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Abstract We investigate the precessing motion around the the regular black hole with an asymptotically Minkowski core which has a suppression parameter $$\ell $$ ℓ . We obtain the third-order post-Newtonian quasi-Keplerian motion of a test particle in this spacetime and find its relativistic periastron advance. Then, we test this model with the precessing motion of the star S2 and of OJ 287 and determine the upper limits of the dimensionless suppression parameter as $$\ell /m \sim 10^{-3}$$ ℓ / m ∼ 10 - 3 , where m is the mass of the black hole. Compared with the bound given by the shadow of Sgr A*, our bound on $$\ell /m$$ ℓ / m is reduced by 2 orders of magnitude, although our upper limit of $$\ell $$ ℓ still needs further improvement.

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 Osteosarcoma (OS) is one of the most common primary malignant tumors of bone in children, which develops from osteoblasts and typically occurs during the rapid growth phase of the bone. Recently, Super-Enhancers(SEs)have been reported to play a crucial role in osteosarcoma growth and metastasis. Therefore, there is an urgent need to identify specific targeted inhibitors of SEs to assist clinical therapy. This study aimed to elucidate the role of BRD4 inhibitor GNE-987 targeting SEs in OS and preliminarily explore its mechanism. Methods We evaluated changes in osteosarcoma cells following treatment with a BRD4 inhibitor GNE-987. We assessed the anti-tumor effect of GNE-987 in vitro and in vivo by Western blot, CCK8, flow cytometry detection, clone formation, xenograft tumor size measurements, and Ki67 immunohistochemical staining, and combined ChIP-seq with RNA-seq techniques to find its anti-tumor mechanism. Results In this study, we found that extremely low concentrations of GNE-987(2–10 nM) significantly reduced the proliferation and survival of OS cells by degrading BRD4. In addition, we found that GNE-987 markedly induced cell cycle arrest and apoptosis in OS cells. Further study indicated that VHL was critical for GNE-987 to exert its antitumor effect in OS cells. Consistent with in vitro results, GNE-987 administration significantly reduced tumor size in xenograft models with minimal toxicity, and partially degraded the BRD4 protein. KRT80 was identified through analysis of the RNA-seq and ChIP-seq data. U2OS HiC analysis suggested a higher frequency of chromatin interactions near the KRT80 binding site. The enrichment of H3K27ac modification at KRT80 was significantly reduced after GNE-987 treatment. KRT80 was identified as playing an important role in OS occurrence and development. Conclusions This research revealed that GNE-987 selectively degraded BRD4 and disrupted the transcriptional regulation of oncogenes in OS. GNE-987 has the potential to affect KRT80 against OS.

Abstract Three-dimensional (3D) imaging of individual atoms is a critical tool for discovering new physical phenomena and developing new technologies in microscopic systems. However, the current single-atom-resolved 3D imaging methods are limited to static circumstances or a shallow detection range. Here, we demonstrate a generic dynamic 3D imaging method to track the extensive motion of single ions by exploiting the engineered point-spread function (PSF). We show that the image of a single ion can be engineered into a helical PSF, thus enabling single-snapshot acquisition of the position information of the ion in the trap. A preliminary application of this technique is demonstrated by recording the 3D motion trajectory of a single trapped ion and reconstructing the 3D dynamical configuration transition between the zig and zag structures of a 5-ion crystal. This work opens the path for studies on single-atom-resolved dynamics in both trapped-ion and neutral-atom systems.

Abstract When traditional statistical quality control protocols, represented by the Westgard protocol were applied to infectious disease serology, the rejection limits were questioned because of the high rejection probability. We first define the probability of false rejection (Pfr) and error detection (Ped) for infectious disease serology. QC data in 6 months were collected and the Pfr of each rule in the Westgard protocol and Rilibak protocol was evaluated. Then, as improvements, we chose different rules for negative and positive QC data to constitute an asymmetric protocol, furthermore, while reagent lot changes, the mean value of QC protocol is reset with the first 15 QC results of new lot reagent. QC materials and Standard Reference Materials were tested synchronously in the next 6 months, to verify whether the Pfr and Ped of the asymmetric protocol could meet the requirement. Protocol 1 exhibited the higher level of rejection rate among the two protocols, especially after reagent lot changes; Pfr below the lower control limit (LCL) was 1.39–21.78 times higher than the upper control limit (UCL); false rejections were more likely to occur in negative QC data, with Pfr-total of 27–65%. The asymmetric protocol can significantly reduce the proportion of analytes with Pfr by over 20%. Systematic error due to reagent lot changes and random error due to routine QC data variation were considered potential factors for excessive Pfr. Asymmetric QC protocol that can reduce Pfr by different control limits for negative and positive QC data.

Abstract Considerable attention has been directed towards exploring the potential efficacy of miR-155 in the realm of cancer immunotherapy. Elevated levels of miR-155 in dendritic cells (DCs) have been shown to enhance their maturation, migration, cytokine secretion, and their ability to promote T cell activation. In addition, overexpression of mir155 in M2 macrophages boost the polarization towards the M1 phenotype. Conversely, miR-155 has the propensity to induce the accumulation of immunosuppressive cells like regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in the tumor tissue. To account for this discrepancy, it is imperative to get help from a drug that could deal with immunosuppressive effect. Curcumin (CUR) exhibits the capacity to prompt Tregs converse into T helper 1 cells, fostering the polarization of M2 tumor-associated macrophage towards the M1 phenotype, and impeding the recruitment and aggregation of MDSCs within the tumor microenvironment. Nonetheless, CUR is known to exert an immunosuppressive impact on DCs by hindering the expression of maturation markers, cytokines, and chemokines, thereby prevent DCs response to immunostimulatory agents. Hence, a reactive oxygen species/glutathione dual responsive drug conveyance platform (CUR/miR155@DssD-Hb NPs) was devised to co-deliver CUR and miR155, with the aim of exploring their synergistic potential in bolstering a sustained and robust anti-tumor immune response. In vitro and in vivo results have suggested that CUR/miR155@DssD-Hb NPs can effectively inhibit the viability of 4T1 and B16F10 tumor cells, trigger the release of damage associated molecular patterns, stimulate DCs maturation, subsequent activation of CD8+ T cells, diminish immunosuppressive cell populations (MDSCs, Tregs, M2 TAMs and exhausted T cells), promote the formation of long-term immunity and lessen the formation of metastatic nodules in the lungs. In summary, the co-delivery system integrating CUR and miR155 (CUR/miR155@DssD-Hb NPs) demonstrates promise as a promising strategy for the immunotherapy of melanoma and triple negative breast cancer. Graphical abstract

ObjectiveTo explore the status of knowledge graph-based research into breast cancer microenvironment and to predict future research hotspots. MethodsThe literature related to breast cancer microenvironment in recent 20 years was retrieved from CNKI and Web of Science Core Collection database and analyzed with CiteSpace and VOSviewer. ResultsA total of 825 Chinese articles and 16,221 English articles were retrieved. Visual analysis showed that research focus has gradually shifted from cellular research to molecular research and drug innovation. Cancer stem cells, PD-1, PD-L1, immune checkpoint inhibitors, and nanoparticles are the main subjects of interest in research on breast cancer microenvironment, and the United States has the largest number of studies on breast cancer microenvironment, followed by China and Italy. ConclusionCurrent research mainly focuses on tumor stemness, immunotherapy, and nanodelivery. Owing to deepening research in this field, the targeting of the breast cancer microenvironment for the prevention of tumor development and metastasis and improvement of tumor prognosis has emerged as a new research direction.

