod.

Abstract Background Glucagon‐like peptide 1 receptor agonists have been shown to reduce all‐cause and cardiovascular mortality in patients with Type 2 diabetes mellitus (T2DM). The probable increase in heart rate hinders its early usage in acute myocardial infarction patients. In our study, we aimed to find out whether the use of liraglutide in patients with acute myocardial infarction as early as at the time of hospitalization would increase the heart rate. Methods This was an observational retrospective study. From December 2020 to August 2021, 200 patients with acute myocardial infarction were included in our study and divided into three groups: T2DM + liraglutide group (n = 46), T2DM + non‐liraglutide group (n = 42), and non‐T2DM group (n = 112). The primary outcomes were the differences in heart rate. Secondary outcomes were differences in systolic and diastolic blood pressure. Results There were no significant differences in heart rate among the three groups at admission, the day before the first shot of liraglutide, and before discharge. There was also no significant difference in heart rate between diabetic patients with acute myocardial infarction and those on liraglutide during the hospital stay. And there were no differences of beta‐blocker dosages among the three groups. Liraglutide did not affect the blood pressure during acute myocardial infarction. Conclusions Liraglutide did not increase the heart rate in diabetic patients during acute myocardial infarction and did not lead to an increase in the dose of beta‐blockers in the patients. It also had no effect on blood pressure and showed better efficacy in lowering glucose levels without additional hypoglycemic events.

An experimental investigation was performed to study the seismic performance of columns enhanced by the 630 MPa high-strength steel bars (HSSBs) and ultra-high-performance fiber reinforced concrete (UHPFRC). Six HSSBs-UHPFRC enhanced columns and one normal concrete (NC) column reinforced with the HSSBs were subjected to static cyclic lateral loading. The effects of steel fiber volume ratio, axial compression ratio, longitudinal reinforcement ratio, and stirrup spacing on the seismic performance of UHPFRC columns were studied, and the differences in seismic performance between UHPFRC columns and NC column were compared and analyzed. The test results indicated that the UHPFRC columns exhibited superior flexural ductile failure with excellent integrity compared to the NC column, and the height of the damaged area was much smaller than that of the NC column. The tensile and compressive properties of the 630 MPa high-strength steel bars could be fully utilized in the UHPFRC columns, which had a good match with UHPFRC. The HSSBs-UHPFRC columns exhibited satisfactory bearing capacity, adequate ductility, and large energy dissipation capacity. Furthermore, the bearing capacity degradation of all specimens was greater than 0.85, indicating that the HSSBs-UHPFRC columns possessed robust bearing capacity stability. A higher volume ratio of steel fiber or denser stirrup spacing could effectively restrain UHPFRC and longitudinal reinforcement bars to enhance the ductility of the specimens. With the longitudinal reinforcement ratio increasing, the superior mechanical properties of the HSSBs and UHPFRC could be utilized better in the UHPFRC column and the seismic performance and flexural capacity of the UHPFRC specimen could also be enhanced correspondingly. A formula to calculate the flexural capacity of the HSSBs-UHPFRC columns was established based on the analysis of the specimens' flexural capacity. The calculated values were found to agree with the experimental values well. The results can serve as a reference for designing HSSBs-UHPFRC enhanced structures．

Abstract To assess the skiing economy (SE) and kinematics during double poling (DP) roller skiing between two groups of skiers in a field setting. Five experienced and five novice male skiers performed a SEDP test at 16 km∙h−1 on an outdoor athletics track. Gas exchange parameters were measured to determine SEDP. A two-dimensional video was filmed to measure the kinematics variables. Experienced skiers exhibited a 21% lower oxygen cost than novice skiers (p = 0.016) in DP, indicating a strong association between SEDP, cycle length and cycle rate (p

Abstract Massive increases in the risks of depressive disorders and the ensuing suicide have become the overarching menace for children/adolescents. Despite global consensus to instigate psychological healthcare policy for these children/adolescents, their effects remain largely unclear neither from a small amount of official data nor from small-scale scientific studies. More importantly, in underprivileged children/adolescents in lower-middle-economic-status countries/areas, the data collection may not be as equally accessible as in developed countries/areas, thus resulting in underrepresented observations. To address these challenges, we released a large-scale and multi-center cohort dataset (n = 249,772) showing the effects of primary psychological healthcare on decreasing depression and suicidal ideation in these children/adolescents who were underrepresented in previous studies or current healthcare systems, including unattended children/adolescents, orphans, children/adolescents in especially difficult circumstances, and “left-behind” and “single-parenting” children/adolescents. We provided all individual data recording the depressive symptoms and suicide ideation that had been collected at baseline (Oct 2022) and half-year follow-up (May 2023) from practicing this psychological healthcare system.

