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Abstract We explore the decay of bound neutrons in the JUNO liquid scintillator detector into invisible particles (e.g., $$n\rightarrow 3 \nu $$ n → 3 ν or $$nn \rightarrow 2 \nu $$ n n → 2 ν ), which do not produce an observable signal. The invisible decay includes two decay modes: $$ n \rightarrow { inv} $$ n → inv and $$ nn \rightarrow { inv} $$ n n → inv . The invisible decays of s-shell neutrons in $$^{12}\textrm{C}$$ 12 C will leave a highly excited residual nucleus. Subsequently, some de-excitation modes of the excited residual nuclei can produce a time- and space-correlated triple coincidence signal in the JUNO detector. Based on a full Monte Carlo simulation informed with the latest available data, we estimate all backgrounds, including inverse beta decay events of the reactor antineutrino $${\bar{\nu }}_e$$ ν ¯ e , natural radioactivity, cosmogenic isotopes and neutral current interactions of atmospheric neutrinos. Pulse shape discrimination and multivariate analysis techniques are employed to further suppress backgrounds. With two years of exposure, JUNO is expected to give an order of magnitude improvement compared to the current best limits. After 10 years of data taking, the JUNO expected sensitivities at a 90% confidence level are $$\tau /B( n \rightarrow { inv} ) > 5.0 \times 10^{31} \, \textrm{years}$$ τ / B ( n → inv ) > 5.0 × 10 31 years and $$\tau /B( nn \rightarrow { inv} ) > 1.4 \times 10^{32} \, \textrm{years}$$ τ / B ( n n → inv ) > 1.4 × 10 32 years .

Abstract Asparagine endopeptidase (AEP) is ubiquitously expressed in both physiological and pathological contexts, yet its precise role and functional mechanism in breast cancer remain elusive. Here, we identified increased AEP expression in breast cancer tissues, which correlated with poorer survival rates and a propensity for lung metastasis among breast cancer patients. Loss of AEP impaired colony formation by breast cancer cells in vitro and suppressed lung metastasis in mice. By Gene Set Enrichment Analysis (GSEA) analysis, we uncovered a positive association between aberrant AEP expression and autophagy as well as lysosomal function. Loss of AEP in breast cancer cells led to reduced autophagosome clearance and impaired lysosomal degradation. Mechanically, by co-immunoprecipitation and in vitro enzymatic cleavage assays, we identified the regulatory subunit p85 of class IA PI3K phosphatidylinositol 3-kinase (PI3K), as a substrate of AEP. Loss of AEP led to elevated endo/lysosomal PI3K activity and subsequent conversion of PtdIns(4,5)P2 (PIP2) to PtdIns(3,4,5)P3 (PIP3) on endo/lysosome membranes. Notably, the novel function of endo/lysosomal PI3K which was differently with its role in cytomembrane, was revealed by pharmacological inhibition with a potent endo/lysosomal PI3K inhibitor PIK75. PIK75 treatment showed increased vacuolar-ATPase assembly endo/lysosome membranes, prevented over lysosome perinuclear clustering/fusion and enhanced autophagosome clearance. Our findings demonstrate that AEP regulates cellular autophagy by modulating lysosomal function through its control over endo/lysosomal PI3K activity. These results suggest that AEP may serve as a potential target for suppressing metabolic adaptations in cancer.

Abstract Background Advance care planning is an important part of palliative care. Public acceptance is a prerequisite for the widespread development and implementation of advance care planning. However, little is known about the level of public’s acceptance and influencing factors of advance care planning across different life cycles. Methods A cross-sectional study in mainland China was conducted from June 20 to August 31, 2022. We used multi-stage sampling strategy to recruit participators. A stepwise linear regression analysis was used to examine the influencing factors in different life cycles (nonage, mature age, middle age and old age). Results The final sample size was 18,002. The average acceptance score of advance care planning of the public throughout the entire life cycle was 64.03. The average score in nonage was 67.13, which is the highest. The average score in mature age was 63.87, in middle age was 63.51, and in old age was 63.54. Multiple linear stepwise regression results indicated that death education support level, well-being index, neighbor relations, health literacy, family social status, and siblings were influencing factors in nonage. Medical insurance, injury events, multiple properties, death education support level, health literacy, family social status, neighbor relation, social support, family health, media contact, and well-being index were influencing factors in mature age. In middle age, region, living alone, depression, debt, houses, death education support level, health literacy, social support, and family social status were influencing factors. In old age, injury event, death education support level, neighbor relation, well-being index, siblings and children were influencing factors. Conclusions This study is the first to compare the Chinese people with different life cycles. It found that the public’s acceptance and influencing factors of advance care planning varied across different life cycles. Governments and health care personnel should emphasize autonomy and initiate advance care planning based on different life cycles and individual approaches, then introduce appropriate public health policies into newer and broader fields.

To rapidly develop hyper-stable inhibitors that bind specifically and covalently to functional proteins is critical for diagnostics and therapeutics. Taking targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants as an example, we report a fast and low-cost de novo design strategy on covalent bonding peptides toward the SARS-CoV-2 spike protein receptor-binding domain (RBD), hence blocking its interaction with the human angiotensin-converting enzyme 2 (hACE2). As a proof-of-concept, peptide scaffolds built by ligating the hotspot residues at the hACE2-Omicron RBD interface were docked against RBD, and then the chemically modified peptides were designed by predicting their reactivity against RBD using a modified Amber ff14SB force field. Two peptides (15- and 16-mer peptides) were equipped with sulfonyl fluoride warheads bound with the conserved Y449 residue of RBD via the sulfur (VI) fluoride exchange (SuFEx) click chemistry. With permanent bonding and without dissociation, the two peptides blocked Omicron BA.2 pseudovirus infection with 50% inhibitory concentration (IC50) values of 1.07 μM and 1.56 μM, respectively. Our design approach greatly promotes the discovery of hyper-stable inhibitors against SARS-CoV-2 variants and other rapidly evolving viruses, potentially applicable to combat future viral outbreaks efficiently.

Obesity, caused by excessive energy, leads to body weight gain and various diseases, including cognitive impairment. Current studies suggest that diet restriction such as optimal fasting and regular exercise are crucial for improving cognitive capacity. However, further exploration is needed to understand the specific mechanisms of high fat diet (HFD)-induced cognitive decline in obesity. In the present study, 4-month-old mice were subjected to HFD feeding for 18 weeks, followed by aerobic exercise and high-intensity intermittent exercise, regular diet feeding, and intermittent fasting for 8 weeks, and then used to evaluate cognitive capacity, inflammation, compromised insulin signaling pathway, and apoptosis in hippocampal tissue, as well as AMPK/SIRT1 and TLR4 signal pathways. Obese mice revealed impaired cognitive capacity as compared with mice fed with regular diets. In contrast, aerobic exercise, high-intensity intermittent exercise, regular diet, and intermittent fasting could inhibit apoptosis caused by inflammation-mediated compromised insulin signaling pathway in hippocampal tissues through activating the AMPK/SIRT1 signal pathway and suppressing the TLR4 signal pathway, thereby rescuing the cognitive impairment of obese mice. Therefore, diet restriction and exercise interventions may play a positive role in reverting obesity-induced cognitive impairment.