Introduction: The use of the dorsal hamate as a free osteochondral bone graft or vascularized bone flap has become the mainstay for large, comminuted middle phalanx volar lip fractures. To date, few studies have been conducted in the assessment of donor site morbidity for the hemi-hamate graft or flap, and none have discussed modes of repair or reconstruction of this donor site. Methods: A retrospective analysis of 14 hemi-hamate arthroplasty (HHA) procedures, including 6 vascularized and 8 non-vascularized grafts, from two surgeons was performed. Four hamate defect reconstruction techniques were utilized: no formal reconstruction, autologous bone grafting, gel foam, or synthetic bone substitute. The dorsal capsule was repaired with either extensor retinaculum grafting or by direct closure. Wrist range of motion, pain scores, and radiographic alignment were assessed. Results: At 6 months follow-up, all patients achieved full, pain-free wrist motion compared to the uninjured side, with visual analog scale pain scores of 0. Serial radiographs showed maintained carpal alignment without instability or subluxation. No differences based on the hamate defect reconstruction method or capsular repair technique was demonstrated. Conclusion: Safe return to pain free, unrestricted wrist function is achievable after HHA, regardless of hamate donor site management. Adequate dorsal capsular repair appears critical to prevent instability. Further study is needed to compare techniques, but choice may be guided by surgeon preference in the absence of clear evidence.

Introduction. Low-cost, accurate high-risk HPV tests are needed for cervical cancer screening in limited-resource settings. Objective. To compare the performance of the low-cost Hybribio-H13 test with the Hybrid Capture® 2 to detect cervical intraepithelial neoplasia grade 2 or 3 (CIN2 and CIN3). Materials and methods. Archived baseline samples tested by the Hybrid Capture® 2 from women of the ASCUS-COL trial, aged 20 to 69 years, with biopsy-colposcopy directed diagnosis of CIN2+ (n = 143), CIN3+ (n = 51), and < CIN2 (n = 632) were blindly tested by the Hybribio-H13 test. Results. The relative sensitivity of the Hybribio-H13 test versus the Hybrid Capture® 2 for detecting CIN2+ was 0.89 (90% CI = 0,80-0,98; NIT = 0,66), and for CIN3+ was 0,92 (90% CI = 0,85-0,98; NIT = 0,35). Relative specificity was 1.19 (90% CI = 1.05-1.33; NIT

Abstract Nao-an Dropping Pill (NADP) is a Chinese patent medicine which commonly used in clinic for ischemic stroke (IS). However, the material basis and mechanism of its prevention or treatment of IS are unclear, then we carried out this study. 52 incoming blood components were resolved by UHPLC-MS/MS from rat serum, including 45 prototype components. The potential active prototype components hydroxysafflor yellow A, ginsenoside F1, quercetin, ferulic acid and caffeic acid screened by network pharmacology showed strongly binding ability with PIK3CA, AKT1, NOS3, NFE2L2 and HMOX1 by molecular docking. In vitro oxygen–glucose deprivation/reperfusion (OGD/R) experimental results showed that NADP protected HA1800 cells from OGD/R-induced apoptosis by affecting the release of LDH, production of NO, and content of SOD and MDA. Meanwhile, NADP could improve behavioral of middle cerebral artery occlusion/reperfusion (MCAO/R) rats, reduce ischemic area of cerebral cortex, decrease brain water and glutamate (Glu) content, and improve oxidative stress response. Immunohistochemical results showed that NADP significantly regulated the expression of PI3K, Akt, p-Akt, eNOS, p-eNOS, Nrf2 and HO-1 in cerebral ischemic tissues. The results suggested that NADP protects brain tissues and ameliorates oxidative stress damage to brain tissues from IS by regulating PI3K/Akt/eNOS and Nrf2/HO-1 signaling pathways.

Abstract Background Elizabethkingia is emerging as an opportunistic pathogen in humans. The aim of this study was to investigate the clinical epidemiology, antimicrobial susceptibility, virulence factors, and genome features of Elizabethkingia spp. Methods Clinical data from 71 patients who were diagnosed with Elizabethkingia-induced pneumonia and bacteremia between August 2019 and September 2021 were analyzed. Whole-genome sequencing was performed on seven isolates, and the results were compared with a dataset of 83 available Elizabethkingia genomes. Genomic features, Kyoto Encyclopedia of Genes and Genomes (KEGG) results and clusters of orthologous groups (COGs) were analyzed. Results The mean age of the patients was 56.9 ± 20.7 years, and the in-hospital mortality rate was 29.6% (21/71). Elizabethkingia strains were obtained mainly from intensive care units (36.6%, 26/71) and emergency departments (32.4%, 23/71). The majority of the strains were isolated from respiratory tract specimens (85.9%, 61/71). All patients had a history of broad-spectrum antimicrobial exposure. Hospitalization for invasive mechanical ventilation or catheter insertion was found to be a risk factor for infection. The isolates displayed a high rate of resistance to cephalosporins and carbapenems, but all were susceptible to minocycline and colistin. Genomic analysis identified five β-lactamase genes (bla GOB, bla BlaB, bla CME, bla OXA, and bla TEM) responsible for β-lactam resistance and virulence genes involved in stress adaptation (ureB/G, katA/B, and clpP), adherence (groEL, tufA, and htpB) and immune modulation (gmd, tviB, cps4J, wbtIL, cap8E/D/G, and rfbC). Functional analysis of the COGs revealed that “metabolism” constituted the largest category within the core genome, while “information storage and processing” was predominant in both the accessory and unique genomes. The unique genes in our 7 strains were mostly enriched in KEGG pathways related to microRNAs in cancer, drug resistance (β-lactam and vancomycin), ABC transporters, biological metabolism and biosynthesis, and nucleotide excision repair mechanisms. Conclusion The Elizabethkingia genus exhibits multidrug resistance and carries carbapenemase genes. This study presents a comparative genomic analysis of Elizabethkingia, providing knowledge that facilitates a better understanding of this microorganism.

A 60-day feeding trial was conducted to investigate the effects of dietary marine red yeast supplementation on growth performance, body composition, antioxidant, immunity, lipid metabolism, and mTOR signaling pathway in juvenile GIFT tilapia (Initial weight 21.12 ± 0.86 g). Five isonitrogenous and isolipidic experimental diets were formulated with graded levels of marine red yeast: 0 % (control group), 0.25 %, 0.50 %, 0.75 %, and 1.00 %. The results showed that different marine red yeast levels significantly increased (p < 0.05) the final weight, weight gain rate, specific growth rate, daily growth index, protein efficiency ratio, and condition factor, while significantly decreased (p < 0.05) the feed conversion ratio, viscera index, and hepatosomatic index. Different marine red yeast levels significantly increased (p < 0.05) the activities of foregut lipase, hindgut lipase, foregut α-amylase, midgut α-amylase, hindgut α-amylase, superoxide dismutase, catalase, glutathione peroxidase, and total antioxidant capacity, while the malondialdehyde content expressed an opposite trend. Different marine red yeast levels significantly increased (p < 0.05) the activities (contents) of lysozyme, alkaline phosphatase, immunoglobulin M, and complement protein 3 in serum. Different marine red yeast levels significantly increased (p < 0.05) the relative expression of phosphoryl inositol-3-kinase, protein kinase B, mammalian target of rapamycin, ribosome S6 protein kinase 1, cholesterol response element binding protein 1, peroxisome proliferator-activated receptor γ, leptin, acetyl-CoA carboxylase α, fatty acid synthase, and glucose-6-phosphate dehydrogenase in liver, while the relative expression of PPARα, carnitine palmitoyl transferase 1, lipoprotein lipase, and hormone sensitive lipase expressed an opposite trend. In conclusion, dietary supplementation with marine red yeast significantly increased the growth performance, antioxidant capacity, initial immunity, lipid synthesis, and mTOR signaling pathway in juvenile GIFT tilapia. Based on the second-order polynomial regression analysis, the optimal dietary marine red yeast level was between 0.53 % and 0.60 %.