Abstract Thyroid carcinoma (THCA) is the most common endocrine cancer. Phosphodiesterase (PDE) 4 enzyme family, as specific regulator of cyclic adenosine monophosphate, may play a important role in THCA. However, few studies on PDE4 enzyme family in THCA have been reported yet. Therefore, this study aimed to systematically analyze the changes of PDE4 enzyme family in THCA, and look for potential target for THCA therapy. We systematically analyzed the expression differences, prognostic value, genetic alteration, methylation modification, and the correlation with tumor immune microenvironment of PDE4 family in THCA using several public databases, including TCGA, GEO, GSCA, TNMplot, cBioPortal, DiseaseMeth and TIMER. Besides, functional enrichment analysis and protein–protein interaction (PPI) network of PDE4 family was investigated using Metascape and STRING databases. The expression levels of PDE4A, PDE4B and PDE4D were down-regulated in THCA patients at different cancer stages, while the expression level of PDE4C was significantly up-regulated. Moreover, THCA patients with higher PDE4C expression had shorter progress free survival compared with those with lower PDE4C expression. The low genomic alteration frequencies and mildly increased methylation levels of PDE4 family were found in THCA patients. Except for PDE4A, the expression levels of PDE4B, PDE4C and PDE4D could affect many immune cells infiltration during THCA progression. Four PDE4 subtypes were all enriched in cAMP catabolic process. Nevertheless, PDE4C was not enriched in the cAMP binding signal pathway, and PDE4B was not enriched in the G alphas signaling events. Notably, PDE4C participated in cAMP metabolic process by regulating adenylate cyclases (ADCYs), which involved ADCY1, ADCY5, ADCY6, ADCY8 and ADCY9. The findings of this study provide a partial basis for the role of PDE4 family in the occurrence and development of THCA. In addition, this study also suggested that PDE4C might be a potential prognostic marker of THCA, which could serve as a reference for future basic and clinical research.

Abstract In two-dimensional chiral metal-halide perovskites, chiral organic spacers endow structural and optical chirality to the metal-halide sublattice, enabling exquisite control of light, charge, and electron spin. The chiroptical properties of metal-halide perovskites have been measured by transmissive circular dichroism spectroscopy, which necessitates thin-film samples. Here, by developing a reflection-based approach, we characterize the intrinsic, circular polarization-dependent complex refractive index for a prototypical two-dimensional chiral lead-bromide perovskite and report large circular dichroism for single crystals. Comparison with ab initio theory reveals the large circular dichroism arises from the inorganic sublattice rather than the chiral ligand and is an excitonic phenomenon driven by electron-hole exchange interactions, which breaks the degeneracy of transitions between Rashba-Dresselhaus-split bands, resulting in a Cotton effect. Our study suggests that previous data for spin-coated films largely underestimate the optical chirality and provides quantitative insights into the intrinsic optical properties of chiral perovskites for chiroptical and spintronic applications.

Abstract Consumer participation is critical to achieving successful food safety governance. However, in the field of food safety governance, consumer participation faces the dilemma of collective action. Based on social capital theory, this study introduces a total of 1229 questionnaires from online food consumers in China were collected by randomly distributing electronic questionnaires to online shoppers, and tests the effect and mechanism of social capital on consumer participation in food safety governance. By using ordered regression and multinomial logit models, the empirical results show that social capital can reduce the adverse effects of free-riding on consumers’ participation in food safety governance and in fact will ultimately encourage consumers to participate in food safety governance. Furthermore, social capital will enhance people’s participation in food safety governance through two paths: promoting consumers’ sharing of food safety information and promoting consumers’ direct supply of safe food. The conclusion of this paper provides inspiration for the promotion of consumer participation in the public affairs related to food safety governance in developing countries.

Abstract Hemorrhagic toxin (TcsH) is a major virulence factor produced by Paeniclostridium sordellii, which is a non-negligible threat to women undergoing childbirth or abortions. Recently, Transmembrane Serine Protease 2 (TMPRSS2) was identified as a host receptor of TcsH. Here, we show the cryo-EM structures of the TcsH-TMPRSS2 complex and uncover that TcsH binds to the serine protease domain (SPD) of TMPRSS2 through the CROP unit-VI. This receptor binding mode is unique among LCTs. Five top surface loops of TMPRSS2SPD, which also determine the protease substrate specificity, constitute the structural determinants recognized by TcsH. The binding of TcsH inhibits the proteolytic activity of TMPRSS2, whereas its implication in disease manifestations remains unclear. We further show that mutations selectively disrupting TMPRSS2-binding reduce TcsH toxicity in the intestinal epithelium of the female mice. These findings together shed light on the distinct molecular basis of TcsH-TMPRSS2 interactions, which expands our knowledge of host recognition mechanisms employed by LCTs and provides novel targets for developing therapeutics against P. sordellii infections.

Objectives: Clostridium perfringens (C. perfringens) is a significant opportunistic pathogen. This study aims to examine the occurrence of C. perfringens in patients with diarrhoea and food poisoning and compare the genetic similarities with strains found in poultry retail markets and poultry farms in the same city (Tai'an, China). Methods: Clostridium perfringens was isolated from 30 human faecal samples and genotyped using multiplex PCR. The antimicrobial susceptibility test was conducted using the Kirby-Bauer disk diffusion method. Genetic relationships were analysed through Multi-locus sequence typing (MLST) and Phylogenetic analysis. Results: The positive rate of C. perfringens was found to be 96.67%. Among the positive samples, 91.67% of the faecal samples from patients with food poisoning contained type F strains of C. perfringens, while only 16.67% of the samples from diarrhoea cases contained type F. The drug susceptibility test revealed that the majority of isolates displayed broad-spectrum antimicrobial resistance. Out of the 57 isolates tested for drug susceptibility, 89.47% demonstrated resistance to at least three antibiotics. The MLST results indicated that strains originating from the same host and environment tended to be more closely related. However, certain strains associated with food poisoning and diarrhoea in patients shared the same ST and CC as some strains found in the retail market. These strains were also found to be phylogenetically similar to some retail market strains, suggesting potential risks to human health. Conclusions: Therefore, it is crucial to enhance the management of poultry retail markets in order to mitigate these associated risks.

