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Abstract This study investigates the effectiveness of a Low-Cost Single-Channel BCI system in improving mathematical learning outcomes, self-efficacy, and alpha power in university students. Eighty participants were randomly assigned to either a BCI group receiving real-time neurofeedback based on alpha rhythms or a sham feedback group. Results showed that the BCI group had significantly higher mathematical performance, self-efficacy, and alpha power compared to the sham feedback group. Mathematics performance, alpha wave intensity, and self-efficacy showed significant positive correlations after training, indicating that neurofeedback training may have promoted their interaction and integration. These findings demonstrate the potential of BCI technology in enhancing mathematical learning outcomes and highlight the importance of considering pre-test performance and self-efficacy in predicting learning outcomes, with implications for personalized learning interventions and the integration of BCI technology in educational settings.

Abstract The fundamental leucine zipper (bZIP) genes play a crucial role as transcriptional coactivators in plants. Pseudoroegneria libanotica served as the maternal contributor to several species within the tribe Triticeae (Poaceae), exhibiting commendable resilience to various stressors. Consequently, bZIP genes of Pseudoroegneria libanotica response to abiotic stresses was important for further understanding of stress tolerance studies in Triticeae. A total of 108 PsebZIPs were identified in this study, and they were divided into 10 subgroups. PsebZIPs were found to be extensively involved in the biological activities within P. libanotica. The RNA-seq results revealed differential responses of PsebZIPs to drought stress in both aerial and root tissues. PsebZIP44 and PsebZIP46 were regarded as potential genes capable of responding to abiotic stress, and their varying degrees of responsiveness to drought, salinity, heavy metals, heat, and oxidative stress have been demonstrated in yeast. Homologous proteins with intact bZIP gene structures of PsebZIP44 or PsebZIP46 have not been identified in wheat. The current investigation not only provides a fundamental basis for further probing into the biological functions of PsebZIPs within P. libanotica but also reveals previously undiscovered potential genes with the ability to respond to abiotic stress. They could contribute to improving the genetic constitution of Triticeae crops, including wheat.

Abstract Certain immune-checkpoint inhibitors have a narrow therapeutic window (TW) as cancer therapeutics, and engineered dual-/multi-targeting agents could potentially widen the TW to bring true clinical benefits. We report a new rationally-designed bispecific-antibody (BsAb), HX009, simultaneously targeting PD1 and CD47 to improve both the efficacy and safety over the respective single-targeting agents by grafting the extracellular domain of SIRPα onto the parental anti-PD1-monoclonal antibody, HX008. This resulted in an IgG4-based “2 × 2” symmetric structure but with an intentionally-reduced CD47-binding affinity, suggesting a novel candidate cancer immunotherapy. Specifically, HX009 has binding affinity constant of 8.951 × 10–9 M for human PD1 and 2.557 × 10–8 M for human CD47, respectively, where the CD47 binding is significantly weaker as compared to the binding affinity of HX008 to PD1 as well as the binding affinity of SIRPα-Fc to CD47, leading to little binding to RBCs and platelets and is contrasting to many CD47-agents in development. However, HX009 effectively and simultaneously binds to the PD1 and CD47 on PD1+CD47+ T-cells via cis-binding and elicits enhanced T cell activation compared to the parental HX008. HX009 caused little cytokine-release in human peripheral blood mononuclear cells. HX009 cross-species binds to cynomolgus monkey PD1/CD47 but not to rodents, making cynomolgus monkeys the choice of species to investigate the pharmacokinetics (PK) and toxicology of HX009. HX009’s anti-tumor activities were confirmed in several humanized preclinical mouse models by determining either its anti-PD1 (humanized hu-CD47-MC38 models) or anti-CD47 (HuT-102 lymphoma CDX and three PDX-AML models) functions, although limited available humanized models have hindered broadly demonstration of enhanced anti-tumor activities contributed from the dual targeting of the BsAb. The expanded DLBCL-PDX trial data suggested that both EBV-status and OX40 expression could potentially be two positive predictors for response to HX009. An intravenous (IV) infusion PK study in cynomolgus monkey revealed its largely vasculature distribution, terminal half-life (T1/2) of ~ 50 h, and dose-proportional exposure without accumulation. The anti-drug antibody (ADA) was observed in all monkeys as expected, affecting the PK parameters of repeated administration. The IV single-dose toxicology study with a 14-day observation revealed a maximum tolerated dose of 150 mg/kg, while the repeated-dose (once weekly for 4 weeks, 5 doses in total) study showed a highest non-severely toxic dose (HNSTD) of 15 mg/kg. The desired preclinical PK and safety profiles, along with its antitumor activity, support HX009’s candidacy for its clinical development.

Abstract Background Crop rotation is a sophisticated agricultural practice that can modify the demographic structure and abundance of microorganisms in the soil, stimulate the growth and proliferation of beneficial microorganisms, and inhibit the development of harmful microorganisms. The stability of the rhizosphere microbiome is crucial for maintaining both soil ecosystem vitality and crop prosperity. However, the effects of extended garlic‒maize rotation on the physicochemical characteristics of garlic rhizosphere soil and the stability of its microbiome remain unclear. To investigate this phenomenon, soil samples from the garlic rhizosphere were collected across four different lengths of rotation in a garlic–maize rotation. Results There were notable positive associations between the total nitrogen and total phosphorus contents in the soil and the duration of rotation. Prolonged rotation could increase the maintenance of microbiome α diversity. The number of years of rotation and the soil organic carbon (SOC) content emerged as principal determinants impacting the evolution of the bacterial community structure, with the SOC content playing a pivotal role in sculpting the species diversity within the garlic rhizosphere bacterial community. Additionally, SOC remains predominant in shaping the root-associated bacterial community’s β-nearest taxon index. However, these factors do not have a notable effect on the fungal community inhabiting the garlic rhizosphere. In comparison with monoculture, rotation can amplify the interconnectivity and intricacy of microbial ecological networks. Long-term rotation can further maintain the stability of both microbial ecological networks and interactions between bacterial and fungal communities. It can enlist a plethora of beneficial Bacillus species microorganisms within the garlic rhizosphere to form a biological barricade that aids in safeguarding garlic against encroachment by the pathogenic fungus Fusarium oxysporum, consequently diminishing disease incidence. This study provides a theoretical foundation for the sustainable development of garlic through long-term crop rotation with maize. Conclusions Our research results indicate that long-term garlic‒maize rotation maintains stable garlic rhizosphere microecology. Our study provides compelling evidence for the role of long-term crop rotation in maintaining microbiota and community stability, emphasizing the importance of cultivating specific beneficial microorganisms to enhance rotation strategies for garlic farming, thereby promoting sustainability in agriculture.