Abstract Background Wheat is one of major sources of human cadmium (Cd) intake. Reducing the grain Cd concentrations in wheat is urgently required to ensure food security and human health. In this study, we performed a field experiment at Wenjiang experimental field of Sichuan Agricultural University (Chengdu, China) to reveal the effects of FeCl3 and Fe2(SO4)3 on reducing grain Cd concentrations in dwarf Polish wheat (Triticum polonicum L., 2n = 4x = 28, AABB). Results Soil application of FeCl3 and Fe2(SO4)3 (0.04 M Fe3+/m2) significantly reduced grain Cd concentration in DPW at maturity by 19.04% and 33.33%, respectively. They did not reduce Cd uptake or root-to-shoot Cd translocation, but increased Cd distribution in lower leaves, lower internodes, and glumes. Meanwhile, application of FeCl3 and Fe2(SO4)3 up-regulated the expression of TpNRAMP5, TpNRAMP2 and TpYSL15 in roots, and TpYSL15 and TpZIP3 in shoots; they also downregulated the expression of TpZIP1 and TpZIP3 in roots, and TpIRT1 and TpNRAMP5 in shoots. Conclusions The reduction in grain Cd concentration caused by application of FeCl3 and Fe2(SO4)3 was resulted from changes in shoot Cd distribution via regulating the expression of some metal transporter genes. Overall, this study reports the physiological pathways of soil applied Fe fertilizer on grain Cd concentration in wheat, suggests a strategy for reducing grain Cd concentration by altering shoot Cd distribution.

Abstract Delayed neurocognitive recovery after surgery is associated with increased morbidity and mortality. However, its mechanism of action remains controversial and complex. A prospective, double‐blind, randomized controlled trial was performed at the Affiliated Hospital of Zunyi Medical University. Older patients (aged 65 years and older) who underwent gastrointestinal surgery were randomly divided into sevoflurane‐based or propofol‐based anesthesia groups. The Mini‐Mental State Examination was performed to evaluate cognitive function. Peripheral venous blood was collected to test the levels of choline acetyltransferase and acetylcholinesterase. A total of 75 patients were enrolled and 30 patients in each group completed the study. On Day 1 postoperation, patients in the sevoflurane group showed worse performance on the Mini‐Mental State Examination than patients in the propofol group. Lower blood choline acetyltransferase concentrations and higher acetylcholinesterase concentrations were observed in patients who had sevoflurane anesthesia than in patients who had propofol anesthesia 1 day postoperative. At 3 days postoperation, patients with sevoflurane‐ or propofol‐based general anesthesia did not differ regardless of Mini‐Mental State Examination score or choline acetyltransferase and acetylcholinesterase levels. Sevoflurane‐based anesthesia has short‐term delayed neurocognitive recovery in older surgical patients, which may be related to central cholinergic system degeneration.

Abstract Background This study investigates the effectiveness of a self-developed intelligent monitoring system for home-based knee rehabilitation following total knee arthroplasty (TKA). Methods In this randomized controlled trial, 120 patients undergoing TKA were divided using random digit allocation. Preoperative and one-month postoperative assessments of knee function, quality of life, and isometric knee extension strength were conducted with the Intelligent Monitoring System. Patients received group-specific rehabilitation instructions pre-discharge and performed exercises for one month. Results Changes in isometric knee extensor strength on the affected side within one month post-surgery for the brace-monitored rehabilitation group showed a significant decrease three days after surgery compared to one day before surgery. Subsequent measurements taken at postoperative days 5, 7, 14, and 21 indicated a gradual increase in strength, although these increases did not reach statistical significance when compared with previous measurements. One month post-surgery, all groups demonstrated significant improvements in knee joint function and mobility compared to pre-surgery levels. Notably, the brace-monitored group showed statistically significant improvements in 36-Item Short-Form Health Survey (SF-36) scores over the conventional rehabilitation group. Conclusions The Intelligent Monitoring System provides effective real-time monitoring and guidance for home-based knee rehabilitation post-TKA. It significantly enhances knee joint function, isometric knee extension strength, and quality of life shortly after surgery compared to traditional rehabilitation methods. This system offers a promising approach for improving postoperative recovery in TKA patients. Trial registration This study was approved by the Medical Ethics Committee of Xiangya Hospital, Central South University (Ethics Approval Number 202209008-2). It was registered with the China Clinical Trial Registry, a primary registry of the World Health Organization’s International Clinical Trials Registry Platform (Registration Number ChiCTR2300068852).

ABSTRACT Background Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder characterized by dysfunction of motile cilia. While approximately 50 genes have been identified, around 25% of PCD patients remain genetically unexplained; elucidating the pathogenicity of specific variants remains a challenge. Methods Whole exome sequencing (WES) and Sanger sequencing were conducted to identify potential pathogenic variants of PCD. Minigene assays were performed to evaluate the pathogenicity of variants. Transmission electron microscopy (TEM) and high‐speed video analysis (HSVA) were conducted to analyze the function of cilia in respiratory epithelial cells. Results We identified two variants of DNAAF3: c.557G>A, p.G186E in exon 5, and c.1364G>A, p.G455D at the terminal nucleotide of exon 10 in a 16‐year‐old male patient. Through a minigene assay, we demonstrated that the c.1364G>A variant led to a four‐nucleotide skipping. The cilia in epithelial ciliary cells of the proband were almost immotile. The absence of outer dynein arms and inner dynein arms was also observed. Conclusions Our study identified two compound heterozygous variants of DNAAF3, a pathogenic gene for PCD, and proved that a novel missense variant c.1364G>A affects splicing. Our findings not only expanded the spectrum of mutations in the DNAAF3 gene but also highlighted the importance of investigating variants of uncertain significance (VUS) for comprehensive genetic diagnoses.

Summary: Efficient prime editor (PE) delivery in vivo is critical for realizing its full potential in disease modeling and therapeutic correction. Although PE has been divided into two halves and delivered using dual adeno-associated viruses (AAVs), the editing efficiency at different gene loci varies among split sites. Furthermore, efficient split sites within Cas9 nickase (Cas9n) are limited. Here, we verified that 1115 (Asn) is an efficient split site when delivering PEs by dual AAVs. Additionally, we utilized a feature in which reverse transcriptase could be detached from the Cas9n and designed split sites in the first half of Cas9n. We found that split-PE-367 enabled high editing efficiency with Rma intein. To test the editing efficiency in vivo, split-ePE3-367 was packaged in AAV9 and achieved 17.5% precise editing in mice. Our findings establish an alternative split-PE architecture that enables robust editing efficiency, facilitating potential utility in disease modeling and correction.

Oral cancer is a highly malignant disease characterized by recurrence, metastasis, and poor prognosis. Autophagy, a catabolic process induced under stress conditions, has been shown to play a dual role in oral cancer development and therapy. Recent studies have identified that autophagy activation in oral epithelial cells suppresses cancer cell survival by inhibiting key pathways such as the mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK), while activating the adenosine monophosphate-activated protein kinase (AMPK) pathway. Inducing autophagy promotes degradation of eukaryotic initiation factor 4E, thus reducing metastasis and enhancing the efficacy of chemotherapy, radiotherapy, and immunotherapy. Furthermore, autophagy induction can modulate the tumor immune microenvironment and enhance antitumor immunity. This review comprehensively summarizes the relationship between autophagy and oral cancer, focusing on its mechanisms and therapeutic potential when combined with conventional treatments. While promising, the precise mechanisms and clinical applications of autophagy inducers in oral cancer therapy remain to be elucidated, offering new directions for future research to improve treatment outcomes and reduce recurrence.