Let $ \mathbb{F}_q $ be the finite field of order $ q $ where $ q = p^{k} $, $ k $ is a positive integer and $ p $ is an odd prime. Let $ \mathbb{F}_q^* $ represent the nonzero elements of $ \mathbb{F}_{q} $. For $ f(x_1, \cdots, x_n)\in\mathbb{F}_q[x_1, \cdots, x_n] $, we used $ N\big(f(x_1, \cdots, x_n) = 0\big) $ to denote the number of $ \mathbb{F}_q $-rational points of the affine hypersurface $ f(x_1, \cdots, x_n) = 0 $. In 2020, Zhao et al. obtained the explicit formulae for $ N(x_1^4+x_2^4 = c) $, $ N(x_1^4+x_2^4+x_3^4 = c) $ and $ N(x_1^4+x_2^4+x_3^4+x_4^4 = c) $ over $ \mathbb{F}_q $, with $ c\in\mathbb{F}_q^* $. In this paper, by using Jacobi sums and an analog of the Hasse-Davenport theorem, we arrived at explicit formulae for $ N(a_1x_1^4+a_2x_2^4 = c) $ and $ N(b_1x_1^4+b_2x_2^4+b_3x_3^4 = c) $ with $ a_i, b_j\in \mathbb{F}_q^* (1\leq i \leq 2, 1 \leq j \leq 3) $ and $ c\in \mathbb{F}_q $. Furthermore, by using the reduction formula for Jacobi sums, the number of rational points of the quartic diagonal hypersurface $ a_1x_1^4+a_2x_2^4+\cdots+a_nx_n^4 = c $ of $ n\geq 4 $ variables with $ a_i\in\mathbb{F}_q^* $ $ (1\leq i\leq n) $, $ c\in\mathbb{F}_q $ and $ p\equiv1({\rm{mod}} \ 4) $, can also be deduced. These extended and improved earlier results.

Highlights Nanocomposite/hydrogel hybrid electrodes are created with high interfacial toughness by introducing soft microfoams as the mechanically interlocking layer. In the hybrid electrodes, silver nanowires and hydrogels are electrically connected through the porous microfoams, achieving high conductivity and low contact impedance for high-quality biopotential recordings. The microfoam-enabled bonding strategy is generally applicable to diverse polymer substrates.

Abstract Epidermal electronics is an emerging wearable platform that involves attaching deformable forms of devices to the skin. Epidermal electrodes represent a vital component of this technology, as they provide a direct electronic interface with the skin for sensing and stimulation. However, most of the current electrodes are built on non‐permeable elastomer substrates, which can limit their long‐term, continuous operations in a non‐invasive manner. Fortunately, recent advancements in conductive materials and fabrication techniques have enabled high‐performance epidermal electrodes that are comfortable to wear. In order to track the latest progress, this review article first introduces the designs of permeable structures and the preparation of conductive electrodes. The subsequent discussion elaborates on effective strategies to achieve desirable properties, such as high conductivity, stretchability, skin adhesion, and biocompatibility. The emerging applications of permeable epidermal electrodes are also summarized. Finally, this review concludes with the current challenges and future directions of breathable epidermal electrodes.

ObjectivePrevious research has shown that human identical sequences of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) promote coronavirus disease 2019 (COVID-19) progression by upregulating hyaluronic acid (HA). However, the association of HA with mortality and long COVID in SARS-CoV-2 reinfection and first infection is unclear.MethodsPatients with COVID-19 at Beijing Ditan Hospital from September 2023 to November 2023 were consecutively enrolled. SARS-CoV-2 reinfections were matched 1:2 with first infections using a nearest neighbor propensity score matching algorithm. We compared the hospital outcomes between patients with COVID-19 reinfection and first infection. The association between HA levels and mortality and long COVID in the matched cohort was analyzed.ResultsThe reinfection rate among COVID-19 hospitalized patients was 25.4% (62 cases). After propensity score matching, we found that reinfection was associated with a better clinical course and prognosis, including lower levels of C-reactive protein and erythrocyte sedimentation rate, fewer cases of bilateral lung infiltration and respiratory failure, and shorter viral clearance time and duration of symptoms (p 0.05).ConclusionSerum HA may serve as a novel biomarker for predicting COVID-19 mortality in patients with SARS-CoV-2 reinfection and first infection. However, HA levels may not be associated with long COVID.

ObjectiveInflammation contributes to the development of metabolic bone diseases. The C-reactive protein-to-albumin ratio (CAR) is an inflammation-based marker with a prognostic value for several metabolic diseases. This study investigated the relationship between the CAR and osteoporosis (OP) in patients with primary biliary cholangitis (PBC).MethodsPatients with PBC treated at Beijing Ditan Hospital between January 2018 and June 2023 were enrolled. Logistic regression analysis was performed to investigate the factors influencing OP. The predictive value of CAR for OP was evaluated using receiver operating characteristic (ROC) curves. Moreover, a restricted cubic spline (RCS) fitted with a logistic regression model was used to analyze the relationship between CAR and OP.ResultsThe prevalence of OP among the patients with PBC was 26.9% (n = 82). CAR levels were higher in the OP group than in the non-OP group (0.33 (0.09, 0.61) vs. 0.08 (0.04, 0.18), P < 0.001). Logistic regression analysis showed that CAR was an independent predictor of OP in patients with PBC (odds ratio = 2.642, 95% confidence interval = 1.537-4.540, P < 0.001). CAR exhibited a good predictive ability for OP, with an areas under the curve (AUC) of 0.741. We found that individuals with CAR values > 0.1 have higher odds of OP. In addition, high CAR levels were associated with an increased prevalence of fragility fractures and high 10-year fracture risk.ConclusionHigh CAR levels were associated with greater odds of developing OP, and the CAR could serve as an independent predictor of OP in patients with PBC.