Summary: Klebsiella aerogenes is an understudied and clinically important pathogen. We therefore investigate its population structure by genome analysis aligned with metadata. We sequence 130 non-duplicated K. aerogenes clinical isolates and identify two inter-patient transmission events. We then retrieve all publicly available K. aerogenes genomes (n = 1,026, accessed by January 1, 2023) and analyze them with our 130 genomes. We develop a core-genome multi-locus sequence-typing scheme. We find that K. aerogenes is a species complex comprising four phylogroups undergoing evolutionary divergence, likely forming three species. We delineate remarkable clonal diversity and identify three worldwide-distributed carbapenemase-encoding clonal clusters, representing high-risk lineages. We uncover that K. aerogenes has an open genome equipped by a large arsenal of antimicrobial resistance genes. We identify two genetic regions specific for K. aerogenes, encoding a type VI secretion system and flagella/chemotaxis for motility, respectively, both contributing to the virulence. These results provide much-needed insights into the population structure and pan-genomes of K. aerogenes.

Cadmium could induce various degrees of harm to aquatic organisms. A 30-day feeding trial was conducted to investigate the effects of cadmium on growth, muscle composition, digestive enzyme activity, gene expression of antioxidants and lipid metabolism in juvenile genetic improvement of farmed tilapia (GIFT, Oreochromis niloticus, Initial weight: 21.36 ± 0.24 g). Four cadmium concentrations of aquaculture water were designed: 0, 0.2, 0.4, and 0.6 mg/L Cd2+. The main results are as follows: Compared with the control group (0 mg/L Cd2+), the weight gain rate (WGR), specific growth rate (SGR), daily growth index (DGI), and spleen index (SI) of juvenile GIFT under cadmium stress were significantly decreased (p< 0.05). The contents of crude protein and crude lipid in muscle were significantly decreased (p< 0.05), and the ash was significantly increased (p< 0.05). The activities of trypsin, lipase, and α-amylase in the intestinal were significantly decreased (p< 0.05). The relative expression levels of carnitine palmityl transferase 1 (cpt-1), peroxisome proliferator-activated receptor α (pparα), pparγ, hormone-sensitive lipase (hsl), lipoprotein lipase (lpl), malate dehydrogenase (mdh), leptin (lep), fatty acid synthetase (fas), cholesterol response element binding protein 1 (srebp1), squalene cyclooxygenase (sqle), and stearoyl-CoA desaturase (scd) genes in liver were significantly decreased (p< 0.05). The relative expression levels of catalase (cat), superoxide dismutase (sod), glutathione S-transferase (gst), and glutathione peroxidase (gsh-px) genes in the liver were significantly decreased (p< 0.05). In conclusion, exposure to cadmium stress could impact growth, muscle composition, digestive enzyme activity, gene expression of antioxidant and lipid metabolism in juvenile GIFT.

Background and aimThe teaching profession plays an important role in shaping individuals’ lives, with teachers performing complex emotional labour. The management of emotions is an integral part of teachers’ professional work, and it is essential to clarify their emotional experiences and the generating of their emotions within a specific cultural context.MethodsBased on a phenomenological approach and the use of anecdotal texts, this study examined six common emotional states among teachers, including happiness, guilt, worry, fear, annoyance, and anger, along with the emotional experiences of two specialised categories of teachers, class supervisors, and pre-service teachers. The factors influencing teachers’ emotions and their generative mechanisms were analysed.Results and discussionThis investigation found that key influences on teachers’ emotions stem from factors within the teachers’ themselves, the contextual nature of their work, and sociocultural dynamics. Drawing on the analytical frameworks of emotional geography theory, ecological theory of human development, and the ecosystem model of teachers’ emotional interactions, the study constructs a model highlighting the generative mechanisms of teachers’ emotions, and in which three systems are reflected.ConclusionTeachers’ personal attributes are in the direct area of the model and directly govern the formation of their emotions, while their work context consists of a transitional area in emotion formation and the sociocultural system acts as the latent band influencing emotion development. The mechanism model helps us to understand and recognise teachers’ emotions and to explore their pedagogical implications.

Abstract Deep shale gas development has great potential, but the frequent occurrence of shale gas well casing change problems triggered by geological factors seriously restricts deep shale gas development. In order to investigate the influence of geological factors on the casing stress of the cemented casing in the sleeve, a model of formation-cement sheath-double casing assemblage was established, and the influence of three-way geostress and fault slip on the casing stress of the casing-in-casing cementing was investigated by using finite element analysis. The results show the following: the smaller the difference between the vertical geostress and the maximum horizontal geostress is, the lower the equivalent force on the casing is, and when the difference gradually decreases from 20 to 7 MPa, the maximum equivalent force of the inner casing under fracturing condition decreases by 9.4%; the increase of the minimum horizontal geostress leads to the increase of the equivalent force of the inner and outer casing. When the minimum horizontal stress gradually increases from 80 to 90 MPa, the maximum equivalent force of the inner casing under fracturing condition increases by 5.9%. The larger the fault slip and the fault angle, the larger the equivalent force generated on the casing. The shear resistance of the double-layer casing is significantly greater than that of the single-layer casing, with an average increase in fault slip distance that can be withstood of about 45.25% and 40.2% in the no internal pressure and fracturing conditions. The larger the casing steel grade and the thicker the wall thickness, the higher the shear resistance. It is recommended to reduce placing of wells in areas where the difference between the vertical and maximum horizontal ground stresses is large, and at locations where the fault slip angle is large, and to use both higher steel grades and larger wall thicknesses of casing. This research result demonstrates the feasibility of “milling + casing-in-casing” technology in severe casing change wells and also provides useful guidance for the application of this technology in the field.

Abstract Group 1 elements exhibit the lowest electronegativity values in the Periodic Table. The chemical reduction of Group 1 metal cations M+ to M(0) is extremely challenging. Common tetraaryl borates demonstrate limited redox properties and are prone to decomposition upon oxidation. In this study, by employing simple yet versatile bipyridines as ligands, we synthesized a series of redox-active borate anions characterized by NMR and X-ray single-crystal diffraction. Notably, the borate anion can realize the reduction of Li+, generating elemental lithium metal and boron radical, thereby demonstrating its potent reducing ability. Furthermore, it can serve as a powerful two-electron-reducing reagent and be readily applied in various reductive homo-coupling reactions and Birch reduction of acridine. Additionally, this borate anion demonstrates its catalytic ability in the selective two-electron reduction of CO2 into CO.

