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Highlights Additive of 1-adamantanecarbonitrile is used to strengthen the poly(ethylene oxide) based solid polymer electrolytes (SPEs). LiF-based integral cathode/SPE and Li/SPE interfaces are generated. The NMC811/Li all-solid-state performs stable cycle at 45 °C (1000, 80%).

Abstract In mammalian females, quiescent primordial follicles serve as the ovarian reserve and sustain normal ovarian function and egg production via folliculogenesis. The loss of primordial follicles causes ovarian aging. Cellular senescence, characterized by cell cycle arrest and production of the senescence-associated secretory phenotype (SASP), is associated with tissue aging. In the present study, we report that some quiescent primary oocytes in primordial follicles become senescent in adult mouse ovaries. The senescent primary oocytes share senescence markers characterized in senescent somatic cells. The senescent primary oocytes were observed in young adult mouse ovaries, remained at approximately 15% of the total primary oocytes during ovarian aging from 6 to 12 months, and accumulated in aged ovaries. Administration of a senolytic drug ABT263 to 3-month-old mice reduced the percentage of senescent primary oocytes and the transcription of the SASP factors in the ovary, in addition, led to increased numbers of primordial and total follicles and a higher rate of oocyte maturation. Our study provides experimental evidence that primary oocytes, a germline cell type that is arrested in meiosis, become senescent in adult mouse ovaries and that senescent cell clearance reduced primordial follicle loss and mitigated ovarian aging phenotypes.

Abstract Background Local recurrence after surgery and radiochemotherapy seriously affects the prognosis of locally advanced rectal cancer (LARC) patients. Studies on molecular markers related to the radiochemotherapy sensitivity of cancers have been widely carried out, which might provide valued information for clinicians to carry out individual treatment. Aim To find potential biomarkers of tumors for predicting postoperative recurrence. Methods In this study, LARC patients undergoing surgery and concurrent radiochemotherapy were enrolled. We focused on clinicopathological factors and PTEN, SIRT1, p-4E-BP1, and pS6 protein expression assessed by immunohistochemistry in 73 rectal cancer patients with local recurrence and 76 patients without local recurrence. Results The expression of PTEN was higher, while the expression of p-4E-BP1 was lower in patients without local recurrence than in patients with local recurrence. Moreover, TNM stage, lymphatic vessel invasion (LVI), PTEN and p-4E-BP1 might be independent risk factors for local recurrence after LARC surgery combined with concurrent radiochemotherapy. Conclusions This study suggests that PTEN and p-4E-BP1 might be potential biomarkers for prognostic prediction and therapeutic targets for LARC.

Abstract Background Childhoods in urban or rural environments may differentially affect the risk of neuropsychiatric disorders, possibly through memory processing and neural response to emotional stimuli. Genetic factors may not only influence individuals’ choices of residence but also modulate how the living environment affects responses to episodic memory. Methods We investigated the effects of childhood urbanicity on episodic memory in 410 adults (discovery sample) and 72 adults (replication sample) with comparable socioeconomic statuses in Beijing, China, distinguishing between those with rural backgrounds (resided in rural areas before age 12 and relocated to urban areas at or after age 12) and urban backgrounds (resided in cities before age 12). We examined the effect of childhood urbanicity on brain function across encoding and retrieval sessions using an fMRI episodic memory paradigm involving the processing of neutral or aversive pictures. Moreover, genetic association analyses were conducted to understand the potential genetic underpinnings that might contribute to memory processing and neural mechanisms influenced by early-life urban or rural environments. Results Episodic memory retrieval accuracy for more difficult neutral stimuli was similar between those with urban and rural childhoods, whereas aversive stimuli elicited higher retrieval accuracy in the urban group (P = 0.023). For aversive stimuli, subjects with urban childhood had relatively decreased engagement of the striatum at encoding and decreased engagement of the hippocampus at retrieval. This more efficient striatal encoding of aversive stimuli in those with urban childhoods was associated with common variation in neurotrophic tyrosine kinase receptor type 2 (NTRK2) (right striatum: P = 1.58×10−6). These findings were confirmed in the replication sample. Conclusions We suggest that this differential striatal processing of aversive stimuli observed in individuals with urban or rural childhoods may represent mechanisms by which childhood urbanicity may affect brain circuits, heightening behavioral responses to negative stressors associated with urban environments. NTRK2-associated neural processes in the striatum may play a role in these processes.