Abstract Tertiary lymphoid structure (TLS) is associated with various pathologies, including those of cancers and chronic infections. Depending on the organ, multiple factors regulate the formation of TLS. However, the role of TLS in immune response and the molecules that drive its formation remain uncertain. The dental pulp, includes a few immune cells surrounded by rigid mineralized tissue, and opens to the outside through the apical foramen. Owing to this special organization, the dental pulp generates a directional immune response to bacterial infection. Considering this aspect, the dental pulp is an ideal model for comprehensively studying the TLS. In the present study, single‐cell RNA sequencing of healthy and inflamed human dental pulp reveals known markers of TLS, including C‐C motif chemokine ligand 19 (CCL19), lysosome‐associated membrane glycoprotein 3 (LAMP3), CC chemokine receptor 7 (CCR7), and CD86, present in inflamed dental pulp. Compared with the healthy pulp, types and proportions of immune cells increase, along with enhanced cellular communication. Multiple immunofluorescence staining reveals that typical TLS emerges in dental pulp with pulpitis, consistent with the high expression of CC chemokine ligand 3 (CCL3), which may be a key driver of TLS formation. Moreover, TLS is also observed in a mouse model of pulpitis. These findings collectively offer insights into the formation and function of TLS in response to infection.

Nuclear de-excitations associated with neutrino-nucleus interactions and nucleon decays are playing an increasingly significant role in neutrino experiments. We explore the GEMINI++ code and estimate its ability to account for the de-excitation processes of highly excited 11B⁎ and 15N⁎, which can be created in the liquid scintillator and water Cherenkov detectors respectively. It is found that GEMINI++ can not describe the nuclear experimental data of 11B⁎ and 15N⁎ well. To improve its performance for de-excitations of light nuclei, we modify GEMINI++ and then develop a code of GEMINI++4ν, which can give the best predictions compared with experimental measurements among some widely used statistical model codes.

We present a novel approach to predicting the pressure and flow rate of flexible electrohydrodynamic pumps using the Kolmogorov–Arnold Network. Inspired by the Kolmogorov–Arnold representation theorem, KAN replaces fixed activation functions with learnable spline-based activation functions, enabling it to approximate complex nonlinear functions more effectively than traditional models like Multi-Layer Perceptron and Random Forest. We evaluated KAN on a dataset of flexible EHD pump parameters and compared its performance against RF, and MLP models. KAN achieved superior predictive accuracy, with Mean Squared Errors of 12.186 and 0.012 for pressure and flow rate predictions, respectively. The symbolic formulas extracted from KAN provided insights into the nonlinear relationships between input parameters and pump performance. These findings demonstrate that KAN offers exceptional accuracy and interpretability, making it a promising alternative for predictive modeling in electrohydrodynamic pumping.

Human periodontal ligament stem cells (hPDLSCs) play a critical role in the regeneration of periodontal tissue. Forkhead box protein A1 (FOXA1) has been implicated in the inflammatory mechanisms of various diseases. However, the role of FOXA1 in periodontal inflammation and its effect on the osteogenic differentiation of hPDLSCs remains unclear. In this study, healthy tooth root-derived hPDLSCs were isolated, and flow cytometry was used to detect cell surface markers. Western blot and immunofluorescence analyses were performed to assess FOXA1 levels in different tissues. The levels of inflammatory factors were measured using Western blot and ELISA kits. Alkaline phosphatase (ALP) staining, alizarin red S staining, and Western blot were employed to evaluate the impact of FOXA1 silencing on the osteogenic differentiation of hPDLSCs. Finally, the protein levels in the Toll-like receptor 4 (TLR4)/Myeloid differentiation factor-88 (MyD88)/NF-κB pathway were analyzed using Western blot. Results showed that periodontal membrane tissues from patients with periodontitis exhibited a marked increase in FOXA1 levels. Lipopolysaccharide (LPS) treatment significantly upregulated FOXA1 expression in hPDLSCs, elevated inflammatory factor levels, and inhibited osteogenic differentiation. However, silencing FOXA1 mitigated the effects of LPS. Furthermore, LPS treatment activated the TLR4/MyD88/NF-κB pathway, while FOXA1 silencing impeded this activation. Notably, the application of the TLR4 agonist CRX-527 reversed the inhibitory effects of FOXA1 silencing on LPS-induced responses. In summary, silencing FOXA1 reduced cellular inflammation by inhibiting the TLR4/MyD88/NF-κB pathway and alleviated the suppressive effects of LPS on the osteogenic differentiation of hPDLSCs.

This study has employed 16S rDNA analysis to elucidate the characteristics of the microbial community in the surroundings, facilities, and meat samples collected from a pork wholesale market with the aim of revealing bacterial contamination. In addition, the efficacy of sodium hypochlorite disinfectant was assessed by comparing the bacterial communities in the viable samples before and after disinfection. The bacterial abundances in meat, chopping boards, and knives were positively correlated (r > 0.95, p

Abstract Background This systematic study aims to assess the global epidemiologic, economic, and humanistic burden of illness associated with all types of hereditary angioedema. Methods A systematic search for articles reporting the epidemiologic, economic, and humanistic burden associated with patients with HAE was conducted using English and Chinese literature databases from the inception to May 23, 2022. The selected studies were assessed for their quality and risk of bias. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022352377). Results In total, 65 articles that met the search inclusion criteria reported 10,310 patients with HAE, of whom 5861 were female patients. Altogether, 4312 patients (81%) and 479 patients (9%) had type 1 and type 2 HAE, respectively, whereas 422 patients (8%) had HAE-normal C1-INH. The overall prevalence of all types of HAE was between 0.13 and 1.6 cases per 100,000. The mean or median delay from the first onset of a symptom of HAE to confirmed diagnosis ranged from 3.9 to 26 years. The estimated risk of death from asphyxiation was 8.6% for patients with HAE. Hospitalization, medication, unnecessary surgeries, doctor visits, specialist services, and nursing costs are direct expenses that contribute to the growing economic burden. The indirect cost accounted mostly due to missing work ($3402/year) and loss of productivity ($5750/year). Furthermore, impairment of QoL as reported by patient-reported outcomes was observed. QoL measures identified depression, anxiety, and stress to be the most common symptoms for adult patients and children. Conclusion This study highlights the importance of early diagnosis and the need for improving awareness among health care professionals to reduce the burden of HAE on patients and society.

Abstract Tumor-draining lymph nodes (TDLNs) are usually the first station of tumor metastasis in lung cancer. TDLNs+ have distinct pathomorphologic and tumor microenvironment (TME)-compositional patterns, which still need to be thoroughly investigated in lung adenocarcinoma (LUAD). Here, we enrolled 312 LUAD patients with TDLNs+ from our institution between 2015 and 2019. 3DHISTECH was used to scan all of the TDLNs+. Based on morphologic features, TDLNs+ patterns were classified as polarized-type or scattered-type, and TME-compositional patterns were classified as colloid-type, necrosis-type, specific-type, and common-type. Multivariate analysis revealed an increased risk of early recurrence associated with scattered-type (HR 2.37, 95% CI: 1.06–5.28), colloid-type (HR 1.95, 95% CI: 1.03–3.67), and necrosis-type (HR 2.21, 95% CI: 1.13–4.89). NanoString transcriptional analysis revealed an immunosuppression and vascular invasion hallmark in scattered and necrosis patterns and an immunoactivated hallmark in polarized and common patterns. According to imaging mass cytometry (IMC), the scattered and necrosis patterns revealed that germinal centers (GC) were compromised, GCB cell and T cell proliferation were deficient, tumor cells had the potential for proliferation, and the immune attack may be weaker. In this study, we present evidence that LUAD patients have distinct patterns and immune hallmarks of TDLNs+ related to their prognosis.