Satellite global digital elevation models (GDEMs) suffer from positive biases in urban areas due to building artifacts. While various machine learning (ML)-based methods have been proposed to remove these biases, their generalizability is limited by spatial heterogeneity and redundancy in prediction factors across different regions. Therefore, to investigate the spatial heterogeneity of prediction factors and address the problem of factor redundancy in ML-based model prediction, this paper proposes an explainable artificial intelligence framework (XAI) for correcting urban GDEMs using the SHapley additive explanation (SHAP)-random forest (RF) algorithm. The performance of the proposed model for correcting the 30-m COPDEM (COPDEM30) was demonstrated in New York City. The results were compared with the first global Forests-And-Buildings removed DEM (FABDEM) and three classical RF-based models without considering spatial heterogeneity and (or) factor optimization. The results indicate that each factor contributes differently to the correction of COPDEM30 across the regions, showing distinct regional characteristics and spatial heterogeneity. The constructed model is more applicable to regions with similar features to the training regions. In comparison to the three traditional RF-based models in areas with training points, the proposed method obtains the high accuracy. Specifically, while the Root Mean Square Error (RMSE) and Mean Absolute Error (MAE) values of the classical RF models ranged between 2.601 m and 2.724 m, and 1.686 m and 1.785 m, respectively, the proposed method achieves an RMSE of 2.258 m and an MAE of 1.436 m. Moreover, the proposed method reduces the RMSE (MAE) of the original COPDEM30 from 7.652 m (4.858 m) to 3.797 m (2.404 m), when applied to an area without providing training points. In summary, the XAI framework based on SHAP-RF can effectively quantify the contribution of prediction factors on GDEM correction, both globally and locally, which is conducive to the construction and improvement of the prediction factor system for urban GDEM correction in different regions. It also provides a reference for improving the performance of ML-based spatial prediction in geosciences.

Abstract Paeniclostridium sordellii lethal toxin (TcsL) is a potent exotoxin that causes lethal toxic shock syndrome associated with fulminant bacterial infections. TcsL belongs to the large clostridial toxin (LCT) family. Here, we report that TcsL with varied lengths of combined repetitive oligopeptides (CROPs) deleted show increased autoproteolysis as well as higher cytotoxicity. We next present cryo-EM structures of full-length TcsL, at neutral (pH 7.4) and acidic (pH 5.0) conditions. The TcsL at neutral pH exhibits in the open conformation, which resembles reported TcdB structures. Low pH induces the conformational change of partial TcsL to the closed form. Two intracellular interfaces are observed in the closed conformation, which possibly locks the cysteine protease domain and hinders the binding of the host receptor. Our findings provide insights into the structure and function of TcsL and reveal mechanisms for CROPs-mediated modulation of autoproteolysis and cytotoxicity, which could be common across the LCT family.

Abstract Ustilago maydis is a pathogenic fungus in Basidiomycota causing corn smut disease. A strain of U. maydis YZZF202006 was isolated from the tumor of corn smut collected from Jingzhou city in China. The intracellular bacteria were confirmed inner hyphal of the strain YZZF202006 by PCR amplification and fluorescence in situ hybridization (FISH) and SYTO-9. An endohyphal bacterium YZUMF202001 was isolated from the protoplasts of the strain YZZF202006. It was gram-negative, short rod-shaped with smooth light yellow colony. The endohyphal bacterium was genomic evidenced as Klebsiella michiganensis on the basis of average nucleotide identity (ANI) analysis and the phylogram. Then K. michiganensis was GFP-Labeled and reintroduced into U. maydis, which confirmed the bacterium can live in hyphae of U.maydis. The bacterium can grow on N-free culture media. Its nitrogenase activity was reached av. 646.25 ± 38.61 nmol·mL− 1·h− 1 C2H4 by acetylene reduction assay. A cluster of nitrogen fixation genes (nifJHDKTXENXUSVWZMFLABQ) was found from its genome. The endohyphal K. michiganensis may play an important role to help nitrogen fixation for fungi in the future.

Abstract The breeding of crops with improved nitrogen use efficiency (NUE) is crucial for sustainable agriculture, but the involvement of epigenetic modifications remains unexplored. Here, we analyze the chromatin landscapes of two wheat cultivars (KN9204 and J411) that differ in NUE under varied nitrogen conditions. The expression of nitrogen metabolism genes is closely linked to variation in histone modification instead of differences in DNA sequence. Epigenetic modifications exhibit clear cultivar-specificity, which likely contributes to distinct agronomic traits. Additionally, low nitrogen (LN) induces H3K27ac and H3K27me3 to significantly enhance root growth in KN9204, while remarkably inducing NRT2 in J411. Evidence from histone deacetylase inhibitor treatment and transgenic plants with loss function of H3K27me3 methyltransferase shows that changes in epigenetic modifications could alter the strategy preference for root development or nitrogen uptake in response to LN. Here, we show the importance of epigenetic regulation in mediating cultivar-specific adaptation to LN in wheat.