Abstract Background To investigate the role of antimicrobial prophylaxis in laparoscopic nephrectomy for renal cell carcinoma. Methods We retrospectively enrolled 1000 patients who underwent laparoscopic nephrectomy from August 2019 to November 2021 in the Peking Union Medical College Hospital. Patients were divided into group without antimicrobial prophylaxis (n = 444) and group with antimicrobial prophylaxis (n = 556). Outcomes including 30-day postoperative infection rate, the increase rate of pre- and post-operative white blood cell counts and hospital stay were analyzed. Results The overall infection rate was 5.0% (28/556) in the group with antimicrobial prophylaxis, which was similar to 4.1% (18/444) in the group without antimicrobial prophylaxis (P = 0.461). The increase rate of pre- and post-operative white blood cell counts was significantly lower (85.5% versus 97.0%) in the group with antimicrobial prophylaxis (P = 0.004). The postoperative hospital stay was 5 (4, 6) days in both groups (P = 0.483). Logistic regression analyses identified the use of antimicrobial prophylaxis had no influence on the occurrence of infection events (odds ratio = 0.797; 95% confidence interval, 0.435–1.460; P = 0.462). Hemoglobin (odds ratio = 0.430; 95% confidence interval, 0.257–0.719; P = 0.001) and partial nephrectomy (odds ratio = 2.292; 95% confidence interval, 1.724–3.046; P

Millimeter waves are electromagnetic waves with wavelengths of 1–10 mm, which have characteristics of high frequency and short wavelength. They have gradually and widely been used in engineering and medical fields. We have identified studies related to millimeter waves in the biomedical field and summarized the biological effects of millimeter waves and their current status in medical applications. Finally, the shortcomings of existing studies and future developments were analyzed and discussed, with the aim of providing a reference for further research and development of millimeter waves in the medical field.

Abstract The Fscn2 (Fascin2) gene encodes an actin cross-linking protein that is involved in the formation of hair cell stereocilia and retina structure. Mutations in Fscn2 gene have been linked to hearing impairment and retinal degeneration in humans and mice. To understand the function of the Fscn2 gene, we generated the Fscn2 knockout mice, which showed progressive loss of hearing and hair cells. Our goal of the present study was to investigate the mechanism underlying cochlear cell death in the Fscn2 knockout mice. Microarray analysis revealed upregulation of expression of PARVB, a local adhesion protein, in the inner ears of Fscn2 knockout mice at 8 weeks of age. Further studies showed increased levels of PARVB together with cleaved-Caspase9 and decreased levels of ILK, p-ILK, p-AKT, and Bcl-2 in the inner ears of Fscn2 knockout mice of the same age. Knockdown of Fscn2 in HEI-OCI cells led to decreased cell proliferation ability and migration rate, along with increased levels of PARVB and decreased levels of ILK, p-ILK, p-AKT, Bcl-2 and activated Rac1 and Cdc42. Overexpression of Fscn2 or inhibition of Parvb expression in HEI-OC1 cells promoted cell proliferation and migration, with increased levels of ILK, p-ILK, p-AKT, and Bcl-2. Finally, FSCN2 binds with PPAR-γ to reduce its nuclear translocation in HEI-OC1 cells, and inhibition of PPAR-γ by GW9662 decreased the level of PARVB and increased the levels of p-AKT, p-ILK, and Bcl-2. Our results suggest that FSCN2 negatively regulates PARVB expression by inhibiting the entry of PPAR-γ into the cell nucleus, resulting in inhibition of ILK-AKT related pathways and of cochlear cell survival in Fscn2 knockout mice. Our findings provide new insights and ideas for the prevention and treatment of genetic hearing loss.

Abstract Airway epithelial transcriptome analysis of asthma patients with different severity was used to disentangle the immune infiltration mechanisms affecting asthma exacerbation, which may be advantageous to asthma treatment. Here we introduce various bioinformatics methods and develop two models: an OVA/CFA-induced neutrophil asthma mouse model and an LPS-induced human bronchial epithelial cell damage model. Our objective is to investigate the molecular mechanisms, potential targets, and therapeutic strategies associated with asthma severity. Multiple bioinformatics methods identify meaningful differences in the degree of neutrophil infiltration in asthma patients with different severity. Then, PTPRC, TLR2, MMP9, FCGR3B, TYROBP, CXCR1, S100A12, FPR1, CCR1 and CXCR2 are identified as the hub genes. Furthermore, the mRNA expression of 10 hub genes is determined in vivo and in vitro models. Reperixin is identified as a pivotal drug targeting CXCR1, CXCR2 and MMP9. We further test the potential efficiency of Reperixin in 16HBE cells, and conclude that Reperixin can attenuate LPS-induced cellular damage and inhibit the expression of them. In this study, we successfully identify and validate several neutrophilic signatures and targets associated with asthma severity. Notably, Reperixin displays the ability to target CXCR1, CXCR2, and MMP9, suggesting its potential therapeutic value for managing deteriorating asthma.

Physical separation of acetylene (C2H2) from carbon dioxide (CO2) or ethylene (C2H4) on metal–organic frameworks (MOFs) is crucial for achieving high-purity feed gases with minimal energy penalty. However, such processes are exceptionally challenging due to their close physical properties and are also critically restricted by the high cost of large-scale MOF synthesis. Here, we demonstrate the readily scalable synthesis of a highly water-resistant chiral Cu-MOF (TAMOF-1) based on an inexpensive proteogenic amino acid derivative bearing rich N/O sites. Notably, the unique coordination in this ultramicroporous MOF has resulted in the generation of rare global negative electrostatic potentials, which greatly facilitate the electrostatic interactions with C2H2 molecules, thus leading to their efficient separation from C2H2/CO2 and C2H2/C2H4 mixtures under ambient conditions. The separation efficiency and mechanism are unequivocally validated by breakthrough experiments and computational simulations. This work not only highlights the pivotal role of creating a negative electro-environment in confined spaces for boosting C2H2 capture and separation but also opens up new ways of employing cheap amino acid derivatives bearing rich electro-negative N and O sites as organic linkers to constructing high-performing MOF materials for gas separation purposes.

Abstract Breast cancer is the second leading cause of death in women worldwide, with triple-negative breast cancer (TNBC) having the worst prognosis. Although there are numerous studies on TNBC, there is no effective treatment for it, and it is still a major problem today. Studies on PIWI-interacting RNAs (piRNAs) are increasing and investigating the mechanism of piRNAs in the proliferation and metastasis of TNBC may lead to new potential treatment targets. Here, we identified a novel piRNA, piR-YBX1, which was downregulated in TNBC compared to matched normal breast tissue. Overexpression of piR-YBX1 significantly inhibited the proliferation, migration, invasion ability of TNBC cells both in vivo and in vitro. Mechanistically, piR-YBX1 could bind directly to mRNA of Y-box binding protein 1 (YBX1) and overexpression of piR-YBX1 downregulated YBX1 in both mRNA and protein levels, while the function of piR-YBX1 could be partly rescued by overexpression of YBX1. In addition, YBX1 could bind to RAF1 which is the key molecule in the MAPK signaling pathway, and overexpression of piR-YBX1 inhibited the p-MEK and p-ERK1/2, which can be reverted by YBX1. In conclusion, our findings discovered that the piR-YBX1/YBX1/MAPK axis suppresses the proliferation and metastasis of TNBC and therefore piR-YBX1 has the potential to be an effective therapeutic agent for breast cancer.

Under non-Gauss noise condition, the performance of traditional state estimation methods based on Gauss measurement noise will be greatly reduced. In order to solve this problem, a robust state estimation method based on Mahalanobis distance under non-Gauss noise is proposed in this paper. First of all, based on the Mahalanobis distance, the calculation method of optimal buffer length for PMU measurements is used, which can unify the SCADA measurements with PMU measurements in the same snapshot. Then, Based on the two-stage processing method, in the first stage, the SCADA measurements are used for filtering by using maximum likelihood estimator to obtain the estimated values, and then the estimated values in the first-stage are combined with PMU measurements as the second-stage measurements for filtering, and finally the final results are obtained. Based on the IEEE-39 buses system and IEEE-118 buses system, under Gaussian noise and non-Gaussian noise, the AEE results of proposed method are very small, and which are all within 10−3, numerical tests under different simulation conditions verified the robustness and effectiveness.