Abstract Pre-surgery differential diagnosis is valuable for personalized treatment planning in intramedullary spinal cord tumors. This study assessed the performance of sequencing cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) for differential diagnosis of these tumors. Prospectively enrolling 45 patients with intramedullary spinal cord lesions, including diffuse midline glioma (DMG), H3K27-altered (14/45), glioblastoma (1/45), H3-wildtype-astrocytoma (10/45), ependymoma (11/45), and other lesions (9/45), CSF samples were collected via lumbar puncture (41/45), intraoperative extraction (3/45), and Ommaya reservoir (1/45). Then, these samples underwent targeted sequencing along with paired tissue DNA. DMG, H3K27-altered patients exhibited a higher ctDNA positivity (85.7%, 12/14) compared to patients with H3-wildtype-astrocytoma (0/8, P = 0.0003), ependymoma (2/10, P = 0.003), and glioneuronal tumor (0/3, P = 0.009). The histological-grade-IV (P = 0.0027), Ki-67 index ≥10% (P = 0.014), and tumor reaching spinal cord surface (P = 0.012) are also associated with higher ctDNA positivity. Interestingly, for patients with TERT promoter mutant tumors, TERT mutation was detectable in the CSF cfDNA of one DMG case, but not other five cases with histological-grade-II tumors. Shared copy number variants were exclusively observed in DMG, H3K27-altered, and showed a strong correlation (Correlation = 0.95) between CSF and tissue. Finally, H3K27M mutations in CSF exhibited high diagnostic efficiency for DMG, H3K27-altered (Sensitivity = 85.7%, Specificity = 100.0%, AUC = 0.929). Notably, H3K27M was detectable in CSF from patients with recurrent tumors, making it easily applicable for postoperative monitoring. In conclusion, the molecular profile from ctDNA released into CSF of malignant tumors was more frequently detected compared to relatively benign ones. Sequencing of ctDNA in CSF exhibited high efficiency for the differential diagnosis of DMG, H3K27-altered.

Separation flow in a curved duct is a common phenomenon in engineering applications, and it highly contributes to the performance of fluid machinery. Accurate prediction of curved duct flows using the computational fluid dynamics method remains a challenge due to the limitations of turbulence modeling. Hence, the high-fidelity method of the delayed detached eddy simulation (DDES) approach is employed to simulate the U-duct flow with a Reynolds number of 105. The DDES results are compared with experimental data from the study by Monson et al. (1990) and analyzed in detail. The Q-criterion is defined to analyze the vortex structures and study the mechanism in the flow separation region. Discussions are made on turbulence characteristics, including turbulence energy spectra, helicity density, and turbulence anisotropy in the U-duct flow. Results indicate that the regions near the wall and within flow separation are highly anisotropic. The turbulence near the wall region is in a two-dimensional state, and the turbulence within the flow separation region is in a “rod-like” state.

Human regulatory T cells (Treg) suppress other immune cells. Their dysfunction contributes to the pathophysiology of autoimmune diseases, including type 1 diabetes (T1D). Infusion of Tregs is being clinically evaluated as a novel way to prevent or treat T1D. Genetic modification of Tregs, most notably through the introduction of a chimeric antigen receptor (CAR) targeting Tregs to pancreatic islets, may improve their efficacy. We evaluated CAR targeting of human Tregs to monocytes, a human β cell line and human islet β cells in vitro. Targeting of HLA-A2-CAR (A2-CAR) bulk Tregs to HLA-A2+ cells resulted in dichotomous cytotoxic killing of human monocytes and islet β cells. In exploring subsets and mechanisms that may explain this pattern, we found that CD39 expression segregated CAR Treg cytotoxicity. CAR Tregs from individuals with more CD39low/- Tregs and from individuals with genetic polymorphism associated with lower CD39 expression (rs10748643) had more cytotoxicity. Isolated CD39− CAR Tregs had elevated granzyme B expression and cytotoxicity compared to the CD39+ CAR Treg subset. Genetic overexpression of CD39 in CD39low CAR Tregs reduced their cytotoxicity. Importantly, β cells upregulated protein surface expression of PD-L1 and PD-L2 in response to A2-CAR Tregs. Blockade of PD-L1/PD-L2 increased β cell death in A2-CAR Treg co-cultures suggesting that the PD-1/PD-L1 pathway is important in protecting islet β cells in the setting of CAR immunotherapy. In summary, introduction of CAR can enhance biological differences in subsets of Tregs. CD39+ Tregs represent a safer choice for CAR Treg therapies targeting tissues for tolerance induction.