The development of an effective method for predicting the transfer of biologics from plasma into breast milk is important to ensure the safe use of medications during lactation. The aim of this study was to develop a regression model that could predict the transfer of monoclonal antibodies (mAbs) and Fc-fusion proteins from plasma into breast milk. By searching various databases, a list of eleven mAbs and Fc-fusion proteins with available information of presence in the breast milk was generated. Physicochemical properties such as the isoelectric point (pI), molecular weight (MW), dissociation constant (Kd), and pharmacokinetic (PK) parameters such as clearance (CL), volume of distribution (Vd), and half-life (T1/2) were collected or calculated. A two-variable non-linear regression analysis and a multivariate regression analysis were employed to establish correlation of milk-to-plasma (M/P) ratios with different combinations of two physicochemical properties. The 3D isoelectric point (pI) of the Fv region and the buried surface area (BSA) between the light and heavy chains (LC_HC) were two factors that emerged as a promising predictor of the milk-to-plasma concentration ratio (M/P). The correlation between M/P ratio, 3D pI of Fv region, and BSA_LC_HC was found to be good with R2 of 0.9058. Other combinations of the physicochemical properties did not show a statistically significant correlation. The multivariate regression model was used to predict the MP ratios for 79 different mAbs. We believe that this regression model could serve as a valuable tool to estimate the M/P ratios of mAbs and Fc-fusion proteins. Further model validation is necessary when the M/P ratios of additional biologics are available. This could inform clinical decision-making and improve the safety of large molecule drug use during lactation.

To remove vegetation bias (VB) from the global DEMs (GDEMs), an artificial neural network (ANN)-based method with the consideration of elevation spatial autocorrelation is developed in this paper. Three study sites with different forest types (evergreen, mixed evergreen-deciduous, and deciduous) are employed to evaluate the performance of the proposed model on three popular 30-m GDEMs, including SRTM1, AW3D30, and COPDEM30. Taking LiDAR DTM as the ground truth, the accuracy of the GDEMs before and after VB correction is assessed, as well as two existing GDEMs including MERIT and FABDEM. Results show that all the original GDEMs significantly overestimate the LiDAR DTM in the three forest types, with the largest biases of 21.5 m for SRTM1, 26.3 m for AW3D30, and 27.18 m for COPDEM30. Taking data randomly sampled from the corrected area as the training points, the proposed model reduces the mean errors (root mean square errors) of the three GDEMs by 98.8%−99.9% (55.1%−75.8%) in the three forests. When training data have the same forest type as the corrected GDEM but under different local situations, the proposed model lowers the GDEM errors by at least 76.9% (44.1%). Furthermore, our corrected GDEMs consistently outperform the existing GDEMs for the two cases.

Abstract Background This study was undertaken to explore the predictive value of the advanced lung cancer inflammation index (ALI) combined with the geriatric nutritional risk index (GNRI) for all-cause mortality in patients with heart failure (HF). Methods and results We enrolled 1123 patients with HF admitted to our cardiology department from January 2017 to October 2021. Patients were divided into four groups, according to the median ALI and GNRI. From the analysis of the relationship between the ALI and GNRI, we concluded that there was a mild positive linear correlation (r = 0.348, p

A classical theorem of A. D. Alexandrov says that a connected compact smooth hypersurface in Euclidean space with constant mean curvature must be a sphere. We give exposition to some results on symmetry properties of hypersurfaces with ordered mean curvature and associated variations of the Hopf Lemma. Some open problems will be discussed.

Abstract Background Interrupted time series (ITS) analysis is a growing method for assessing intervention impacts on diseases. However, it remains unstudied how the COVID-19 outbreak impacts gonorrhea. This study aimed to evaluate the effect of COVID-19 on gonorrhea and predict gonorrhea epidemics using the ITS-autoregressive integrated moving average (ARIMA) model. Methods The number of gonorrhea cases reported in China from January 2005 to September 2022 was collected. Statistical descriptions were applied to indicate the overall epidemiological characteristics of the data, and then the ITS-ARIMA was established. Additionally, we compared the forecasting abilities of ITS-ARIMA with Bayesian structural time series (BSTS), and discussed the model selection process, transfer function, check model fitting, and interpretation of results. Result During 2005–2022, the total cases of gonorrhea were 2,165,048, with an annual average incidence rate of 8.99 per 100,000 people. The highest incidence rate was 14.2 per 100,000 people in 2005 and the lowest was 6.9 per 100,000 people in 2012. The optimal model was ARIMA (0,1, (1,3)) (0,1,1)12 (Akaike’s information criterion = 3293.93). When predicting the gonorrhea incidence, the mean absolute percentage error under the ARIMA (16.45%) was smaller than that under the BSTS (22.48%). The study found a 62.4% reduction in gonorrhea during the first-level response, a 46.47% reduction during the second-level response, and an increase of 3.6% during the third-level response. The final model estimated a step change of − 2171 (95% confidence interval [CI] − 3698 to − 644) cases and an impulse change of − 1359 (95% CI − 2381 to − 338) cases. Using the ITS-ARIMA to evaluate the effect of COVID-19 on gonorrhea, the gonorrhea incidence showed a temporary decline before rebounding to pre-COVID-19 levels in China. Conclusion ITS analysis is a valuable tool for gauging intervention effectiveness, providing flexibility in modelling various impacts. The ITS-ARIMA model can adeptly explain potential trends, autocorrelation, and seasonality. Gonorrhea, marked by periodicity and seasonality, exhibited a downward trend under the influence of COVID-19 intervention. The ITS-ARIMA outperformed the BSTS, offering superior predictive capabilities for the gonorrhea incidence trend in China.