Abstract Background In recent years, breast cancer (BC) incidence and mortality have been the highest in females. Menopause-like syndrome (MLS), arising from hypoestrogenism caused by endocrine therapy, significantly affects the quality of life for females. Traditional Chinese Medicine (TCM) has advantages in ameliorating MLS, but the efficacy of TCM in patients with BC has not been systematically evaluated. Methods A comprehensive search was performed on PubMed, Web of Science, Embase, Ovid, Cochrane Library, China National Knowledge Infrastructure, Wanfang database, Chinese Scientific Journals Database, and Clinical Trial Registry from inception to September 4, 2023. The Cochrane Risk of Bias assessment tool was used for the quality evaluation of the randomized controlled trials (RCTs). Review Manager 5.4 software was used for statistical analysis, and the Grading of Recommendations Assessment, Development, and Evaluation was used for quality evaluation of the synthesized evidence. Results This review included 42 studies involving 3112 female patients with BC. The results showed that the TCM group was better at decreasing the Kupperman Menopausal Index (KMI) scores (standardized MD, SMD = − 1.84, 95% confidence interval, CI [− 2.21–-1.46], Z = 9.63, P

This study aimed to investigate the effects of dietary Bacillus cereus supplementation on the growth performance, serum biochemistry, intestinal health, and Nrf2 and TLR/NF-κB signaling pathways of juvenile coho salmon (Oncorhynchus kisutch). Four different concentrations of B. cereus in the feed were prepared: 0 (control group), 2×107 CFU/g, 4×109 CFU/g, and 8×1011 CFU/g. Each group had three replicates, and each replicate was fed 20 juvenile coho salmon (initial body weight = 128.78 ± 5.75 g) for 10 weeks. Results showed that the addition of B. cereus to the weight gain rate, specific growth rate, feed conversion ratio, protein efficiency ratio, crude protein, and expression of nuclear factor erythroid 2-related factor 2, kelch-like ECH-associated protein 1B, glutathione peroxidase, glutathione S-transferase, glutathione-disulfide reductase, superoxide dismutase, catalase, toll like receptor 3 (TLR3), TLR7, heat shock protein family A member 8 (Hsp70), lysozyme, complement C3, nuclear factor NF-kappa-B, tumor necrosis factor, transforming growth factor beta, interferon gamma, interleukin-1 beta, interleukin-6, and interleukin-8 genes, as well as serum physiological and biochemical and liver antioxidant enzyme activity indicators, were significantly affected (P < 0.05). It could effectively improve the intestinal structure, intestinal flora, and function. However, the survival rate did not significantly differ among the groups (P > 0.05). In conclusion, the addition of B. cereus at a concentration of 4×109 CFU/g to diets can effectively promote the growth of juvenile coho salmon, enhance antioxidant and immune capabilities, and improve intestinal health.

Marine red yeast is a good feed additive for the aquaculture industry that can promote the growth of aquatic animals, and significantly improve their antioxidant capacity, survival rate, and nonspecific immune ability of the body. Our hypothesis is that dietary supplementation with marine red yeast could affect the serum biochemistry, muscle composition, muscle fatty acid composition, lipid metabolism enzyme activity, and expression of antioxidant and inflammatory genes in juvenile genetically improved farmed tilapia (GIFT, Oreochromis niloticus). Five diets with different levels of marine red yeast (0 %, 0.25 %, 0.50 %, 0.75 %, and 1.00 %) were used to feed juvenile GIFT (initial weight: 21.12 ± 0.86 g) for 60 days. The main results are as follows: Compared with the control group (0 % marine red yeast), the contents of total protein (TP), albumin (ALB), high-density lipoprotein (HDL), and free fatty acid (FFA) in the serum of juvenile GIFT tilapia significantly increased (P < 0.05), while the contents of glucose (GLU), triglyceride (TG), total cholesterol (T-CHO), low-density lipoprotein (LDL), alanine aminotransferase (ALT) significantly decreased (P < 0.05). The contents of crude protein, crude fat, and docosahexaenoic acid + eicosapentaenoic acid (DHA+EPA) in the muscle significantly increased (P < 0.05), while the contents of moisture and monounsaturated fatty acids (∑MUFAs) significantly decreased (P < 0.05). The activities of acetyl CoA carboxylase α (ACCα), glucose-6-phosphate dehydrogenase (G6PD), and stearoyl-CoA desaturase (SCD) in the liver significantly increased (P < 0.05). The expression levels of catalase (cat), alkaline phosphatase (alp), nuclear factor erythroid 2-related factor 2 (nrf2), lysozyme (lyz), glutathione S-transferase (gst), glutathione peroxidase (gsh-px), and superoxide dismutase (sod) genes in the liver significantly increased (P < 0.05). The expression levels of tumor necrosis factor α (tnf-α), interferon-γ (inf-γ), interleukin 6 (il-6), interleukin 8 (il-8), interleukin 1β (il-1β), and transforming growth factor-β (tgf-β1) genes in the liver, spleens, and head kidney significantly increased (P < 0.05), while the expression level of interleukin 10 (il-10) gene significantly decreased (P < 0.05). In conclusion, the addition of different levels of marine red yeast could significantly affect the serum biochemistry, muscle composition, muscle fatty acid composition, lipid metabolism enzyme activity, and expression of antioxidant and inflammatory genes in juvenile GIFT tilapia. Based on the results, the optimal dietary marine red yeast level was 0.50 %.

Abstract Plasmaspheric hiss, a whistler‐mode emission confined in the high‐density plasmasphere, is of great interest to the space community attributed to its important role in inner magnetospheric dynamics. Their frequency‐time structures provide crucial evidence for understanding the wave origin. In this work, based on ∼7‐year Van Allen Probes data, we statistically studied the frequency‐drifting plasmaspheric hiss characterized by an increasing lower cutoff frequency over a timescale exceeding 1 hr. Frequency‐drifting hiss waves predominantly occur at 3

PCDD/Fs are dioxins produced by waste incineration and pose risks to human health. We aimed to detail the health risks of airborne and soil PCDD/Fs near a municipal solid-waste incinerator (MSWI) for the surrounding population and develop a new model that improves upon existing methods. Thus, we conducted field sampling and then investigated a MSWI in the Pearl River Delta (2016–2018). Our results showed that the carcinogenic and non-carcinogenic risk values of PCDD/Fs exposed to residents in nearby areas were acceptable, with hazard index (HI) values lower than 1.0 and a total carcinogenic risk lower than 1.0E-6. Notably, the results raised concerns regarding higher non-carcinogenic risks in children than in adults. Comparative analysis of the frequency accumulation diagram, accumulated probability risk, and the absolute value of error (δ) between the 95% confidence interval (CI) and the 90% CI of the Monte Carlo stochastic simulation-triangular fuzzy number (MCSS-TFN) and the MCSS model, respectively, demonstrated that the MCSS-TFN exhibited less uncertainty than the MCSS model, regardless of the health risk value of PCDD/Fs in ambient air or in soil. This observation underscores the superiority of the MCSS-TFN model over other models in assessing the health risks associated with PCDD/Fs in situations with limited data. Our new method overcomes the limited dataset size and high uncertainty in assessing the health risks of dioxin substances, providing a more comprehensive understanding of their associated health risks than MCSS models.