Abstract Background Abnormal sensory perception, particularly pain insensitivity (PAI), is a typical symptom of autism spectrum disorder (ASD). Despite the role of myelin metabolism in the regulation of pain perception, the mechanisms underlying ASD-related PAI remain unclear. Methods The pain-associated gene sphingosine-1-phosphate receptor 1 (S1PR1) was identified in ASD samples through bioinformatics analysis. Its expression in the dorsal root ganglion (DRG) tissues of BTBR ASD model mice was validated using RNA-seq, western blot, RT-qPCR, and immunofluorescence. Pain thresholds were assessed using the von Frey and Hargreaves tests. Patch-clamp techniques measured KCNQ/M channel activity and neuronal action potentials. The expression of S1PR1, KCNQ/M, mitogen-activated protein kinase (MAPK), and cyclic AMP/protein kinase A (cAMP/PKA) signaling proteins was analyzed before and after inhibiting the S1P-S1PR1-KCNQ/M pathway via western blot and RT-qPCR. Results Through integrated transcriptomic analysis of ASD samples, we identified the upregulated gene S1PR1, which is associated with sphingolipid metabolism and linked to pain perception, and confirmed its role in the BTBR mouse model of ASD. This mechanism involves the regulation of KCNQ/M channels in DRG neurons. The enhanced activity of KCNQ/M channels and the decreased action potentials in small and medium DRG neurons were correlated with PAI in a BTBR mouse model of ASD. Inhibition of the S1P/S1PR1 pathway rescued baseline insensitivity to pain by suppressing KCNQ/M channels in DRG neurons, mediated through the MAPK and cAMP/PKA pathways. Investigating the modulation and underlying mechanisms of the non-opioid pathway involving S1PR1 will provide new insights into clinical targeted interventions for PAI in ASD. Conclusions S1PR1 may contribute to PAI in the PNS in ASD. The mechanism involves KCNQ/M channels and the MAPK and cAMP/PKA signaling pathways. Targeting S1PR1 in the PNS could offer novel therapeutic strategies for the intervention of pain dysesthesias in individuals with ASD.

The increasing frequency of cervical and lumbar spine disorders, driven by aging and evolving lifestyles, has led to a rise in spinal surgeries using pedicle screws. Robotic spinal surgery systems have emerged as a promising innovation, offering enhanced accuracy in screw placement and improved surgical outcomes. We focused on literature of this field from the past 5 years, and a comprehensive literature search was performed using PubMed and Google Scholar. Robotic spinal surgery systems have significantly impacted spinal procedures by improving pedicle screw placement accuracy and supporting various techniques. These systems facilitate personalized, minimally invasive, and low‐radiation interventions, leading to greater precision, reduced patient risk, and decreased radiation exposure. Despite advantages, challenges such as high costs and a steep learning curve remain. Ongoing advancements are expected to further enhance these systems' role in spinal surgery.

Abstract The oral and maxillofacial region comprises a variety of organs made up of multiple soft and hard tissue, which are anatomically vulnerable to the pathogenic factors of trauma, inflammation, and cancer. The studies of this intricate entity have been long-termly challenged by a lack of versatile preclinical models. Recently, the advancements in the organoid industry have provided novel strategies to break through this dilemma. Here, we summarize the existing biological and engineering approaches that were employed to generate oral and maxillofacial organoids. Then, we detail the use of modified co-culture methods, such as cell cluster co-inoculation and air-liquid interface culture technology to reconstitute the vascular network and immune microenvironment in assembled organoids. We further retrospect the existing oral and maxillofacial assembled organoids and their potential to recapitulate the homeostasis in parental tissues such as tooth, salivary gland, and mucosa. Finally, we discuss how the next-generation organoids may benefit to regenerative and precision medicine for treatment of oral-maxillofacial illness.

The single-phase face-centered cubic medium-entropy alloys (MEAs) normally have coarse grains in as-cast state, which exhibit insufficient strength for engineering applications. Here, a superior tensile strength-ductility synergy in a fine grained (CoCrNi)94Al3Ti3 MEA hardened by nanoscale L12 precipitates was fabricated by spark plasma sintering (SPS) and post-sintering in-situ precipitation treatment. The SPSed MEAs have a fine grain size of ⁓ 5 μm, and a high number density of L12 precipitates form after in-situ annealing within the SPS machine. A high tensile yield strength of 1141 MPa with an adequate elongation to fracture of 25.8% was achieved in (CoCrNi)94Al3Ti3 MEA after annealing at 700 °C for 4 h. Electron backscattered diffraction and transmission electron microscopy characterizations indicate that the superior mechanical properties mainly originate from fine grains and the coherent spherical L12 precipitates. The dislocation slips and stacking faults prevail in all SPSed MEAs during tensile deformation, while extra Lomer-Cottrell locks are observed in annealed MEAs. The deformation twinning is absent in these precipitation-hardened MEAs with a low stacking fault energy, which may be attributed to the fine grains and numerous nanoscale L12 precipitates. This study not only confirms the effectiveness of powder metallurgy when sintering and precipitation are combined in-situ during the SPS cycle, but also provide guidance for the microstructure regulation process and practical applications of SPSed HEAs/MEAs.