Abstract Background Tumor regression grade (TRG) is a measure of histopathological response to neoadjuvant therapy (NAT). Post‐therapy lymph node (ypN) metastasis was reported as a prognostic factor. However, the evaluation of the treatment effectiveness of NAT has not been well studied. Here, we explored whether TRG combined with ypN status could be a prognostic factor for gastroesophageal junction (GEJ) and gastric cancer (GC). Besides, we aimed at making clear the association of different neoadjuvant regimens with different TRG and ypN status. Methods 376 patients with GEJ or GC accepting NAT in Peking University Cancer Hospital were retrospectively collected from January 1, 2003 to June 30, 2021. According to TRG and ypN status, patients were innovatively categorized into four groups: TRG0N0, TRG1‐3N0, TRG0‐1N+, and TRG2‐3N+. We applied Kaplan–Meier method and log‐rank test to testify the differences in disease free survival (DFS) and overall survival (OS) among four groups. Univariate and multivariate analyses were performed to examine the relationships between TRG combined with ypN status and prognosis. Results We observed significant survival differences among the four groups (p

Abstract Objective Hepatitis C presents a profound global health challenge. The impact of COVID-19 on hepatitis C, however, remain uncertain. This study aimed to ascertain the influence of COVID-19 on the hepatitis C epidemic trend in Henan Province. Methods We collated the number of monthly diagnosed cases in Henan Province from January 2013 to September 2022. Upon detailing the overarching epidemiological characteristics, the interrupted time series (ITS) analysis using autoregressive integrated moving average (ARIMA) models was employed to estimate the hepatitis C diagnosis rate pre and post the COVID-19 emergence. In addition, we also discussed the model selection process, test model fitting, and result interpretation. Results Between January 2013 and September 2022, a total of 267,968 hepatitis C cases were diagnosed. The yearly average diagnosis rate stood at 2.42/100,000 persons. While 2013 witnessed the peak diagnosis rate at 2.97/100,000 persons, 2020 reported the least at 1.7/100,000 persons. The monthly mean hepatitis C diagnosed numbers culminated in 2291 cases. The optimal ARIMA model chosen was ARIMA (0,1,1) (0,1,1)12 with AIC = 1459.58, AICc = 1460.19, and BIC = 1472.8; having coefficients MA1=-0.62 (t=-8.06, P

Abstract Background Immune cell heterogenicity is known to determine the therapeutic response to cancer progression. Neoadjuvant chemoimmunotherapy (NACI) has shown clinical benefits in some patients with advanced head and neck squamous cell carcinoma (HNSCC), but the underlying mechanism behind this clinical response is unknown. The efficacy of NACI needs to be potentiated by identifying accurate biomarkers to predict clinical responses. Here, we attempted to identify molecules predicting NACI response in advanced HNSCC. Methods We performed combined single‐cell RNA sequencing (scRNA‐seq) and multiplex immunofluorescence (mIHC) staining with tumor samples derived from NACI‐treated HNSCC patients to identify a new tumor‐infiltrating cell (TIL) subtype, CD103+CD8+ TILs, associated with clinical response, while both in vitro and in vivo assays were carried out to determine its antitumor efficiency. The regulatory mechanism of the CD103+CD8+ TILs population was examined by performing cell‐cell interaction analysis of the scRNA‐seq data and spatial analysis of the mIHC images. Results We established intratumoral CD103+CD8+ TILs density as a determinant of NACI efficacy in cancers. Our scRNA‐seq results indicated that the population of CD103+CD8+ TILs was dramatically increased in the responders of NACI‐treated HNSCC patients, while mIHC analysis confirmed the correlation between intratumoral CD103+CD8+ TILs density and NACI efficacy in HNSCC patients. Further receiver operating characteristic curve analysis defined this TIL subset as a potent marker to predict patient response to NACI. Functional assays showed that CD103+CD8+ TILs were tumor‐reactive T cells, while programmed cell death protein‐1 (PD‐1) blockade enhanced CD103+CD8+ TILs cytotoxicity against tumor growth in vivo. Mechanistically, targeting the triggering receptor expressed on myeloid cells 2‐positive (TREM2+) macrophages might enhance the population of CD103+CD8+ TILs and facilitate antitumor immunity during NACI treatment. Conclusions Our study highlights the impact of intratumoral CD103+CD8+ TILs density on NACI efficacy in different cancers, while the efforts to elevate its population warrant further clinical investigation.