Abstract Background Steroid-resistant nephrotic syndrome (SRNS) is characterized by unrelieved proteinuria after an initial 4–8 weeks of glucocorticoid therapy. Genes in podocytes play an important role in causing SRNS. Objective This study aimed to report a pathogenic mutation in SRNS patients and investigate its effects on podocytes, as well as the pathogenic mechanism. Methods We screened out a novel mutation by using whole-exon sequencing in the SRNS cohort and verified it via Sanger sequencing. Conservative analysis and bioinformatic analysis were used to predict the pathogenicity of the mutation. In vitro, stable podocyte cell lines were constructed to detect the effect of the mutation on the function of the podocyte. Moreover, an in vivo mouse model of podocyte ANLN gene knockout (ANLN podKO) was used to confirm clinical manifestations. Transcriptome analysis was performed to identify differential gene expression and related signaling pathways. Results ANLN E841K was screened from three unrelated families. ANLN E841K occurred in the functional domain and was predicted to be harmful. The pathological type of A-II-1 renal biopsy was minimal change disease, and the expression of ANLN was decreased. Cells in the mutation group showed disordered cytoskeleton, faster cell migration, decreased adhesion, increased endocytosis, slower proliferation, increased apoptosis, and weakened interaction with CD2 association protein. ANLN podKO mice exhibited more obvious proteinuria, more severe mesangial proliferation, glomerular atrophy, foot process fusion, and increased tissue apoptosis levels than ANLN flox/flox mice after tail vein injection of adriamycin. Upregulated differentially expressed genes in cells of the mutation group were mainly enriched in the PI3K-AKT pathway. Conclusion The novel mutation known as ANLN E841K affected the function of the ANLN protein by activating the PI3K/AKT/mTOR/apoptosis pathway, thus resulting in structural and functional changes in podocytes. Our study indicated that ANLN played a vital role in maintaining the normal function of podocytes. Video Abstract

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 Self-testing allows one to characterise quantum systems under minimal assumptions. However, existing schemes rely on quantum nonlocality and cannot be applied to systems that are not entangled. Here, we introduce a robust method that achieves self-testing of individual systems by taking advantage of contextuality. The scheme is based on the simplest contextuality witness for the simplest contextual quantum system—the Klyachko-Can-Binicioğlu-Shumovsky inequality for the qutrit. We establish a lower bound on the fidelity of the state and the measurements as a function of the value of the witness under a pragmatic assumption on the measurements. We apply the method in an experiment on a single trapped 40Ca+ using randomly chosen measurements and perfect detection efficiency. Using the observed statistics, we obtain an experimental demonstration of self-testing of a single quantum system.

Excessive ultraviolet (UV) exposure can lead to sunburn, characterized by skin barrier damage, inflammation, pain, and an increased risk of skin cancer. Recombinant collagens have gradually attracted attention due to their high purity, low immunogenicity, batch-to-batch consistency, and excellent solubility. Additionally, the type of dressing significantly affects wound repair. Gels are ideal for sunburn treatment because they maintain a moist environment, adhere firmly, and do not need to be removed. Herein, we have created bioactive triple-helical recombinant collagen (THRC) gels for improved healing of sunburned skin. The THRC gels remained stable after a three-month stability test, displaying a rheological behavior characteristic of non-Newtonian pseudoplastic fluids. In vivo skin irritation tests conducted on New Zealand rabbits demonstrated that THRC gels were safe for use. A sunburned mice model was established to study the biological effects of THRC gels. Non-invasive combo evaluations indicated that THRC gels exhibited an exceptional capability of recovering dermis density, erythema index (EI), hydration, and transepidermal water loss (TEWL) of sunburned skin to a healthy state. Histological observations revealed that THRC gels significantly enhanced the repair of damaged skin by accelerating the recovery process, promoting collagen deposition and regeneration. Molecular biological characterizations further demonstrated their remarkable antioxidant properties, including the inhibition of lipoperoxidation and the enhancement in superoxide dismutase (SOD) and glutathione (GSH) activities. These safe and bioactive recombinant collagen gels provide a novel approach for sunburn repair and show potential for long-term cosmetic benefits.

The objective of this study was to examine the effects of varying levels of dietary chitosan supplementation on mitigating cadmium stress and its influence on growth performance, serum biochemical indices, antioxidant capacity, immune response, inflammatory response, and the expression of related genes in juvenile Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus). Five groups of juvenile tilapias (initial body weight 21.21 ± 0.24 g) were fed five diets with different levels (0%, 0.5%, 1.0%, 1.5%, and 2.0%) of chitosan supplementation for 60 days under cadmium stress (0.2 mg/L Cd2+). The findings indicated that, compared with the 0% chitosan group, dietary chitosan could significantly increase (p < 0.05) the final weight (Wf), weight gain rate (WGR), specific growth rate (SGR), daily growth index (DGI), and condition factor (CF), while the feed conversion ratio (FCR) expressed the opposite trend in juvenile GIFT. Dietary chitosan could significantly increase (p < 0.05) the activities (contents) of cholinesterase (CHE), albumin (ALB), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), acid phosphatase (ACP), and lysozyme (LZM), while glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), and complement 3 (C3) in the serum of juvenile GIFT expressed the opposite trend. Dietary chitosan could significantly increase (p < 0.05) the activities of superoxide dismutase (SOD) and catalase (CAT) and significantly decrease (p < 0.05) the activities (contents) of glutathione S-transferase (GST), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) in the serum of juvenile GIFT. Dietary chitosan could significantly increase (p < 0.05) the activities (contents) of CAT, GST, GSH-Px, and total antioxidant capacity (T-AOC) and significantly decrease (p < 0.05) the contents of MDA in the liver of juvenile GIFT. Dietary chitosan could significantly increase (p < 0.05) the activities (contents) of SOD, GSH-Px, T-AOC, Na+-K+-ATPase, and Ca2+-ATPase and significantly decrease (p < 0.05) the activities (contents) of CAT, GST, and MDA in the gills of juvenile GIFT. Dietary chitosan could significantly up-regulate (p < 0.05) the gene expression of cat, sod, gst, and gsh-px in the liver of juvenile GIFT. Dietary chitosan could significantly up-regulate (p < 0.05) the gene expression of interferon-γ (inf-γ) in the gills and spleen and significantly down-regulate (p < 0.05) the gene expression of inf-γ in the liver and head kidney of juvenile GIFT. Dietary chitosan could significantly down-regulate (p < 0.05) the gene expression of interleukin-6 (il-6), il-8, and tumor necrosis factor-α (tnf-α) in the liver, gills, head kidney, and spleen of juvenile GIFT. Dietary chitosan could significantly up-regulate (p < 0.05) the gene expression of il-10 in the liver, gills, head kidney, and spleen of juvenile GIFT. Dietary chitosan could significantly up-regulate (p < 0.05) the gene expression of transforming growth factor-β (tgf-β) in the liver and significantly down-regulate (p < 0.05) the gene expression of tgf-β in the head kidney and spleen of juvenile GIFT. In conclusion, dietary chitosan could mitigate the impact of cadmium stress on growth performance, serum biochemical indices, antioxidant capacity, immune response, inflammatory response, and related gene expression in juvenile GIFT. According to the analysis of second-order polynomial regression, it was found that the optimal dietary chitosan levels in juvenile GIFT was approximately 1.42% to 1.45%, based on its impact on Wf, WGR, SGR, and DGI.