Abstract Background Syntaxin6 (STX6) is a SNARE (Soluble N-ethylmaleimide-sensitive factor attachment protein receptors) protein complex located in the trans-Golgi network and endosomes, which is closely associated with a variety of intracellular membrane transport events. STX6 has been shown to be overexpressed in a variety of human malignant tumors such as esophageal, colorectal, and renal cell carcinomas, and participates in tumorigenesis and development. Methods Based on clinical public database and clinical liver samples analysis, the expression of STX6 in hepatocellular carcinoma (HCC) tissues was investigated. The effects of STX6 on proliferation, migration and invasion of HCC cell in vitro and in vivo were evaluated through gain- and loss-of-function studies. We further performed RNA-seq analysis and protein interactome analysis, to further decifer the detailed mechanisms of STX6 in the regulation of the JAK-STAT pathway in HCC. Results STX6 expression was upregulated in HCC tissues and its expression was highly correlated with the high histological grade of the tumor. STX6 promoted HCC cell proliferation, migration and invasion both in vitro and in vivo. Mechanistically, STX6 mediated tumor progression depending on promoting the activation of JAK-STAT signaling pathway. Receptor for activated protein kinase C (RACK1) as an essential adaptor protein mediating STX6 regulation of JAK-STAT pathway. Specifically, STX6 interacted with RACK1 and then recruited signal transducer and activator of transcription 3 (STAT3) to form a protein-binding complex and activates STAT3 transcriptional activity. Conclusions This study provided a novel concept that STX6 exerted oncogenic effects by activating the STAT3 signaling pathway, and STX6 might be a promising therapeutic target for HCC.

Abstract Background Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive disorder affecting the white matter of the brain. It typically manifests during childhood, with clinical features including sudden and severe neurological deterioration triggered by stressors such as febrile illness, minor head trauma, or stressful events. Adult-onset cases of VWM are exceptionally uncommon. Case presentation In this case, we present an adult patient who exhibited late-onset progressive VWM characterized by ataxia, postural instability, cognitive impairment, and emotional disturbances. Comprehensive screening for endocrine, metabolic, tumor, and immunologic disorders yielded normal or negative results. Brain imaging revealed diffuse and confluent hyperintensity in the white matter on T2-weighted images, along with periventricular cavitations. Genetic testing confirmed the diagnosis of VWM, identifying two heterozygous variants in the eukaryotic translation initiation factor 2B subunit γ (EIF2B3) gene: a pathogenic variant, c.1037 T > C (p.I346T), and a variant of undetermined significance, c.22A > T (p.M8L). Upon a 2-year follow-up, the patient's symptoms deteriorated rapidly following a COVID-19 infection. Conclusions In conclusion, we have presented a case of classical adult-onset VWM. Since there are no cures or definitive treatments for the disease, it's extremely important to focus on early diagnosis and the prevention of stressors to avoid acute deterioration.

Abstract Background Chronic enteropathy associated with SLCO2A1 gene (CEAS) results from loss-of-function variants in SLCO2A1, which encodes the prostaglandin transporter (PGT). CEAS follows an autosomal recessive inheritance pattern. To date, approximate 30 pathogenic variants have been reported in CEAS. Methods We performed whole exome sequencing (WES) to screen for potential pathogenic variants in a patient suspected of having CEAS, and confirmed a variant in SLCO2A1 using Sanger sequencing. We established an in vitro minigene model to compare splicing between wild type (WT) and mutant transcripts. Quantitative polymerase chain reaction (qPCR) was used to evaluate SLCO2A1 transcription in the stomach and colon tissues from the patient and a healthy control (HC). The transcripts were further cloned and sequenced. Results The patient had a novel, homozygous, recessive c.929A > G variant in exon 7 of SLCO2A1, which has not been previously reported in CEAS or PHO. This variant altered splicing, resulting in an exon 7‐truncated transcript lacking 16 bases. No normal transcript was detected in the patient’s stomach or colon tissue. qPCR also showed significantly decreased SLCO2A1 transcription compared to HC. Conclusion A previously unreported variant caused defective SLCO2A1 splicing and reduced mRNA levels in a patient with CEAS and PHO. This research enhances understanding of CEAS and PHO pathophysiology and aids genetic counseling and diagnosis.

Abstract Objective Abnormalities in the gray matter structure of cerebral small vessel disease (CSVD) have been observed throughout the brain. However, whether cortico‐cortical connections exist between regions of gray matter atrophy in patients with CSVD has not been fully elucidated. This question was tested by comparing the gray matter covariance networks in CSVD patients with and without cognitive impairment (CI). Methods We performed multivariate modeling of the gray matter volume measurements of 61 patients with CI (CSVD‐CI), 85 patients without CI (CSVD‐NC), and 108 healthy controls using source‐based morphological analysis (SBM) to obtain gray matter structural covariance networks at the population level. Then, correlations between structural covariance networks and cognitive functions were analyzed in CSVD patients. Finally, a support vector machine (SVM) classifier was used with the gray matter covariance network as a classification feature to identify CI among the CSVD population. Results The results of the analysis of all the subjects showed that compared with healthy controls, the expression of the thalamic covariance network, cerebellum covariance network, and calcarine cortex covariance network was reduced in patients with CSVD. Moreover, CSVD‐CI patients showed a significant reduction in the expression of the thalamic covariance network, encompassing the thalamus and the parahippocampal gyrus, relative to CSVD‐NC patients, which persisted after excluding CSVD patients with thalamic lacunes. In patients with CSVD, cognitive functions were positively correlated with measures of the thalamic covariance network. More than 80% of CSVD patients with CI were correctly identified by the SVM classifier. Interpretation Our findings provide new evidence to explain the distribution state of gray matter reduction in CSVD patients, and the thalamic covariance network is the core region for early gray matter reduction during the development of CSVD disease, which is related to cognitive deficits. Reduced expression of thalamic covariance networks may provide a neuroimaging biomarker for the early identification of cognitive impairment in CSVD patients.

Abstract Ovarian cancer is a major gynecological cancer that has poor prognosis associated mainly to its late diagnosis. Cisplatin is an FDA approved ovarian cancer therapy and even though the therapy is initially promising, the patients mostly progress to resistance against cisplatin. The underlying mechanisms are complex and not very clearly understood. Using two different paired cell lines representing cisplatin-sensitive and the cisplatin-resistant ovarian cancer cells, the ES2 and the A2780 parental and cisplatin-resistant cells, we show an elevated proto-oncogene c-Myb in resistant cells. We further show down-regulated lncRNA NKILA in resistant cells with its de-repression in resistant cells when c-Myb is silenced. NKILA negatively correlates with cancer cell and invasion but has no effect on cellular proliferation or cell cycle. C-Myb activates NF-κB signaling which is inhibited by NKILA. The cisplatin resistant cells are also marked by upregulated stem cell markers, particularly LIN28A and OCT4, and downregulated LIN28A-targeted let-7 family miRNAs. Whereas LIN28A and downregulated let-7s individually de-repress c-Myb-mediated cisplatin resistance, the ectopic expression of let-7s attenuates LIN28A effects, thus underlying a c-Myb-NKILA-LIN28A-let-7 axis in cisplatin resistance of ovarian cancer cells that needs to be further explored for therapeutic intervention.