Abstract Lung adenocarcinoma (LUAD) is the most common lung cancer, accounting for 19.4% of all cancer deaths. Our previous study discovered that INTS7 expression was upregulated in LUAD, while the precise mechanism by which INTS7 exerts pro-cancer effects remains unknown. In our study, shRNA was used to knockdown the expression of INTS7 in A549 cells. Cancer behaviors in vitro were determined by CCK8 and transwell assays. Xenograft mice models were constructed to detect the tumorigenesis in vivo. Immunofluorescence and toluidine blue staining were used to test the immune infiltration. Bioinformatics analysis was adopted to predict the potential signaling pathways and construct INTS7-derived genomic prognostic model. Western blot was utilized to confirm the molecular pathways. In total, downregulation of INTS7 suppressed proliferation, invasion and migration of A549 cells, as well as tumor growth. Bioinformatics and western blot analysis indicated that p38MAPK pathway participated in the regulatory mechanism of INTS7. Moreover, INTS7 expression was negatively correlated with infiltration of memory B cells and mast cells, while positively correlated with infiltration of macrophages M2. A nomogram, including INTS7-derived risk score, was used to estimate individual’s survival probability. Generally, our findings provided comprehensive understanding of the molecular mechanisms about INTS7, and targeting INTS7 may represent a potential therapy for LUAD.

Abstract Purpose This study aimed to investigate the real-world use and clinical outcomes of tixagevimab/cilgavimab in China during the Omicron outbreak in late 2022. Methods This observational, real-world study included patients who received tixagevimab/cilgavimab from July 9 to December 30, 2022, in Hainan, China. Here, we report the baseline and characteristics and interim analysis results of the clinical outcomes in those receiving at least one dose of tixagevimab/cilgavimab (300 mg) for pre-exposure prophylaxis. Results Among 248 subjects who received tixagevimab/cilgavimab, 229 subjects were included in this analysis. Until March 28, 2023, the median follow-up was 95 days. The mean age of the subjects was 44.4 ± 15.9 years, 11.8% were ≥ 65 years, and 41.5% were male. Fifty-eight (25.3%) subjects had comorbidities, 16.2% subjects had key immune compromised conditions. Seventy-two (32.6%) patients had laboratory-confirmed SARS-CoV-2 infection and/or received healthcare within three months; 71/72 (98.6%) had mild disease, and one (1.4%) was moderate. No COVID-19-related intensive care unit (ICU) admissions, extracorporeal membrane oxygenation utilizations, or death occurred. Two (0.9%) patients required hospitalization. One (0.4%) serious adverse event occurred, which was considered unrelated to tixagevimab/cilgavimab. Conclusion Among Chinese patients receiving prophylactic tixagevimab/cilgavimab, the incidence of COVID-19-related hospitalization, ICU admission, or death was low during the Omicron surge. Further randomized controlled trials with larger sample sizes are needed to determine the effectiveness of tixagevimab/cilgavimab in preventing severe COVID-19 outcomes. Trial registration The study was registered with clinicaltrial.gov (NCT05917951).

Abstract Objective Knee osteoarthritis (KOA) is usually bilateral. In many patients, the degree of bilateral knee degeneration varies, with one side involving multiple compartments and the other a single compartment degeneration. Therefore, the objective of this study was to compare the early clinical efficacy of simultaneous bilateral and staged total knee arthroplasty (TKA) combined with unicompartmental knee arthroplasty (UKA) in the treatment of bilateral KOA with different degrees. Methods We compared clinical data from 71 simultaneous bilateral TKA/UKA (SB-TKA/UKA) patients with 52 Staged TKA/UKA (Staged-TKA/UKA) patients. Staged-TKA/UKA is defined as TKA on one knee followed by UKA on the other knee. The comparison included Hospital for Special Surgery (HSS) score, range of motion(ROM), complication rate and prosthetic survival rate at the last follow-up between the two groups. Results The follow-up time of SB-TKA/UKA group was (69.08 ± 14.35) months, and that of Staged-TKA/UKA group was (73.25 ± 18.39) months. Staged-KA/UKA group had a shorter hospital stays, less hospitalization costs and shorter operating time (p 0.05). There was no significant difference in complication rate between the two groups (χ2 = 0.56, p = 0.454). For the TKA-side knee joint, there was no significant difference in the prosthetic survival rate (χ2 = 0.05, p = 0.824) and the prosthetic survival curve (χ2 = 0.052, p = 0.82) between the two groups. For UKA-side knee joint, there was no significant difference in prosthetic survival rate (χ2 = 0.08, p = 0.777) and prosthetic survival curve (χ2 = 0.074, p = 0.786) between the two groups. Conclusions Compared to Staged-TKA/UKA, SB-TKA/UKA has the same early clinical efficacy, shorter operating time and hospital stays, less hospitalization costs, and no increased postoperative complications and prosthesis revision rates. Therefore, SB-TKA/UKA may be recommended for patients who can tolerate simultaneous bilateral surgery as assessed before surgery.

Abstract The NLR family pyrin domain containing 3 (NLRP3) inflammasome in microglia is intimately linked to the pathogenesis of Alzheimer’s disease (AD). Although NLRP3 inflammasome activity is regulated by cellular metabolism, the underlying mechanism remains elusive. Here, we found that under the pathological conditions of AD, the activation of NLRP3 inflammasome in microglia is accompanied by increased glutamine metabolism. Suppression of glutaminase, the rate limiting enzyme in glutamine metabolism, attenuated the NLRP3 inflammasome activation both in the microglia of AD mice and cultured inflammatory microglia. Mechanistically, inhibiting glutaminase blocked the anaplerotic flux of glutamine to the tricarboxylic acid cycle and amino acid synthesis, down-regulated mTORC1 signaling by phosphorylating AMPK, which stimulated mitophagy and limited the accumulation of intracellular reactive oxygen species, ultimately prevented the activation of NLRP3 inflammasomes in activated microglia during AD. Taken together, our findings suggest that glutamine metabolism regulates the activation of NLRP3 inflammasome through mitophagy in microglia, thus providing a potential therapeutic target for AD treatment.