Plant protection unmanned aerial vehicles (UAVs) have become popular in mountain orchards, but due to the differences in planting structures, the chances of heavy spraying, missed spraying and pesticide drift are increasing. To mitigate the adverse effects of these phenomena, it is necessary to clarify the effective deposition range of aerial spray droplets. This study proposed an effective spray swath determination method for the effective spraying range of mountainous orchards with UAVs equipped with a mist nozzle (bilateral 1% coverage). This approach focused on exploring the effects of flight height (unidirectional flight modes of 2, 3 and 4 m), spray nozzle atomization performance (reciprocating flight modes of 20, 30 and 40 µm) and flight route (treetop flying and inter-row flying) on the spraying range in a mountain setting. In addition, the study analysed the relationship between the droplet-size spectrum and the effective swath position. The results showed that it is feasible to use the bilateral 1% coverage evaluation method to determine the effective spray swath of a UAV adapted with a mist nozzle for aerial operation in a mountainous Nangguo Pear orchard. With the increase in UAV flight height (2–4 m), the effective unidirectional spray swath also increased, and with the increase in atomization level (20–40 μm), the effective reciprocating spray swath showed a decreasing trend. Moreover, the average effective swath width measured by the UAV for treetop flight was greater than that measured for inter-row flight. The study also found that the proportion of small droplets (droplet size less than 100 µm) below the UAV route was lower (approximately 50%) than along the sides of the route (approximately 80%), and the spray swath was not symmetrically distributed along the flight route but shifted laterally by approximately 3 to 4 m in the downhill direction.

ABSTRACT Our study aims to investigate the impact of probiotic consumption during pregnancy on gut microbiota functional diversity in healthy pregnant women. Thirty-two pregnant women were randomly assigned to two groups. The probiotic group (PG) consisted of pregnant women who consumed triple viable Bifidobacterium longum, Lactobacillus delbrueckii bulgaricus, and Streptococcus thermophilus tablets from the 32nd week of pregnancy until delivery. The functional profiles of the gut microbiota were predicted through high-throughput 16S rRNA sequencing results using PICRUSt software and referencing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. In the gut microbiota of the PG, the genera Blautia and Ruminococcus, as well as the species Subdoligranulum, showed significantly higher relative abundances compared to the control group (CG) (P < 0.05). At Level 1 of the KEGG signaling pathways, there was a significant reduction in the functional genes of the gut microbiota involved in Organismal Systems in the PG (P < 0.05). In Level 2 of the KEGG signaling pathways, there was a significant reduction in the functional genes of the gut microbiota involved in Infectious Disease in the PG (P < 0.05). In Level 3 of the KEGG signaling pathways, the PG exhibited a significant increase in the functional genes of the gut microbiota involved in ABC transporters, Oxidative phosphorylation, Folate biosynthesis, and Biotin metabolism (P < 0.05). The CG showed a significant increase in the functional genes related to Cysteine and methionine metabolism, Vitamin B6 metabolism, Tuberculosis, and Vibrio cholerae pathogenic cycle (P < 0.05). In conclusion, our findings suggest that probiotic supplementation during pregnancy has a significant impact on functional metabolism in healthy pregnant women.IMPORTANCEProbiotics are considered beneficial to human health. There is limited understanding of how probiotic consumption during pregnancy affects the functional diversity of the gut microbiota. The aim of our study is to investigate the impact of probiotic consumption during pregnancy on the functional diversity of the gut microbiota. Our findings suggest that probiotic supplementation during pregnancy has a significant impact on functional metabolism. This could potentially open up new avenues for preventing various pregnancy-related complications. This also provides new insights into the effects of probiotic consumption during pregnancy on the gut microbiota and offers a convenient method for exploring the potential mechanisms underlying the impact of probiotics on the gut microbiota of pregnant women.