Objective To study the changes in related parameters after secondary preparation of blood components, in order to further improve the quality of blood components. Methods Different centrifugation conditions were selected for the preparation of primary blood component red blood cells in additive solution leukocytes reduced, and the quality was tested. Then, using the red blood cells in additive solution leukocytes reduced as the initial blood for secondary preparation, and the red blood cells were washed through the Haemonetics ACP 215 device, and the quality was tested. The preparation parameters of blood components were observed, compared and optimized. Results Under comparable centrifugation effects of different centrifugation conditions, the quality control items, which of primary blood components of red blood cells in additive solution leukocytes reduced and frozen plasma prepared by the separation, such as volume, hemoglobin, hematocrit and residual white blood cells met the relevant national standards. And the quality control items of secondary blood components of washed red blood cells such as the hemoglobin and superalbumin content both met the relevant national standards, while volume exceeded the standard by 7-14 mL, which can be operated to the standard range. In addition, the recovery rate of red blood cells and the clearance rate of plasma protein could reach 75% and 99% respectively. Conclusion There is a certain correlation between primary and secondary preparation of blood components, but the relevant parameters of secondary preparation of blood components can be flexibly adjusted according to the actual situation to ensure that the quality of prepared blood component products meet the national standards, thus ensuring clinical treatment effect and safety.

Abstract We study the geometry of $$T\overline{T }$$ -deformed BTZ black hole and find it can be regarded as a quotient of hyperbolic space. We then consider the massive scalar field propagating in the $$T\overline{T }$$ -deformed BTZ black hole background. The one-loop partition function of scalar field is calculated using the heat kernel method and the Wilson spool proposal. These two methods give consistent result which implies the Wilson spool proposal still holds under $$T\overline{T }$$ deformation. Moreover, we also calculate the one-loop partition function of graviton in $$T\overline{T }$$ -deformed BTZ black hole. We find the deformed one-loop partition functions are modified in a simple way, which corresponds to a replacement of the modular parameter. The result precisely matches the large c expansion of $$T\overline{T }$$ -deformed CFT partition function. These results provide a further check about the correspondence between $$T\overline{T }$$ -deformed CFT2 and AdS3 with mixed boundary condition.

Background: Since the twentieth century, endocrine-disrupting substances (EDCs) such as phthalates and organophosphates have been utilised in various goods. The long-term usage of these products may have negative effects on people's health. Most EDCs are metabolized through kidneys, but there are few research investigating renal damage from exposure to EDCs in the elderly. This study aims to examine the effects of EDCs exposure on renal function in the elderly population. Methods: In this cross-sectional study, a total of 200 elder from a community in northeast China were enrolled. All subjects were investigated by questionnaire, physical examination, and biological sample collection. Estimated glomerular filtration rate (eGFR) was used to classify renal function group. Lasso regression was used to screen out the EDCs related to renal function. After covariate adjustment, binary logistic regression was used to analyze the relationship between decreased renal function and EDCs. Weighted quantile sum (WQS) regression was used to assess the association of combined-EDCs with decreased renal function, subgroup analyses were performed to identify potentially sensitive populations to the effects of EDCs on decreased renal function. Results: Binary logistic regression showed that 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHT-COOH), Mono(3-carboxypropyl) phthalate (MCPP), and Methyl paraben (MeP) were negatively associated with decreased renal function, with odds ratio (OR) and 95% confidence intervals of 0.591 (0.366, 0.954), 0.990 (0.981, 0.999) and 0.997 (0.995, 0.999), respectively. WQS regression found DPP (Weights = 22.5%) to have the greatest effect on decreased renal function in the elderly. Moreover, significant potential interactions were observed among MEHP&MOcP with hypertension on decreased renal function (Pinteraction = 0.014), as well as BPS and MEHP&MocP with Overweight/obesity on decreased renal function (Pinteraction = 0.032, 0.024). Conclusions: BHT-COOH, MCPP, and MeP were negatively associated with decreased renal function in the elderly. Elders with hypertension and who are overweight /obesity may be more sensitive to EDCs.

Multiple embryonic origins give rise to forebrain oligodendrocytes (OLs), yet controversies and uncertainty exist regarding their differential contributions. We established intersectional and subtractional strategies to genetically fate map OLs produced by medial ganglionic eminence/preoptic area (MGE/POA), lateral/caudal ganglionic eminences (LGE/CGE), and dorsal pallium in the mouse brain. We found that, contrary to the canonical view, LGE/CGE-derived OLs make minimum contributions to the neocortex and corpus callosum, but dominate piriform cortex and anterior commissure. Additionally, MGE/POA-derived OLs, instead of being entirely eliminated, make small but sustained contribution to cortex with a distribution pattern distinctive from those derived from the dorsal origin. Our study provides a revised and more comprehensive view of cortical and white matter OL origins, and established valuable new tools and strategies for future OL studies.

Environmental serious games aim to heighten players’ awareness and comprehension of environmental issues, thus fostering pro-environmental decision-making. Research to date has affirmed these games’ effectiveness in enhancing environmental knowledge and abilities, elevating consciousness regarding environmental matters, and promoting pro-environmental behavioral intentions and actions. Nonetheless, a detailed exploration into the precise mechanisms facilitating these impacts remains scarce. Leveraging theories of motivation, cognition, affect, and behavior, this paper outlines four hypothesized mechanisms of influence and introduces an Embodied-Enactive Cognition Model as a novel perspective. It suggests that future research should expand its inquiry into the multifaceted factors that influence pro-environmental decision-making, deepen the comprehension of the intrinsic mechanisms at play, pioneer novel research methodologies, and diversify the array of categories and contextual applications of environmental serious games.

Objective To retrospectively analyze the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) on the progression free survival (PFS) of advanced gastric cancer (GC) and colorectal cancer (CRC). Method We retrospectively collected all the HIPEC data of GC and CRC in the Chongqing University Cancer Hospital from August 2018 to April 2023. Data were extracted from inpatient records and outpatient examination records. The IBM SPSS statistics 23.0 software was used to analyze the data. We mainly compared the PFS of HIPEC cases with that of non-HIPEC cases (both from our center and from the literature). PFS was analyzed with the Kaplan-Meier method. Log Rank (Mantel Cox), Breslow (Generalized Wilcoxon), and Tarone-Ware were used for univariate analyses. Result A total of 342 HIPEC cases were analyzed in this study. Stage IV GC and CRC accounted for 48.5% of the total number of cases. Abdominal pain and distension (47.4%) were the most common side effects from HIPEC. Serious complications were rare (1.8%, including bleeding, perforation, obstruction, and death). The PFS and disease-free survival (DFS) of abdominal malignancy treated with HIPEC were significantly associated with the TNM stage, but not HIPEC numbers nor HIPEC drugs. In stage IV HIPEC cases, adding adjuvant chemotherapy after HIPEC resulted in better PFS. In addition, the association between peritoneal carcinomatosis index (PCI) and PFS of stage IV HIPEC cases was close to significant. Compared with the 33 stage IV (with peritoneal metastases) GC cases without HIPEC in our center from the last 15 years, the PFS of the 56 stage Ⅳ GC cases with HIPEC was not improved significantly (median PFS: 6 ± 2.92 months vs 7 ± 1.63 months for with vs without HIPEC in stage IV GC, respectively; P ≥ 0.05). Compared with the 58 stage IV (with peritoneal metastases) CRC cases without HIPEC in our center from the last 15 years, the PFS of the 86 stage IV CRC cases with HIPEC was not improved significantly either (median PFS: 7 ± 1.68 months vs 7 ± 0.62 months for with vs without HIPEC in stage IV CRC, respectively; P ≥ 0.05). When comparing our HIPEC data with the non-HIPEC data reported by other scholars for the PFS of advanced GC and CRC, the negative results were similar. Conclusion The PFS/DFS of HIPEC cases was associated with the TNM stage, but not with the HIPEC numbers or HIPEC drugs. PCI may be related to the PFS of stage IV HIPEC cases. Adding chemotherapy or targeted therapy after HIPEC may improve the PFS of stage IV cases. HIPEC did not significantly improve the PFS of stage IV GC or CRC cases in our center.