Objective: Perihematomal edema (PHE) is one of the significant secondary cerebral damages, with the blood–brain barrier's integrity playing a pivotal role in its progression. Strengthening tight junction (TJ) proteins enhances blood–brain barrier integrity, yet the complex genetics behind brain edema remain not fully understood. Our research endeavors to uncover pivotal genes and their roles in brain edema following cerebral hemorrhage, and to investigate potential treatment strategies. Methods: By analyzing intracerebral hemorrhage (ICH) and control samples using the GSE216607 and GSE206971 datasets, we identified differentially expressed genes. Cross-referencing with the KEGG database, we aligned these genes with those related to tight junctions. Extensive enrichment analysis and protein interactions were performed to examine the expression and clinical significance of the identified genes. Our study employed the C57BL/6J mouse ICH model and qRT-PCR for key gene validation. Results: Notably, VASP, HCLS1, MSN, and EZR, critical for tight junctions, showed increased expression post-ICH, emphasizing their significance in BBB upkeep and PHE progression. Drug validation indicated potential therapeutic effects of Testosterone enanthate, SELENIUM, and LY 294002 on tight junction-related genes. Conclusion: This study sheds light on the potential involvement of these genes in brain edema progression post-ICH, offering promising therapeutic targets. Further research is needed for deeper understanding.

Abstract Evidences regarding the feasibility of transcatheter arterial chemoembolization (TACE)-based therapy for unresectable hepatocellular carcinoma (uHCC) remains limited. This study aimed to investigate the efficacy and safety of TACE combined with envafolimab and lenvatinib for uHCC. Eligible patients with uHCC received envafolimab and lenvatinib after TACE until disease progression, conversion to surgery, intolerable toxicities, or death. The primary endpoint was the objective response rate (ORR) assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Between March 2022 and July 2022, 38 patients were included for safety analysis, and 36 patients were included for efficacy analysis. As of the data cutoff (13 December 2023), the median follow-up was 16.9 months. The ORR was 50%, and disease control rate (DCR) was 83.3% per RECIST 1.1 (ORR and DCR of both 83.3% per modified RECIST (mRECIST)). The median progression-free survival (PFS) was 7.58 months. Of 36 patients, 17 patients were converted to resectable HCC with a surgical conversion rate of 47.2%, and 16 patients underwent surgery with R0 resection rate of 100%, pathologic complete response (pCR) rate of 31.3%. Overall incidences of treatment-related adverse events (TRAEs) of any grade was 97.4%. Grade ≥ 3 TRAEs were observed in 52.6% patients. No treatment-related deaths occurred. Image mass cytometry (IMC) analysis revealed that combined treatment improved the immune status of the tumor microenvironment, and resident macrophages had the potential to predict efficacy of this treatment. Envafolimab plus lenvatinib and TACE yielded promising survival outcomes and conversion efficiency with a tolerable safety profile. Trial registration Clinical trials: NCT05213221.

Abstract We elaborate on a new recursive method proposed in [1] for computing tree-level n-point supergluon amplitudes as well as those with one gluon, i.e. spinning amplitudes, in AdS5 × S 3. We present an improved proof for the so-called “constructibility” of supergluon and spinning amplitudes based on their factorizations and flat-space limit, which allows us to determine these amplitudes in Mellin space to all n. We present explicit and remarkably simple expressions for up to n = 7 supergluon amplitudes and n = 6 spinning amplitudes, which can be viewed as AdS generalizations of the scalar-scaffolded gluon amplitudes proposed recently. We then reveal a series of hidden structures of these AdS amplitudes including (1). an understanding of general pole structures especially the precise truncation on descendent poles (2). a derivation of simple “Feynman rules” for the all-n amplitudes with the simplest R-symmetry structures, and (3). certain universal behavior analogous to the soft/collinear limit of flat-space amplitudes.

Abstract Epilepsy is one of the most common symptoms in patients with gliomas; however, the mechanisms underlying its interaction are not yet clear. Moreover, epidemiological studies have not accurately identified patients with glioma-related epilepsy (GRE), and there is an urgent need to identify the molecular mechanisms and markers of its occurrence. We analyzed the demographics, transcriptome, whole-genome, and methylation sequences of 997 patients with glioma, to determine the genetic differences between glioma and GRE patients and to determine the upregulated molecular function, cellular composition, biological processes involved, signaling pathways, and immune cell infiltration. Twelve machine learning algorithms were refined into 113 combinatorial algorithms for building diagnostic recognition models. A total of 342 patients with GRE were identified with WHO grade 2 (174), grade 3 (107), and grade 4 (61). The mean age of the patients with GREs, with IDH mutations (n = 217 [63%]) and 1p19q non-codeletion (n = 169 [49%]), was 38 years old. GRE molecular functions were mainly passive transmembrane transporter protein activity, ion channel activity, and gated channel activity. Cellular components were enriched in the cation-channel and transmembrane transporter complexes. Cerebral cortical development regulates the membrane potential and synaptic organization as major biological processes. The signaling pathways mainly focused on cholinergic, GABAergic, and glutamatergic synapses. LASSO, combined with Random Forest, was the best diagnostic model and identified nine diagnostic genes. This study provides new insights and future perspectives for resolving the molecular mechanisms of GRE.