As a transcription factor, Nuclear Receptor Subfamily 4 Group A Member 1 (NR4A1) binds to downstream target genes to participate in cell proliferation and cell differentiation. We found that the NR4A1 reached the highest expression at 60 h after the differentiation of goat intramuscular preadipocytes. Overexpression of goat NR4A1 increased the number of intracellular lipid droplets and up-regulated the expression of adipocyte-differentiation-related marker genes including AP2, SREBP1, ACC, GPAM, and DGAT2, while the relative expression levels of Pref-1 and HSL were significantly decreased. On the contrary, after NR4A1 was knocked down by siRNA, the number of intracellular lipid droplets and the relative expression levels of LPL, CEBPα, CEBPβ, ACC, and DGAT2 were significantly decreased, and the relative expression levels of Pref-1 and HSL were significantly up-regulated. These results suggest that NR4A1 promotes the differentiation of goat intramuscular preadipocytes. Transcriptome sequencing was carried out after overexpression of goat NR4A1, and the KEGG enrichment analysis result showed that the most differentially expressed genes were related to adipocyte differentiation and were enriched in the PI3K-Akt signaling pathway. LY249002, an inhibitor of the PI3K-Akt signaling pathway, was introduced and decreased the number of intracellular lipid droplets, and the relative expression levels of C/EBPα, SREBP1, AP2, C/EBPβ, GPAM, ACC, DGAT1, DGAT2, and ATGL were decreased accordingly. The above results indicate that overexpression of goat NR4A1 may promote the differentiation of intramuscular preadipocytes through the PI3K-Akt signaling pathway.

The melanoma-associated antigen (MAGE) family found in eukaryotes plays a crucial role in cell proliferation and differentiation, spermatogenesis, neural development, etc. This study explored the validation and evolution of MAGE genes in eukaryotic genomes and their distribution and expression patterns in pigs. In total, 249 MAGE genes were found on 13 eukaryotic species. In total, 33, 25, and 18 genes were located on human, mouse, and pig genomes, respectively. We found eight, four, and three tandemly duplicated gene clusters on the human, mouse, and pig genomes, respectively. The majority of MAGE genes in mammals are located on the X chromosome. According to the phylogenetic analysis, the MAGE family genes were classified into 11 subfamilies. The NDN gene in zebrafish (DreNDN) was the root of this evolutionary tree. In total, 10 and 11 MAGE genes on human and mouse genomes, respectively, exhibited a collinearity relationship with the MAGE genes on pig genomes. Taking the MAGE family genes in pigs, the MAGE subfamilies had similar gene structures, protein motifs, and biochemical attributes. Using the RNA-seq data of Duroc pigs and Rongchang pigs, we detected that the expression of type I MAGE genes was higher in reproductive tissues, but type II MAGE genes were predominantly expressed in the brain tissue. These findings are a valuable resource for gaining insight into the evolution and expression of the MAGE family genes.

Chromobacterium violaceum (C. violaceum) is a gram-negative bacillus that is widespread in tropical and subtropical areas. Although C. violaceum rarely infects humans, it can cause critical illness with a mortality rate above 50%. Here, we report the successful treatment of a 15-year-old male who presented with bloodstream infection of C. violaceum along with sepsis, specific skin lesions, and liver abscesses. Cardiogenic shock induced by sepsis was reversed by venoarterial extracorporeal membrane oxygenation (VA ECMO). Moreover, C. violaceum-related purpura fulminans, which is reported herein for the first time, was ameliorated after treatment. This case report demonstrates the virulence of C. violaceum with the aim of raising clinical awareness of this disease.

Summary: Distant metastasis is the main cause of death in patients with colorectal cancer (CRC). A better understanding of the mechanisms of metastasis can greatly improve the outcome of patients with CRC. Accumulating evidence suggests that circRNA plays pivotal roles in cancer progression and metastasis, especially acting as a miRNA sponge to regulate the expression of the target gene. A public database bioinformatics analysis found that miR-1825 was highly expressed in CRC tissues. In this study, miR-1825 was highly expressed in CRC tissues, which was positively correlated with lymph node metastasis and distant metastasis. In vitro and in vivo experiments confirmed that miR-1825 was positively correlated with the proliferation and migration of CRC cells. This event can be inhibited by circTBC1D22A. CircTBC1D22A can directly interact with miR-1825 and subsequently act as a miRNA sponge to regulate the expression of the target gene ATG14, which collectively advances the autophagy-mediated progression and metastasis of CRC.

Abstract Background The intra‐ and inter‐tumoral heterogeneity of gliomas and the complex tumor microenvironment make accurate treatment of gliomas challenging. At present, research on gliomas mainly relies on cell lines, stem cell tumor spheres, and xenotransplantation models. The similarity between traditional tumor models and patients with glioma is very low. Aims In this study, we aimed to address the limitations of traditional tumor models by generating patient‐derived glioma organoids using two methods that summarized the cell diversity, histological features, gene expression, and mutant profiles of their respective parent tumors and assess the feasibility of organoids for personalized treatment. Materials and Methods We compared the organoids generated using two methods through growth analysis, immunohistological analysis, genetic testing, and the establishment of xenograft models. Results Both types of organoids exhibited rapid infiltration when transplanted into the brains of adult immunodeficient mice. However, organoids formed using the microtumor method demonstrated more similar cellular characteristics and tissue structures to the parent tumors. Furthermore, the microtumor method allowed for faster culture times and more convenient operational procedures compared to the Matrigel method. Discussion Patient‐derived glioma organoids, especially those generated through the microtumor method, present a promising avenue for personalized treatment strategies. Their capacity to faithfully mimic the cellular and molecular characteristics of gliomas provides a valuable platform for elucidating tumor biology and evaluating therapeutic modalities. Conclusion The success rates of the Matrigel and microtumor methods were 45.5% and 60.5%, respectively. The microtumor method had a higher success rate, shorter establishment time, more convenient passage and cryopreservation methods, better simulation of the cellular and histological characteristics of the parent tumor, and a high genetic guarantee.