Power lines are commonly utilized for energy transmission, and they serve as a conduit for data exfiltration or infiltration in some specific scenarios. This paper explores the feasibility of establishing bidirectional communication between a modified plug and the equipment power line within an air-gapped network organization and with external entities. Bidirectional air-gap communication includes two scenarios, the data leak from air-gapped networks and the transmission of external data to air-gapped networks, namely, exfiltration and infiltration. In the exfiltration scenario, software in the air-gapped networks modulates and encodes data by manipulating the power consumption of the equipment during transmission, which is then sent outside through the power line. The device utilizes a smart plug power meter to record current fluctuations and subsequently decode any leaked data. In the infiltration scenario, a smart plug is used to control the power supply status of a device’s power cord, enabling data encoding and decoding by turning the power supply on and off. The software in the air-gapped equipment captures and decodes the power supply status to infiltrate. We discuss relevant literature and provide scientific background on smart plugs and power line communication. We simulate the communication scenario, propose a communication scheme, and present data modulation techniques as well as a communication transmission protocol for air-gap channels. Our evaluation of the PowerBridge air-gap channels demonstrates that data can leak from the air-gapped computer into the power line at an approximate rate of 30 bps, which can be captured by the smart plug. Additionally, it is possible for data to penetrate from the smart plug into air-gapped networks at a speed exceeding 1 bps.

The objective of this research was to create a prognostic model focused on genes related to ubiquitination (UbRGs) for evaluating their clinical significance in head and neck squamous cell carcinoma (HNSCC) patients. The transcriptome expression data of UbRGs were obtained from The Cancer Genome Atlas (TCGA) database, and weighted gene co-expression network analysis (WGCNA) was used to identify specific UbRGs within survival-related hub modules. A multi-gene signature was formulated using LASSO Cox regression analysis. Furthermore, various analyses, including time-related receiver operating characteristics (ROCs), Kaplan–Meier, Cox regression, nomogram prediction, gene set enrichment, co-expression, immune, tumor mutation burden (TMB), and drug sensitivity, were conducted. Ultimately, a prognostic signature consisting of 11 gene pairs for HNSCC was established. The Kaplan–Meier curves indicated significantly improved overall survival (OS) in the low-risk group compared to the high-risk group (p < 0.001), suggesting its potential as an independent and dependable prognostic factor. Additionally, a nomogram with AUC values of 0.744, 0.852, and 0.861 at 1-, 3-, and 5-year intervals was developed. Infiltration of M2 macrophages was higher in the high-risk group, and the TMB was notably elevated compared to the low-risk group. Several chemotherapy drugs targeting UbRGs were recommended for low-risk and high-risk patients, respectively. The prognostic signature derived from UbRGs can effectively predict prognosis and provide new personalized therapeutic targets for HNSCC.

We analyze a time-delayed SIQR model that considers transportation-related infection and entry–exit screening. This model aims to determine the measures for preventing and controlling major emergent infectious diseases and the associated costs. We calculate the basic reproduction number (R0) and prove that the disease-free equilibrium is locally and globally asymptotically stable. We collect COVID-19 infection data from two regions in the United States in 2020 for data fitting, obtain a set of optimal parameter values, and find that transportation-related infection rates increase the basic reproduction number, enhancing the impact on disease spread. Entry–exit screening effectively suppresses the spread of disease by reducing the basic reproduction number. Furthermore, we investigate the influence of the incubation period on disease and find that a shorter incubation period results in a shorter duration but a larger scale of infection and that the peaks are reduced. We conduct a sensitivity analysis of the R0 and propose three measures to prevent the spread of new infectious diseases based on the most sensitive parameters: wearing masks, implementing urban closures, and administering medication to sick but not yet hospitalized patients promptly. In the case of COVID-19, optimal control effectively controls the development and deterioration of the disease. Finally, several control measures are compared through cost-effectiveness analysis, and the results show that wearing masks is the most cost-effective measure.

Abstract Disruption of disulfide homeostasis during biological processes can have fatal consequences. Excess disulfides induce cell death in a novel manner, termed as “disulfidptosis.” However, the specific mechanism of disulfidptosis has not yet been elucidated. To determine the cancer types sensitive to disulfidptosis and outline the corresponding treatment strategies, we firstly investigated the crucial functions of disulfidptosis regulators pan‐cancer at multi‐omics levels. We found that different tumor types expressed dysregulated levels of disulfidptosis regulators, most of which had an impact on tumor prognosis. Moreover, we calculated the disulfidptosis activity score in tumors and validated it using multiple independent datasets. Additionally, we found that disulfidptosis activity was correlated with classic biological processes and pathways in various cancers. Disulfidptosis activity was also associated with tumor immune characteristics and could predict immunotherapy outcomes. Notably, the disulfidptosis regulator, glycogen synthase 1 (GYS1), was identified as a promising target for triple‐negative breast cancer and validated via in vitro and in vivo experiments. In conclusion, our study elucidated the complex molecular phenotypes and clinicopathological correlations of disulfidptosis regulators in tumors, laying a solid foundation for the development of disulfidptosis‐targeting strategies for cancer treatment.

Abstract Neuro‐COVID, a condition marked by persistent symptoms post‐COVID‐19 infection, notably affects various organs, with a particular focus on the central nervous system (CNS). Despite scant evidence of SARS‐CoV‐2 invasion in the CNS, the increasing incidence of Neuro‐COVID cases indicates the onset of acute neurological symptoms early in infection. The Omicron variant, distinguished by heightened neurotropism, penetrates the CNS via the olfactory bulb. This direct invasion induces inflammation and neuronal damage, emphasizing the need for vigilance regarding potential neurological complications. Our multicenter study represents a groundbreaking revelation, documenting the definite presence of SARS‐CoV‐2 in the cerebrospinal fluid (CSF) of a significant proportion of Neuro‐COVID patients. Furthermore, notable differences emerged between RNA‐CSF‐positive and negative patients, encompassing aspects such as blood–brain barrier integrity, extent of neuronal damage, and the activation status of inflammation. Despite inherent limitations, this research provides pivotal insights into the intricate interplay between SARS‐CoV‐2 and the CNS, underscoring the necessity for ongoing research to fully comprehend the virus's enduring effects on the CNS. The findings underscore the urgency of continuous investigation Neuro‐COVID to unravel the complexities of this relationship, and pivotal in addressing the long‐term consequences of COVID‐19 on neurological health.

Developing advanced sorbents for selective carbon dioxide (CO2) sequestration with minimal energy consumption remains a pivotal challenge. This study presents a novel strategy through transforming 3D bulk zirconium-porphyrin frameworks into the corresponding 2D nanosheet-assembled superstructures for enhanced CO2 capture. The hierarchical frameworks with well-organized nanosheet architectures exhibit significantly increased specific surface area from 600 m2/g to 2400 m2/g while providing kinetic benefits for gas diffusion. Compared to the adsorption behavior of the bulk counterparts, the nanosheet-assembled frameworks demonstrate a 1.5-fold increase in CO2 adsorption capacity without compromising CO2/N2 selectivity. Theoretical calculation reveals that the coordination unsaturated Zr-O clusters, electron delocalized environments both in interlayer gaps and micropores provided binding sites for CO2 capture. Our research demonstrates an adaptable structure-directed approach for the crystal engineering of metal-organic frameworks which would inspire the creation of state-of-the-art crystalline porous materials for broadened applications.