Seed size is an important agronomic trait in melons that directly affects seed germination and subsequent seedling growth. However, the genetic mechanism underlying seed size in melon remains unclear. In the present study, we employed Bulked-Segregant Analysis sequencing (BSA-seq) to identify a candidate region (~1.35 Mb) on chromosome 6 that corresponds to seed size. This interval was confirmed by QTL mapping of three seed size-related traits from an F2 population across three environments. This mapping region represented nine QTLs that shared an overlapping region on chromosome 6, collectively referred to as qSS6.1. New InDel markers were developed in the qSS6.1 region, narrowing it down to a 68.35 kb interval that contains eight annotated genes. Sequence variation analysis of the eight genes identified a SNP with a C to T transition mutation in the promoter region of MELO3C014002, a leucine-rich repeat receptor-like kinase (LRR-RLK) gene. This mutation affected the promoter activity of the MELO3C014002 gene and was successfully used to differentiate the large-seeded accessions (C-allele) from the small-seeded accessions (T-allele). qRT-PCR revealed differential expression of MELO3C014002 between the two parental lines. Its predicted protein has typical LRR-RLK family domains, and phylogenetic analyses reveled its similarity with the homologs in several plant species. Altogether, these findings suggest MELO3C014002 as the most likely candidate gene involved in melon seed size regulation. Our results will be helpful for better understanding the genetic mechanism regulating seed size in melons and for genetically improving this important trait through molecular breeding pathways.

Background: To evaluate the effectiveness and safety of the Shenfu injection (SFI) combined with standard bundle treatment in septic patients with hypoperfusion. Method: This study was a multi-center, randomized, open-label, controlled trial conducted in four teaching hospitals in China. The septic patients with hypoperfusion and traditional Chinese medicine (TCM) syndrome with Yang-Qi deficiency were enrolled from January 2019, through September 2020. Eligible patients were randomly allocated in a 1:1 ratio to either receive 60 mL of SFI infusion per day plus standard treatment (SFI group) or standard bundle treatment alone (control group). The primary outcome was 28-day all-cause mortality. Secondary outcomes were 90-day all-cause mortality time to weaning from mechanical ventilation, time to weaning from vasopressors, time to discharge from the ICU and hospital, and laboratory results after randomization. Results: A total of 188 patients completed the trail. This study revealed that the results of the SFI group and the control groups were not statistically significant in 28-day all-cause mortality (10.6% vs. 20.2%, respectively; P=0.106). The infusion of SFI was associated with a significant reduction in the duration of vasopressor use (median=4.0 days, interquartile range [IQR]: 2.0 days–6.0 days vs. median=5.0 days, IQR: 3.0 days–8.0 days, respectively; P=0.043). Patients in the SFI group had statistically greater reductions in plasma lactate levels compared with those in the control group at the first 12 h (median=1.1 mmol/L, IQR: 0.3–2.0 mmol/L vs. median=0.0 mmol/L, IQR: −0.2 to 0.8 mmol/L, respectively; P

Hurricane Ian in 2022 was a destructive category 4 Atlantic hurricane striking the state of Florida, which caused hundreds of deaths and injuries, catastrophic property damage, and an economic loss of more than $112 billion. Before the landfall of Ian in Florida, the state government issued evacuation orders in high-risk zones to reduce casualties and injuries. However, there is limited data available to monitor the actual evacuation patterns and compliance with the evacuation orders at a large geographic scale. This study utilizes human mobility data (i.e. SafeGraph Weekly Pattern) to analyse the spatial patterns of evacuation during Hurricane Ian in 2022. The objectives of the study include three key aspects: 1) proposing an analytical workflow that utilizes human mobility data to detect mobility patterns in disasters and other emergency events; 2) identifying significant evacuation patterns, and 3) revealing the spatial variations in the compliance with evacuation orders in the affected areas. Using data science and spatial analysis techniques, this study detected notable changes in population movements, both within Florida and nationwide, which are potentially linked to the hurricane-induced population evacuation. The distance decay pattern of population flows from Florida demonstrates a propensity for individuals to relocate to nearby areas during the hurricane. Furthermore, the increase in population outflows from the impacted areas suggests the effectiveness of mandatory evacuation orders. A more pronounced increase in outflows from designated mandatory evacuation areas points to the public awareness of the evacuation zone designation. This study provides large-scale, fine-resolution analysis of evacuation behaviours in natural disasters which cannot be easily detected in traditional data sources. The analytical workflows provide actionable tools for government agencies and policymakers to evaluate the effectiveness of evacuation orders and improve evacuation plans in future disasters.

Abstract Background The Bucephalidae is a large family of digenean trematodes but most previous analyses of its phylogenetic position have relied on a single mitochondrial gene or morphological features. Mitochondrial genomes (mitogenomes) remain unavailable for the entire family. To address this, we sequenced the complete mitogenome of Dollfustrema vaneyi and analyzed the phylogenetic relationships with other trematodes. Results The circular genome of Dollfustrema vaneyi spanned 14,959 bp and contained 12 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and a major non-coding region. We used concatenated amino acid and nucleotide sequences of all 36 genes for phylogenetic analyses, conducted using MrBayes, IQ-TREE and PhyloBayes. We identified pronounced topological instability across different analyses. The addition of recently sequenced two mitogenomes for the Aspidogastrea subclass along with the use of a site-heterogeneous model stabilized the topology, particularly the positions of Azygiidae and Bucephalidae. The stabilized results indicated that Azygiidae was the closest lineage to Bucephalidae in the available dataset, and together, they clustered at the base of the Plagiorchiida. Conclusions Our study provides the first comprehensive description and annotation of the mitochondrial genome for the Bucephalidae family. The results indicate a close phylogenetic relationship between Azygiidae and Bucephalidae, and reveal their basal placement within the order Plagiorchiida. Furthermore, the inclusion of Aspidogastrea mitogenomes and the site-heterogeneous model significantly improved the topological stability. These data will provide key molecular resources for future taxonomic and phylogenetic studies of the family Bucephalidae.