Myeloid sarcoma (MS) occurs in patients with acute myeloid leukemia (AML). In rare cases, MS can represent a form of blast transformation in patients with myeloproliferative neoplasms (MPN), myelodysplastic neoplasms (MDS), or MDS/MPN. The most frequent chromosomal alterations in MS are t(8;21) or inv(16), with other alterations being reported. Cases of MS in Janus kinase 2 (JAK2)-positive MDS with fibrosis are exceedingly rare. Here, we describe such a case. To the best of our knowledge, this is the first report of a JAK2 V617F mutation-positive MDS case occurring concurrently with MS involving the posterior aspect of the left seventh rib. No clear association has been previously demonstrated between the intramedullary AML cytogenetics and extramedullary disease occurrence. Interestingly, samples from the intramedullary MDS and extramedullary mass in this patient presented the same JAK2 V617F mutation. Following a treatment regimen of azacitidine and venetoclax, the patient achieved complete remission. The chest CT scan showed that the seventh posterior rib mass disappeared. This case provides valuable information for the potential future treatment of this disease.

Abstract Ferredoxin‐2 (FDX2) is an electron transport protein required for iron–sulfur clusters biosynthesis. Pathogenic variants in FDX2 have been associated with autosomal recessive FDX2‐related disorder characterized by mitochondrial myopathy with or without optic atrophy and leukoencephalopathy. We described a new case harboring compound heterozygous variants in FDX2 who presented with recurrent rhabdomyolysis with severe episodes affecting respiratory muscle. Biochemical analysis of the patients revealed hyperexcretion of 2‐hydroxyadipic acid, along with previously reported biochemical abnormalities. The proband demonstrated increased lactate and creatine kinase (CK) with increased amount of glucose infusion. Lactate and CK drastically decreased when parenteral nutrition containing high protein and lipid contents with low glucose was initiated. Overall, we described a new case of FDX2‐related disorder and compare clinical, biochemical and molecular findings with previously reported cases. We demonstrated that 2‐hydroxyadipic acid biomarker could be used as an adjunct biomarker for FDX2‐related disorder and the use of parenteral nutrition as a treatment option for the patient with FDX2‐related disorder during rhabdomyolysis episode. Highlights 2‐Hydroxyadipic acid can serve as a potential adjunct biomarker for iron‐sulfur assembly defects and lipoic acid biosynthesis disorders. Parenteral nutrition containing high lipid and protein content could be used to reverse acute rhabdomyolysis episodes in the patients with FDX2‐related disorder.

Abstract Effects of plant diversity on grassland productivity, or overyielding, are found to be robust to nutrient enrichment. However, the impact of cumulative nitrogen (N) addition (total N added over time) on overyielding and its drivers are underexplored. Synthesizing data from 15 multi-year grassland biodiversity experiments with N addition, we found that N addition decreases complementarity effects and increases selection effects proportionately, resulting in no overall change in overyielding regardless of N addition rate. However, we observed a convex relationship between overyielding and cumulative N addition, driven by a shift from complementarity to selection effects. This shift suggests diminishing positive interactions and an increasing contribution of a few dominant species with increasing N accumulation. Recognizing the importance of cumulative N addition is vital for understanding its impacts on grassland overyielding, contributing essential insights for biodiversity conservation and ecosystem resilience in the face of increasing N deposition.

Abstract While phonon anharmonicity affects lattice thermal conductivity intrinsically and is difficult to be modified, controllable lattice defects routinely function only by scattering phonons extrinsically. Here, through a comprehensive study of crystal structure and lattice dynamics of Zintl-type Sr(Cu,Ag,Zn)Sb thermoelectric compounds using neutron scattering techniques and theoretical simulations, we show that the role of vacancies in suppressing lattice thermal conductivity could extend beyond defect scattering. The vacancies in Sr2ZnSb2 significantly enhance lattice anharmonicity, causing a giant softening and broadening of the entire phonon spectrum and, together with defect scattering, leading to a ~ 86% decrease in the maximum lattice thermal conductivity compared to SrCuSb. We show that this huge lattice change arises from charge density reconstruction, which undermines both interlayer and intralayer atomic bonding strength in the hierarchical structure. These microscopic insights demonstrate a promise of artificially tailoring phonon anharmonicity through lattice defect engineering to manipulate lattice thermal conductivity in the design of energy conversion materials.

Immune checkpoint inhibitors (ICIs) are monoclonal antibody antagonists, which can block cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death-1/ligand-1 (PD-1/PD-L1) pathways, and other molecules exploited by tumor cells to evade T cell-mediated immune response. ICIs have transformed the treatment landscape for various cancers due to their amazing efficacy. Many anti-tumor therapies, including targeted therapy, radiotherapy, and chemotherapy, combine ICIs to make the treatment more effective. However, the off-target immune activation caused by ICIs may lead to a broad spectrum of immune-related adverse events (irAEs) affecting multiple organ systems. Among irAEs, cardiotoxicity induced by ICIs, uncommon but fatal, has greatly offset survival benefits from ICIs, which is heartbreaking for both patients and clinicians. Consequently, such cardiotoxicity requires special vigilance, and it has become a common challenge both for patients and clinicians. This article reviewed the clinical manifestations and influence of cardiotoxicity from the view of patients and clinicians, elaborated on the underlying mechanisms in conjunction with animal studies, and then attempted to propose management strategies from a cardio-immuno-oncology multidisciplinary perspective.

Abstract We calculate the T T ¯ $$ T\overline{T} $$ -deformed entanglement entropy for integrable quantum field theories (IQFTs) using the form factor bootstrap approach. We solve the form factor bootstrap axioms for the branch-point twist fields and obtain the deformed form factors. Using these form factors, we compute the deformed von Neuman entropy up to two particle contributions. The solution of the form factor axioms is not unique. We find that for the simplest solution of the bootstrap axioms, the UV limit of the entanglement entropy takes the same form as the undeformed one, but the effective central charge is deformed. For solutions with additional CDD-like factors, we can have different behaviors. The IR corrections, which only depends on the particle spectrum is untouched.

Abstract Background This study aimed to investigate the value of nonenhanced computed tomography (CT)‐based radiomics in determining disease progression in breast cancer patients with bone marrow metastases and to develop a model for assessing treatment efficacy. Methods A total of 134 breast cancer patients with bone metastases were enrolled from three hospitals. Nonenhanced CT was performed after two cycles of drug treatment. The images were categorized into an invalid and a valid group according to disease progression status. The largest osteolytic lesions' maximum cross‐sections in the CT images were selected as regions of interest (ROIs) for feature extraction. Variance threshold, SelectKBest, and least absolute shrinkage and selection operator (LASSO) were used to reduce feature dimensionality. K‐nearest neighbor algorithm (KNN), support vector machine (SVM), extreme gradient boosting (XGBoost), random forest (RF), logistic regression (LR), and decision tree (DT) algorithms were trained to establish radiomics models. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic performance of the models. Results The KNN classifier demonstrated the best performance compared to the random grouping method. In the validation group, the area under the ROC curve (AUC) was 0.810. In the cross‐validation method, the RF classifier showed the best performance with an AUC of 0.84. Conclusion Nonenhanced CT‐based radiomics provides a promising method for evaluating the efficacy of systemic drug therapy in breast cancer patients with osteolytic bone metastases.