Abstract Objective Buccal mucosa cancer (BMC) is one of the most common oral cancers and has poor prognosis. The study aimed to develop and validate nomograms for predicting the 1‐, 3‐, and 5‐year overall survival (OS) and cancer‐specific survival (CSS) of BMC patients. Methods We collected and reviewed information on BMC patients diagnosed between 2004 and 2019 from the Surveillance Epidemiology and End Results database. Two nomograms were developed and validated to predict the OS and CSS based on predictors identified by univariate and multivariate Cox regression. An extra external validation was further performed using data from Sun Yat‐sen Memorial Hospital (SYSMH). Results A total of 3154 BMC patients included in this study were randomly assigned to training and validation groups in a 2:1 ratio. Independent prognostic predictors were identified, confirmed, and fitted into nomograms for OS and CSS, respectively. The C‐indices are 0.767 (Training group OS), 0.801 (Training group CSS), 0.763 (Validation group OS), and 0.781 (Validation group OS), respectively. Moreover, the nomograms exhibited remarkable precision in forecasting and significant clinical significance, as evidenced by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCA). The final validation using our data from SYSMH also showed high accuracy and substantial clinical benefits within the nomograms. The C‐indices are 0.849 (SYSMH group OS) and 0.916 (SYSMH group CSS). These indexes are better than tumor, node, and metastasis stage based on prediction results. Conclusions The nomograms developed with great performance predicted 1‐, 3‐, and 5‐year OS and CSS of BMC patients. Use of the nomograms in clinical practices shall bring significant benefits to BMC patients.

Elafin, which is derived from trappin-2 or pre-elafin by proteolysis, is an endogenous serine protease inhibitor with a low molecular weight. Its inhibitory activity is dependent on anchoring to the extracellular matrix by forming covalent bonds with its distinctive N-terminal domain via tissue transglutaminases. In addition to inhibiting proteases, it also exhibits anti-inflammatory, antibiotic, antifungal, antiviral and immunomodulatory functions. Elafin plays an important role in inflammatory disease and is a promising candidate for the anti-inflammatory treatment of respiratory diseases. This review will discuss the therapeutic potential of elafin in airway inflammation and provide evidence and suggestions for the future treatment of airway inflammatory diseases. In addition, the therapeutic potential of elafin in lung cancer is also discussed.

ObjectiveHuman identical sequences of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) promoted the coronavirus disease 2019 (COVID-19) progression by upregulating hyaluronic acid (HA) via NamiRNA-enhancer network, based on previous experimental research. This study aimed to investigate the predictive value of HA for the severity of SARS-CoV-2 infection in the post-COVID-19 era.MethodsA total of 217 consecutive patients with COVID-19 were enrolled at Beijing Ditan Hospital between July 2023 and October 2023. HA levels were analyzed using biochemical detector. Logistic regression analysis was used to screen independent factors for severe COVID-19. The predictive performance of HA for severe infection was assessed by ROC curve. Furthermore, the relationship between HA levels and COVID-19 severity was investigated using multivariate logistic regression models after adjustment for potential confounders.ResultsAccording to the cut-off value of HA, COVID-19 patients were divided into HA < 90 ng/mL group (80 cases) and HA ≥ 90 ng/mL group (137 cases). High HA levels were positively associated with the severe SARS-CoV-2 infection, including elevated inflammatory indicators, severe lung involvement, prolonged clinical course, and higher incidence of respiratory failure and death (P < 0.05). Logistic regression analysis suggested that HA was an independent predictor of severe COVID-19 (OR = 4.540, 95% CI = 2.105-9.790, P < 0.001). ROC curve analysis showed that the AUC of HA for severe infection was 0.724. HA levels were significantly higher in COVID-19 cases compared to the healthy population (123.9 (82.6, 174.1) vs. 50.5 (37.8, 66.8), P < 0.001), but similar to those with non-SARS-CoV-2 lung infection (121.6 (78.5, 175.6) vs. 106.0 (66.5, 149.7), P = 0.244). We also found that the first COVID-19 infections had higher HA levels (118.8 (79.5, 174.3) vs. 85.0 (61.1, 128.8), P < 0.001) and a higher proportion of severe infection (37.1% vs. 21.3%, P = 0.043) than re-infections. However, HA expression failed to fully return to normal levels with infection recovery (204.7 (152.9, 242.2) vs. 97.0 (69.3, 137.3), P < 0.001).ConclusionHA was associated with severe SARS-CoV-2 infection and could be used as a novel serum biomarker to predict the risk of COVID-19 progression in the post-COVID-19 era.

Summary: For almost two decades, clinicians have overlooked the diagnostic potential of CD34neg hematopoietic stem cells because of their limited homing capacity relative to CD34posHSCs when injected intravenously. This has contributed to the lack of appeal of using umbilical cord blood in HSC transplantation because its stem cell count is lower than bone marrow. The present study reveals that the homing and engraftment of CD34negHSCs can be improved by adding the Sialyl Lewis X molecule via α1,3-fucosylation. This unlocks the potential for using this more primitive stem cell to treat blood disorders because our findings show CD34negHSCs have the capacity to regenerate cells in the bone marrow of mice for several months. Furthermore, our RNA sequencing analysis revealed that CD34negHSCs have unique adhesion pathways, downregulated in CD34posHSCs, that facilitate interaction with the bone marrow niche. Our findings suggest that CD34neg cells will best thrive when the HSC resides in its microenvironment.