Abstract Fe1-x O, although chemically simple, possesses a complex structural and magnetic phase diagram. The crystal structures of Fe1-x O and its magnetic properties at extreme conditions are still a matter of debate. Here, we performed a systematic investigation on Fe0.94O up to 94 GPa and 1700 K using synchrotron X-ray diffraction and synchrotron Mössbauer source spectroscopy. We observe a transition of Fe0.94O to the monoclinic phases above 40 GPa and at high temperatures and use the group theory analysis of the observed phases to discuss their properties and their relation to the ambient pressure phases. The Mössbauer spectra of the rhombohedral and the room temperature monoclinic phase contain a component attributed to Fe2.5+, caused by the electron exchange between the Fe3+ defect and neighboring Fe2+ atoms. Our results present a structural and magnetic transitional pressure-temperature diagram of Fe1-x O and show the complex physicochemical properties of simple Fe1-x O binary oxide under extreme conditions.

Abstract The main cause of gastric cancer (GC)-related death is due to malignant cell unregulated distant metastasis and proliferation. Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) has been shown to play an important role in carcinogenesis and the development of metastasis in several tumors. However, its downstream regulatory mechanism in GC is not well defined. Our study aims to investigate the function and regulatory mechanism of hnRNPA1 in GC. We analyzed the differential expression of hnRNPA1 in gastric cancer and paired adjacent normal tissues in the TCGA database. Kaplan-Meier analysis was employed for survival assessment. The expressions of hnRNPA1 in GC cells were measured by qRT-PCR and Western blot. Transwell assay, CCK8 and colony formation assay were used to detect the effect of hnRNPA1 on the metastasis and proliferation ability of GC cells. Additionally, Western blotting was performed to examine the expression of proteins related to the Wnt/β-catenin signaling pathway as well as epithelial-mesenchymal transition (EMT), while further investigations were carried out to explore potential regulatory mechanisms. The results showed that hnRNPA1 was highly expressed differentially in GC over normal gastric tissue. Knocking down hnRNPA1 inhibited the metastasis and proliferation of human gastric cancer cells. Overexpression of hnRNPA1 significantly enhanced the metastatic potential and proliferative capacity of human GC cells. Further mechanism exploration revealed that knocking down hnRNPA1 inhibited the Wnt/β-catenin signaling pathway and WNT1 inducible signaling pathway protein-2 (WISP2), an activator of the Wnt/β-catenin signaling pathway. Whereas overexpression of hnRNPA1 had the opposite effects. Our results demonstrated that hnRNPA1 promoted metastasis and proliferation of GC cells by activating Wnt/β-catenin signaling pathway via WISP2. hnRNPA1 may serve as a potential biomarker and novel therapeutic targets for GC.

Abstract The development of hydrogen technologies is at the heart of a green economy. As prerequisite for implementation of hydrogen storage, active and stable catalysts for (de)hydrogenation reactions are needed. So far, the use of precious metals associated with expensive costs dominates in this area. Herein, we present a new class of lower-cost Co-based catalysts (Co-SAs/NPs@NC) in which highly distributed single-metal sites are synergistically combined with small defined nanoparticles allowing efficient formic acid dehydrogenation. The optimal material with atomically dispersed CoN2C2 units and encapsulated 7-8 nm nanoparticles achieves an excellent gas yield of 1403.8 mL·g−1·h−1 using propylene carbonate as solvent, with no activity loss after 5 cycles, which is 15 times higher than that of the commercial Pd/C. In situ analytic experiments show that Co-SAs/NPs@NC enhances the adsorption and activation of the key intermediate monodentate HCOO*, thereby facilitating the following C-H bond breaking, compared to related single metal atom and nanoparticle catalysts. Theoretical calculations show that the integration of cobalt nanoparticles elevates the d-band center of the Co single atoms as the active center, which consequently enhances the coupling of the carbonyl O of the HCOO* intermediate to the Co centers, thereby lowering the energy barrier.

Abstract Background Obesity is accompanied by inflammation, which significantly affects the homeostasis of the immune microenvironment. Hematopoietic stem cells (HSCs), residing primarily in the bone marrow, play a vital role in maintaining and producing diverse mature blood cell lineages for the adult hematopoietic and immune systems. However, how HSCs development is affected by obese-promoting inflammation, and the mechanism by which HSC hematopoietic potency is affected by inflammatory signals originating from the obese-promoting changes on bone marrow niche remain unclear. This study elucidates the relationship between obesity-promoting inflammation and HSC fate determination. Methods The obesity mice model was established by feeding C57BL/6J mice a high-fat diet (HFD) containing 60% kcal fat. After 6 weeks, HSCs were analyzed using flow cytometry and identified key inflammation cytokine. Transcriptome sequencing techniques were used to discern the distinct pathways in HSCs. Ultimately, confirming the biological mechanism of obesity-induced HSC fate changes via Anakinra blocking specific inflammatory signals. Results Obesity caused by HFD changed the physical and biochemical properties of the bone marrow niche. In the HFD mice, the population of long-term HSCs in the bone marrow was decreased and facilitated HSCs differentiation towards the myeloid lineage. In addition, HFD increased expression of the inflammatory factor IL-1β in the bone marrow, and a significantly increased expression of IL-1r1 and active p38/MAPK signaling pathway were detected in the HSCs. Inhibition of IL-1β further normalized the expression of genes in p38/MAPK pathway and reversed HSC fate. Conclusions These findings have been demonstrated that the p38/MAPK signaling pathway in HSCs is activated by elevated levels of IL-1β within the HSC niche in obese models, thereby regulating HSC differentiation. It suggested a direct link between obesity-promoting inflammation and myeloid differentiation bias of HSCs in the HFD mice. Graphical abstract