Abstract The Jiangmen Underground Neutrino Observatory is constructing the world’s largest liquid scintillator detector, with a 20 kt target mass and approximately 700 m of overburden. The total underground space of civil construction is around 300,000 m $$^3$$ 3 , with the main hall comprising about 120,000 m $$^3$$ 3 , making it the largest experimental hall in the world. Maintaining a low radon concentration in the underground air is crucial for both human health and the accuracy of experiments involving rare decay detection, such as neutrino and dark matter experiments. To ensure human health and the integrity of neutrino physics experiments, the nominal radon concentration in the main hall must be kept below 200 Bq/m $$^3$$ 3 with a maximum value below 400 Bq/m $$^3$$ 3 . Introduction of fresh air from above ground can significantly lower radon concentration. A benchmark experiment conducted in the refuge room near the main hall revealed that the radon emanating from underground water is a significant source of radon in the underground air. The total underground ventilation rate is approximately 160,000 m $$^3$$ 3 /h of fresh air with about 30 Bq/m $$^3$$ 3 $$^{222}$$ 222 Rn from the bottom of the vertical tunnel after the installation of powerful fans. Of this, 55,000 m $$^3$$ 3 /h is used for ventilation in the main hall. As a result of these measures, the radon concentration inside the main hall has decreased from 1600 Bq/m $$^3$$ 3 to below 200 Bq/m $$^3$$ 3 under stable working conditions, with exceptions during rare adverse weather events or fan failures. The employed strategies to control radon concentration in the underground air are described in this paper.

Power system flexibility is becoming increasingly critical in modern power systems due to the quick switch from fossil fuel-based power generation to renewables, old-fashioned infrastructures, and a sharp rise in demand. If a power system complies with financial restrictions and responds quickly to unforeseen shifts in supply and demand, it can be considered flexible. It can ramp up production during periods of high demand or increase it during unanticipated or scheduled events. The broad use of renewable energy in the power grid can provide environmental and economic benefits; nevertheless, renewables are highly stochastic in nature, with variability and uncertainty. New management with adequate planning and operation in the power system is necessary to address the challenges incorporated with the penetration of renewable energy. The primary aim of this review is to provide a comprehensive overview of power system flexibility, including appropriate definitions, parameters, requirements, resources, and future planning, in a compact way. Moreover, this paper potentially addresses the effects of various renewable penetrations on power system flexibility and how to overcome them. It also presents an emerging assessment and planning of influential flexibility solutions in modern power systems. This review’s scientific and engineering insights provide a clear vision of a smart, flexible power system with promised research direction and advancement.

The nonuniform distribution of fruit tree canopies in space poses a challenge for precision management. In recent years, with the development of Structure from Motion (SFM) technology, unmanned aerial vehicle (UAV) remote sensing has been widely used to measure canopy features in orchards to balance efficiency and accuracy. A pipeline of canopy volume measurement based on UAV remote sensing was developed, in which RGB and digital surface model (DSM) orthophotos were constructed from captured RGB images, and then the canopy was segmented using U-Net, OTSU, and RANSAC methods, and the volume was calculated. The accuracy of the segmentation and the canopy volume measurement were compared. The results show that the U-Net trained with RGB and DSM achieves the best accuracy in the segmentation task, with mean intersection of concatenation (MIoU) of 84.75% and mean pixel accuracy (MPA) of 92.58%. However, in the canopy volume estimation task, the U-Net trained with DSM only achieved the best accuracy with Root mean square error (RMSE) of 0.410 m3, relative root mean square error (rRMSE) of 6.40%, and mean absolute percentage error (MAPE) of 4.74%. The deep learning-based segmentation method achieved higher accuracy in both the segmentation task and the canopy volume measurement task. For canopy volumes up to 7.50 m3, OTSU and RANSAC achieve an RMSE of 0.521 m3 and 0.580 m3, respectively. Therefore, in the case of manually labeled datasets, the use of U-Net to segment the canopy region can achieve higher accuracy of canopy volume measurement. If it is difficult to cover the cost of data labeling, ground segmentation using partitioned OTSU can yield more accurate canopy volumes than RANSAC.

Abstract All‐solid‐state batteries (ASSBs) based on inorganic solid electrolytes fascinate a large body of researchers in terms of overcoming the inferior energy density and safety issues of existing lithium‐ion batteries. To date, the cathode designs in the ASSBs achieve remarkable achievements, adding the urgency of scaling up the battery system toward inorganic solid‐state pouch cell configuration for the application market. Herein, the recent developments of cathode materials and the design considerations for their application in the pouch cell format are reviewed to straighten out the roadmap of ASSBs. Specifically, the intercalation compounds and the conversion materials with conversion chemistries are highlighted and discussed as two potentially valuable material types. This review focuses on the basic electrochemical mechanisms, mechanical contact issues, and sheet‐type structure in inorganic solid‐state pouch cells with corresponding perspectives, thus guiding the future research direction. Finally, the benchmarks for manufacturing inorganic solid‐state pouch cells to meet practical high energy density targets are provided in this review for the development of commercially viable products.

This report outlines the case of a child affected by a type of congenital disorder of glycosylation (CDG) known as ALG2-CDG (OMIM 607906), presenting as a congenital myasthenic syndrome (CMS) caused by variants identified in ALG2, which encodes an α1,3-mannosyltransferase (EC 2.4.1.132) involved in the early steps of N-glycosylation. To date, fourteen cases of ALG2-CDG have been documented worldwide. From birth, the child experienced perinatal asphyxia, muscular weakness, feeding difficulties linked to an absence of the sucking reflex, congenital hip dislocation, and hypotonia. Over time, additional complications emerged, such as inspiratory stridor, gastroesophageal reflux, low intake, recurrent seizures, respiratory infections, an inability to maintain the head upright, and a global developmental delay. Whole genome sequencing (WGS) revealed the presence of two ALG2 variants in compound heterozygosity: a novel variant c.1055_1056delinsTGA p.(Ser352Leufs*3) and a variant of uncertain significance (VUS) c.964C>A p.(Pro322Thr). Additional studies, including determination of carbohydrate-deficient transferrin (CDT) revealed a mild type I CDG pattern and the presence of an abnormal transferrin glycoform containing a linear heptasaccharide consisting of one sialic acid, one galactose, one N-acetyl-glucosamine, two mannoses and two N-acetylglucosamines (NeuAc-Gal-GlcNAc-Man2-GlcNAc2), ALG2-CDG diagnostic biomarker, confirming the pathogenicity of these variants.