Abstract Human norovirus (HuNoV) is the leading cause of nonbacterial acute gastroenteritis, which is highly infectious, rapidly evolving, and easily transmitted through feces. The accurate and early detection of HuNoV subtypes is essential for effective treatment, early surveillance, risk assessment, and disease prevention. In this study, a portable multiplex HuNoV detection platform that combines integrated microfluidics and cascade isothermal amplification, using a streamlined protocol for clinical fecal‐based diagnosis is presented. To overcome the problems of carryover contamination and the incompatibility between recombinase polymerase amplification (RPA) and loop‐mediated isothermal amplification (LAMP), a Dynamic confined‐space‐implemented One‐pot RPA‐LAMP colorimetric detection system (DORLA) is developed by creating a hydrogen bond network. The DORLA system exhibits excellent sensitivity, with detection limits of 10 copies µL−1 and 1 copy µL−1 for HuNoV GI and GII, respectively. In addition, a portable diagnostic platform consisting of a thermostatic control module and an integrated 3D‐printed microfluidic chip for specific HuNoV capture, nucleic acid pretreatment, and DORLA detection, which enables simultaneous diagnosis of HuNoV GI and GII is developed. A DORLA‐based microfluidic platform exhibits satisfactory performance with high sensitivity and portability, and has high potential for the rapid point‐of‐care detection of HuNoV in clinical fecal samples, particularly in resource‐limited settings.

Helicobacter pylori infection is associated with the risk of gastrointestinal (GI) cancers; however, its impact on immunotherapy for GI cancers remains uncertain. In this study, we included 10,122 patients who underwent 13C-urea breath tests. Among 636 patients with Epstein-Barr virus–negative microsatellite-stable gastric cancer (GC) who were treated with anti-PD-1/PD-L1 therapy, H. pylori–positive patients exhibited significantly longer immune-related progression-free survival (irPFS) compared with H. pylori–negative patients (6.97 months versus 5.03 months, p

Electron cyclotron harmonic (ECH) waves are electrostatic emissions frequently observed in the Earth’s magnetosphere. By precipitating magnetospheric hot electrons into the ionosphere, ECH waves play a critical role in the formation of diffuse aurora. Previous research has extensively investigated the strong dependence of ECH waves on the geomagnetic activities. In this study, we present the first report of the prompt response of ECH waves to an interplanetary shock on the basis of WIND and Van Allen Probes observations. Our observations and analyses demonstrate that the interplanetary shock compression can increase >0.1 keV hot electron fluxes in the dayside inner magnetosphere, consequently leading to the prompt intensification of ECH waves by promoting the wave instability. These findings expand our comprehension of the impacts of solar wind disturbances on magnetospheric plasma waves and offer fresh insights into solar wind-magnetosphere-ionosphere coupling.

Abstract Background Large language models (LLMs) are emerging artificial intelligence (AI) technology refining research and healthcare. Their use in medicine has seen numerous recent applications. One area where LLMs have shown particular promise is in the provision of medical information and guidance to practitioners. Objective This study aims to assess three prominent LLMs—Google’s AI BARD, BingAI and ChatGPT‐4 in providing management advice for melanoma by comparing their responses to current clinical guidelines and existing literature. Methods Five questions on melanoma pathology were prompted to three LLMs. A panel of three experienced Board‐certified plastic surgeons evaluated the responses for reliability using reliability matrix (Flesch Reading Ease Score, the Flesch–Kincaid Grade Level and the Coleman–Liau Index), suitability (modified DISCERN score) and comparing them to existing guidelines. T‐test was performed to calculate differences in mean readability and reliability scores between LLMs and p value 0.05). Suitability‐wise using DISCERN score, ChatGPT 58 (±6.44) significantly (p = 0.04) outperformed BARD 36.2 (±34.06) and was insignificant to BingAI's 49.8 (±22.28). Conclusion This study demonstrates that ChatGPT marginally outperforms BARD and BingAI in providing reliable, evidence‐based clinical advice, but they still face limitations in depth and specificity. Future research should improve LLM performance by integrating specialized databases and expert knowledge to support patient‐centred care.

BackgroundStreptococcus pneumoniae is a common pathogen that colonizes the human upper respiratory tract, causing high morbidity and mortality worldwide. This study aimed to investigate the prevalence status of S. pneumoniae isolated from patients of all ages in Southwest China, including serotype, antibiotic susceptibility and other molecular characteristics, to provide a basis for clinical antibiotic usage and vaccine development.MethodsThis study was conducted from January 2018 to March 2022 at West China Hospital, West China Second University Hospital, First People’s Hospital of Longquanyi District (West China Longquan Hospital), Meishan Women and Children’s Hospital (Alliance Hospital of West China Second University Hospital) and Chengdu Jinjiang Hospital for Women and Children Health. Demographic and clinical characteristics of 263 pneumococcal disease (PD) all-age patients were collected and analyzed. The serotypes, sequence types (STs), and antibiotic resistance of the strains were determined by next-generation sequencing, sequence analysis and the microdilution broth method.ResultsThe most common pneumococcal serotypes were 19F (17.87%), 19A (11.41%), 3 (8.75%), 23F (6.46%) and 6A (5.70%). Coverage rates for PCV10, PCV13, PCV15, PCV20 and PCV24 were 36.12, 61.98, 61.98, 63.12 and 64.26%, respectively. Prevalent STs were ST271 (12.55%), ST320 (11.79%), ST90 (4.18%), ST876 (4.18%) and ST11972 (3.42%). Penicillin-resistant S. pneumoniae (PRSP) accounted for 82.35 and 1.22% of meningitis and nonmeningitis PD cases, respectively. Resistance genes msrD (32.7%), mefA (32.7%), ermB (95.8%), tetM (97.3%) and catTC (7.6%) were found among 263 isolates. Most isolates showed high resistance to erythromycin (96.96%) and tetracycline (79.85%), with more than half being resistant to SXT (58.94%). A few isolates were resistant to AMX (9.89%), CTX (11.03%), MEN (9.13%), OFX (1.14%), LVX (1.14%) and MXF (0.38%). All isolates were susceptible to vancomycin and linezolid.ConclusionOur study provides reliable information, including the prevalence, molecular characterization and antimicrobial resistance of S. pneumoniae isolates causing pneumococcal diseases in Southwest China. The findings contribute to informed and clinical policy decisions for prevention and treatment.

In this study, we systematically investigated the interactions between Cu2+ and various biomolecules, including double-stranded DNA, Y-shaped DNA nanospheres, the double strand of the hybridization chain reaction (HCR), the network structure of cross-linked HCR (cHCR), and small molecules (PPi and His), using Cu2+ as an illustrative example. Our research demonstrated that the coordination between Cu2+ and these biomolecules not only is suitable for modulating luminescent material signals through complexation reactions with Cu2+ but also enhances signal intensities in materials based on chemical reactions by increasing spatial site resistance and local concentration. Building upon these findings, we harnessed the potential for signal amplification in self-assembled DNA nanospheres and the selective complexation modulation of calcein in conjunction with the aptamer targeting mucin 1 as a recognition probe. We applied this approach to the analysis of circulating tumor cells, with the lung cancer cell line A549 serving as a representative model. Our assay, utilizing both a fluorometer and a handheld detector, achieved impressive detection limits of ag/ml and single-cell levels for mucin 1 and A549 cells, and this approach was successfully validated using 46 clinical samples, yielding 100% specificity and 86.5% sensitivity. Consequently, our strategy has paved the way for more portable and precise disease diagnosis.