The enhanced coalbed methane (ECBM) technology has the potential to enhance coal seam gas extraction efficiency, while also achieving CO2 storage, thereby promoting the dual carbon reduction goals. It holds broad prospects for its application in unconventional natural gas development. The fracture structure and distribution within coal seams determine the effectiveness of supercritical carbon dioxide (SC-CO2) fracturing, which is pivotal in enhancing coal seam gas extraction efficiency. Under prolonged exposure, the adsorption swelling and dissolution-extraction effects generated by SC-CO2 interacting with coal can alter the morphology of coal fractures. However, during the fracturing process, the contact time between SC-CO2 and coal is relatively short, thus the impact of the adsorption swelling and dissolution-extraction effects of supercritical carbon dioxide on coal fractures under short-term conditions remains unclear. Therefore, this study investigated the evolution of coal fractures under a short-term SC-CO2 exposure. Different metamorphic coal samples were studied through CT scans to observe the variations in fractures with accumulated immersion time. A grayscale distribution function of CT two-dimensional scan images was established, and the relationship between immersion time and fracture evolution patterns was constructed. This was combined with the XRD experiments to examine the impact of immersion time on the changes in coal composition. The primary factors driving the evolution of coal fractures under a short-term SC-CO2 exposure were thus clarified. The results indicate that under a short-term SC-CO2 exposure, the adsorption-induced swelling leads to the contraction of coal fractures, while the dissolution-extraction effect causes the fractures to expand. During the coal immersion process, both the adsorption-induced swelling and the dissolution-extraction effect occur simultaneously, with their intensities changing over time. Within different time intervals, they alternately dominate the evolution of coal fractures. Different metamorphic coals affect the intensity and dominant time of adsorption expansion and dissolution extraction. The adsorption and expansion dominated when lignite was immersed for 30 min, and the dissolution and extraction increased and dominated when it was immersed for 90−240 min. The adsorption and expansion were stronger when bituminous coal was immersed for 30−90 min, and the dissolution and extraction were dominant when it was immersed for 90−240 min. Adsorption and swelling dominated when anthracite was immersed for 30−150 min, and dissolution and extraction dominated when it was immersed for 150−240 min.

Abstract Background To investigate the relationship between estimated glucose disposal rate (eGDR), a surrogate indicator of insulin resistance, and atherosclerotic cardiovascular diseases (ASCVD) incidence risk. Methods This prospective cohort study utilized data from the 6026 participants from the Multi-Ethnic Study of Atherosclerosis. The eGDR (mg/kg/min) was computed as 21.158 − (0.09 × waist circumference [cm]) − (3.407 × hypertension [yes/no]) − (0.551 × HbA1c [%]). The population was categorized into four subgroups according to the quartiles (Q) of eGDR. Cox proportional hazard models were applied to assess the associations between eGDR and ASCVD incidence, and restricted cubic spine (RCS) was employed to examine the dose–response relationship. Results The mean age of participants was 63.6 ± 10.1 years, comprising 3163 (52.5%) women. Over a median follow-up duration of 14.1 years, 565 (9.4%) developed ASCVD, including 256 (4.2%) myocardial infarctions, 234 (3.9%) strokes, and 358 (5.9%) fatal coronary heart disease. Compared to the lowest quartile, the adjusted hazard ratios (95% confidence intervals) for incident ASCVD for Q2–Q4 were 0.87 (0.68−1.10), 0.63 (0.47−0.84), and 0.43 (0.30−0.64), respectively. Per 1 standard deviation increase in eGDR was associated with a 30% (HR: 0.70, 95% CI 0.60−0.80) risk reduction of ASCVD, with the subgroup analyses indicating that age and hypertension modified the association (P for interaction

Abstract Objective There is growing evidence that simultaneous bilateral open wedge high tibial osteotomy(SBOWHTO) and simultaneous bilateral unicompartmental knee arthroplasty(SBUKA) is an effective surgical treatment for bilateral medial knee osteoarthritis (MKOA). However, which intervention is more beneficial for bilateral MKOA patients remains unknown. Therefore, the aim of this study was to compare the effectiveness of these two strategies through early clinical outcomes, complication rates, and prosthetic survival. Methods The clinical data of 60 patients with bilateral MKOA admitted to the Affiliated Hospital of Qingdao University from January 2018 to December 2022 were retrospectively analyzed, and they were divided into SBOWHTO group (n = 28) and SBUKA group (n = 32) according to different treatment methods. Clinical relevant indexes, Hospital for Special Surgery (HSS) score, Knee Society Knee (KSS) score, range of motion(ROM), postoperative complications and prosthetic survival rate were compared between the two groups. Results Patients in the SBOWHTO group were followed up for 27 to 50 months, with an average of (37.18 ± 6.84) months. Patients in the SBUKA group were followed up for 24 to 59 months, with an average of (39.38 ± 9.74) months. There were no significant differences in postoperative KSS, HSS and ROM between SBOWHTO group and SBUKA group (p > 0.05). There was no significant difference in complication rate between the two groups (p = 0.721). There was no significant difference in prosthetic survival rate (p = 0.622) and prosthetic survival curve (χ2 = 0.546, p = 0.46) between the two groups. Conclusions This study compared early clinical outcomes, complication rates, and prosthesis retention rates after SBOWHTO and SBUKA, and found that the early clinical benefits of SBOWHTO and SBUKA were comparable in patients with bilateral MKOA.

To accelerate the construction of secure, green, and intelligent granaries and to enhance the level of modern management, green grain storage technologies have ushered in new developments under the backdrop of technological empowerment and the vigorous development of new production forces. This study took Wuhan National Rice Trading Center Co., Ltd. as an example reviewed and evaluated three new temperature control technologies, including photovoltaic off grid power supply technology air conditioning system, vertical thermal cortex temperature control technology in grain silos, zero energy radiation refrigeration technology, and three new insect control and insecticidal technologies by using spinosad, S-methoprene or food grade inert powder. Additionally, it was recommended to take the thermal insulation and cold insulation measures of the warehouse as the basis for the transformation of quasi low temperature warehouses, and use green grain storage technologies as the main means, such as air conditioning temperature control technology or modified atmosphere storage technology. The above new green grain storage technologies should be comprehensively applied to meet the requirements of quasi low temperature grain storage, non-fumigation grain storage, and smart grain storage. This study aimed to provide relevant references for grain storage enterprises to carry out research on the application of green grain storage new technologies.