Abstract Background Tumor-associated inflammation suggests that anti-inflammatory medication could be beneficial in cancer therapy. Loratadine, an antihistamine, has demonstrated improved survival in certain cancers. However, the anticancer mechanisms of loratadine in lung cancer remain unclear. Objective This study investigates the anticancer mechanisms of loratadine in lung cancer. Methods A retrospective cohort of 4,522 lung cancer patients from 2006 to 2018 was analyzed to identify noncancer drug exposures associated with prognosis. Cellular experiments, animal models, and RNA-seq data analysis were employed to validate the findings and explore the antitumor effects of loratadine. Results This retrospective study revealed a positive association between loratadine administration and ameliorated survival outcomes in lung cancer patients, exhibiting dose dependency. Rigorous in vitro and in vivo assays demonstrated that apoptosis induction and epithelial-mesenchymal transition (EMT) reduction were stimulated by moderate loratadine concentrations, whereas pyroptosis was triggered by elevated dosages. Intriguingly, loratadine was found to augment PPARγ levels, which acted as a gasdermin D transcription promoter and caspase-8 activation enhancer. Consequently, loratadine might incite a sophisticated interplay between apoptosis and pyroptosis, facilitated by the pivotal role of caspase-8. Conclusion Loratadine use is linked to enhanced survival in lung cancer patients, potentially due to its role in modulating the interplay between apoptosis and pyroptosis via caspase-8.

The cavovarus foot is an acquired foot deformity with an incidence of about 1:100 000. It is caused by progressive forefoot pronation, resulting in a high-arched medial and mid-foot shape and a compensatory varus of the hindfoot (1) (Figs. 1 and 2). The aetiology of the cavovarus foot is complex to state. According to the current research, the main factor leading to a cavovarus foot is the imbalance of muscle strength, and the most common pathogenic factor is hereditary motor sensory neuropathy, found in 66% of children with high-arch malformation (2). Other factors include myelomeningocele, poliomyelitis, residual malformation of horseshoe feet, and post-traumatic cavovarus feet (3, 4). Cavovarus is not a single planar deformity but a three-dimensional planar deformity of the foot. Foot deformities are complex, requiring careful assessment of medical history, physical examination, and imaging analysis to fully evaluate children’s cavovarus deformity.

Abstract Background We investigated the synergistic effect of stress and habitual salt preference (SP) on blood pressure (BP) in the hospitalized Omicron-infected patients. Methods From 15,185 hospitalized Omicron-infected patients who reported having high BP or hypertension, we recruited 662 patients. All patients completed an electronic questionnaire on diet and stress, and were required to complete morning BP monitoring at least three times. Results The hypertensive group (n = 309) had higher habitual SP (P = 0.015) and COVID-19 related stress (P

Abstract Oxidative stress is the primary cause of ischaemic stroke and is closely related to circadian rhythm. However, the mechanism by which circadian rhythm regulates oxidative stress in ischaemic stroke remains elusive. The Silent Information Regulator 1 (SIRT1) controls circadian rhythm by activating the transcription of the circadian clock core protein Basic Helix-Loop-Helix ARNT Like 1 (BMAL1) through deacetylation. Studies have shown that the SIRT1-BMAL1 pathway can regulate oxidative stress. To investigate its correlation with oxidative stress, we examined the expression levels and influencing factors of SIRT1-BMAL1 at different times in ischaemic stroke patients and analyzed their clinical indexes, oxidative stress, and inflammatory factor indicators. The expression levels of oxidative stress and inflammatory factor indicators, including malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-α), SIRT1, and BMAL1, were detected in ischaemic stroke patients within 4.5 h of onset and in non-stroke patients. Patients were divided into four subgroups based on onset time: subgroup 1 (0:00–05:59); subgroup 2 (06:00–11:59); subgroup 3 (12:00–17: 59); and subgroup 4 (18:00–23:59). Our results showed higher MDA, IL-6, and TNF-α levels, and lower SOD, SIRT1, and BMAL1 levels in ischaemic stroke patients compared to control patients (P 0.05). Our findings suggest that the SIRT1-BMAL1 pathway may be involved in early oxidative stress in ischaemic stroke, which may be related to MPO.

The “3060” plan fully demonstrates the determination of China’s economic and social green and clean development. As an important secondary energy source, hydrogen has the advantages of high energy density, green and pollution-free, etc. As an ideal energy source in the future, green hydrogen is the final state of hydrogen energy prepared by electrical energy through electrolysis of water. The development of renewable energy hydrogen production will certainly help to achieve the goal of carbon peaking and carbon neutral. Therefore, the grid-connected control strategy of hydrogen production unit for weak grid is worthy of in-depth study. The research work in this paper is as follows: firstly, based on the analysis of the converter, a grid-connected control method of electric hydrogen production unit using virtual synchronization generator(VSG) control strategy is proposed. Secondly, a control method without phase-locked loop is adopted for the grid-connected phase synchronization part. Then, the stability of the proposed control strategy is demonstrated by using root locus plot. Finally, experimental verification is carried out. The experimental results show that the proposed control strategy makes the hydrogen production unit friendly to the weak grid with good adaptability, and at the same time, as a load, it can perform adaptive power regulation very well.

Abstract Background Thrombotic thrombocytopenic purpura (TTP) is a rare and fatal thrombotic microangiopathy-based hematologic disease. Stroke has been reported as atypical neurological manifestations of TTP in some cases. Case presentation A 65-year-old male presented with typical acute ischemic stroke symptoms including sudden-onset dysarthria, right-sided facial paralysis and hemiplegia. However, his CT and MRI scans were negative without showing any new ischemic lesions. He was diagnosed with TTP with severe thrombocytopenia, mild anemia, increased LDH, and low ADAMTS-13 activity. The symptoms and positive signs were rapidly resolved after administrating the plasma exchange therapy. Conclusion Clinicians should consider the possibility of TTP when a patient presents with acute stroke-like symptoms and thrombocytopenia, especially in an emergency room, either with or without new stroke lesions on the brain CT and MRI.

Abstract Background Th22 subset is a particular type of CD4+ T helper cells subset. Our study aimed to explore the expression level of circulating Th22, Th17, Th1, and Th2 cells and the possible mechanism of these cells in breast cancer (BC) with different pathological features. Methods Our study enrolled 43 newly diagnosed BC patients and 30 healthy controls. Frequencies of peripheral Th22, Th17, Th1, and Th2 cells were tested by flow cytometry. Concentrations of IL‐22 cytokine in plasma were examined by enzyme‐linked immunosorbent assay (ELISA). Real‐time PCR was done to test aromatic hydrocarbon receptor (AHR) and RAR‐associated orphan receptor C (RORC) gene expression. Results Frequencies of Th22, Th17, Th2 subsets, and the plasma IL‐22 level was obviously higher in the BC patients. A positive correlation between Th22 frequency and IL‐22 concentration in plasma was detected in BC patients. Furthermore, the percentage of Th22, Th2 subsets in peripheral blood of HER2 positive BC was higher than that in HER2 negative BC patients. A negative correlation between Th1 subset and Ki‐67% as well as a positive correlation between Th2 subset and Ki‐67% was found in BC patients. The proportion of Th1 cells in BC patients was significantly lower than that of the control group. Expression of AHR and RORC transcription factors were also observed to be upregulated in the BC patients. Furthermore, Th22 cells were positively correlated with BC tumor stage and clinical outcomes. The BC patients with a higher percentage of Th22, Th17, Th1 cells or a lower percentage of Th1 cells showed a decreased trend of survival rate. Conclusion Th22, Th17, Th1, and Th2 subsets may play an essential role in BC patients. Th22, Th17, Th1, and Th2 cells may have potential significance to be used as clinical markers in BC patients with different molecular classification. Th22 cells may have potential value in BC patients’ outcomes prediction, providing clinical value.