Background:. As a systemic disease, pancreatic cancer (PC) can be treated systemically to raise the R0 resection rate and enhance patient prognosis. The best ways to assess the treatment response to systemic treatment of patients with PC are still lacking. Methods:. A total of 122 PC patients were enrolled; 25 of these patients were used as an independent testing set. According to the pathologic response, PC patients were classified into the responder and nonresponder groups. The whole tumor, core, edge, and peritumoral were segmented from the enhanced computed tomography (CT) images. Machine-learning models were created by extracting the variations in radionics features before and after therapy (delta radiomics features). Finally, we compared the performance of models based on radiomics features, changes in tumor markers, and radiologic evaluation. Results:. The model based on the core (area under curve [AUC] = 0.864) and edge features (AUC = 0.853) showed better performance than that based on the whole tumor (AUC = 0.847) or peritumoral area (AUC = 0.846). Moreover, the tumor core_edge combination model (AUC = 0.899) could better increase confidence in treatment response than using either of them alone. The accuracies of models based on changes in tumor markers and radiologic evaluation were relatively poorer than of the radiomics model. Moreover, Patients predicted to respond to therapy using the radiomics model showed a relatively longer overall survival (43 vs 27 months), although there were no significant differences (P = .063). Conclusions:. The tumor core_edge combination delta radiomics model is an effective approach to evaluate pathologic response in PC patients with systemic treatment.

Abstract The objective of this research was to explore the potential association between lipid accumulation product (LAP) and chronic kidney disease (CKD) among adult population of United States (US). Using cross-sectional data from the 2013 to 2018 National Health and Nutrition Examination Survey (NHANES), we explored the association of LAP with CKD, low estimated glomerular filtration rate (eGFR), and albuminuria. This analysis encompassed multivariate logistic regression analyses, smoothed curve fitting, subgroup analyses, and interaction tests. We found a significant positive association between higher ln-transformed LAP (LAP was transformed using a natural logarithm) and the prevalence of CKD, low-eGFR and albuminuria. Notably, this association of ln-transformed LAP with CKD and albuminuria was significantly influenced by diabetes status and sex (P for interaction 0.05). Additionally, in model 3 (adjusted for all included covariates except eGFR and urinary albumin-creatinine ratio (UACR)), a nonlinear relationship was identified between ln-transformed LAP and the presence of both CKD and albuminuria, with inflection points of 4.57 and 4.49, respectively. This indicates that this correlation is more pronounced on the right of the inflection point. In conclusion, the findings indicate a significant association between LAP and the prevalence of CKD in US adults.

Abstract Objective To compare therapeutic outcomes of predicted proliferative and nonproliferative hepatocellular carcinoma (HCC) after microwave ablation (MWA) using a previously developed imaging-based predictive model, the SMARS score. Methods This multicenter retrospective study included consecutive 635 patients with unresectable HCC who underwent MWA between August 2013 and September 2020. Patients were stratified into predicted proliferative and nonproliferative phenotypes according to the SMARS score. Overall survival (OS) and recurrence-free survival (RFS) were compared between the predicted proliferative and nonproliferative HCCs before and after propensity score matching (PSM). OS and RFS were also compared between the two groups in subgroups of tumor size smaller than 30 mm and tumor size 30–50 mm. Results The SMARS score classified 127 and 508 patients into predicted proliferative and nonproliferative HCCs, respectively. The predicted proliferative HCCs exhibited worse RFS but equivalent OS when compared with nonproliferative HCCs before (p < 0.001 for RFS; p = 0.166 for OS) and after (p < 0.001 for RFS; p = 0.456 for OS) matching. Regarding subgroups of tumor size smaller than 30 mm (p = 0.098) and tumor size 30–50 mm (p = 0.680), the OSs were similar between the two groups. However, predicted proliferative HCCs had worse RFS compared to nonproliferative HCCs in the subgroup of tumor size 30–50 mm (p < 0.001), while the RFS did not differ in the subgroup of tumor size smaller than 30 mm (p = 0.141). Conclusion Predicted proliferative HCCs have worse RFS than nonproliferative ones after MWA, especially in tumor size larger than 30 mm. However, the phenotype of the tumor may not affect the OS. Critical relevance statement Before performing microwave ablation for hepatocellular carcinoma, the tumor phenotype should be considered because it may affect the therapeutic outcome. Key Points Proliferative hepatocellular carcinoma (HCC) may be identified using the SMARS score, an imaging-based predictive model. SMARS predicted proliferative HCCs have worse recurrence-free and equivalent overall survival compared to nonproliferative HCC after microwave ablation. Tumor phenotype should be considered before performing microwave ablation. Graphical Abstract

Abstract Revealing the heterogeneity among tissues is the greatest advantage of single-cell-sequencing. Marker genes not only act as the key to correctly identify cell types, but also the bio-markers for cell-status under certain experimental imputations. Current analysis methods such as Seurat and Monocle employ algorithms which compares one cluster to all the rest and select markers according to statistical tests. This pattern brings redundant calculations and thus, results in low calculation efficiency, specificity and accuracy. To address these issues, we introduce starTracer, a novel algorithm designed to enhance the efficiency, specificity and accuracy of marker gene identification in single-cell RNA-seq data analysis. starTracer operates as an independent pipeline, which exhibits great flexibility by accepting multiple input file types. The primary output is a marker matrix, where genes are sorted by the potential to function as markers, with those exhibiting the greatest potential positioned at the top. The speed improvement ranges by 2 ~ 3 orders of magnitude compared to Seurat, as observed across three independent datasets with lower false positive rate as observed in a simulated testing dataset with ground-truth. It’s worth noting that starTracer exhibits increasing speed improvement with larger data volumes. It also excels in identifying markers in smaller clusters. These advantages solidify starTracer as an important tool for single-cell RNA-seq data, merging robust accuracy with exceptional speed.