Abstract The availability of an alternative and efficient genetic editing technology is critical for fundamental research and strain improvement engineering of Streptomyces species, which are prolific producers of complex secondary metabolites with significant pharmaceutical activities. The mobile group II introns are retrotransposons that employ activities of catalytic intron RNAs and intron‐encoded reverse transcriptase to precisely insert into DNA target sites through a mechanism known as retrohoming. We here developed a group II intron‐based gene editing tool to achieve precise chromosomal gene insertion in Streptomyces. Moreover, by repressing the potential competition of RecA‐dependent homologous recombination, we enhanced site‐specific insertion efficiency of this tool to 2.38%. Subsequently, we demonstrated the application of this tool by screening and characterizing the secondary metabolite biosynthetic gene cluster (BGC) responsible for synthesizing the red pigment in Streptomyces roseosporus. Accompanied with identifying and inactivating this BGC, we observed that the impair of this cluster promoted cell growth and daptomycin production. Additionally, we applied this tool to activate silent jadomycin BGC in Streptomyces venezuelae. Overall, this work demonstrates the potential of this method as an alternative tool for genetic engineering and cryptic natural product mining in Streptomyces species.

Transglutaminase (EC 2.3.2.13, TGase), an enzyme that catalyzes the formation of covalent cross-links between protein or peptide molecules, plays a critical role in commercial food processing, medicine, and textiles. TGase from Streptomyces is the sole commercial enzyme preparation for cross-linking proteins. In this study, we revealed that the SOS response repressor protein LexA in Streptomyces mobaraensis not only triggers morphological development but also enhances TGase synthesis. The absence of lexA significantly diminished TGase production and sporulation. Although LexA does not bind directly to the promoter region of the TGase gene, it indirectly stimulates transcription of the tga gene, which encodes TGase. Furthermore, LexA directly enhances the expression of genes associated with protein synthesis and transcription factors, thus favorably influencing TGase synthesis at both the transcriptional and posttranscriptional levels. Moreover, LexA activates four crucial genes involved in morphological differentiation, promoting spore maturation. Overall, our findings suggest that LexA plays a dual role as a master regulator of the SOS response and a significant contributor to TGase regulation and certain aspects of secondary metabolism, offering insights into the cellular functions of LexA and facilitating the strategic engineering of TGase overproducers.

Introduction: Human topoisomerase 1 (TOP1) is an important target of various anticancer compounds. The design and discovery of inhibitors targeting TOP1 are of great significance for the development of anticancer drugs. Evodiamine and thieno [2,3-d] pyridine hybrids show potential antitumor activity. Herein, the anti-gastric cancer activities of these hybrids were investigated.Methods: The inhibitory effects of different concentrations of ten evodiamine derivatives on the gastric cancer cell line SGC-7901 were assessed using a methyl thiazolyl tetrazolium assay. Compounds EVO-1 and EVO-6 strongly inhibited gastric cancer cell proliferation, with inhibition rates of 81.17% ± 5.08% and 80.92% ± 2.75%, respectively. To discover the relationship between the structure and activity of these two derivatives, density functional theory was used to investigate their optimized geometries, natural population charges, frontier molecular orbitals, and molecular electrostatic potentials. To clarify their anti-gastric cancer mechanisms, molecular docking, molecular dynamics simulations, and binding free energy calculations were performed against TOP1.Results: The results demonstrated that these compounds could intercalate into the cleaved DNA-binding site to form a TOP1–DNA–ligand ternary complex, and the ligand remained secure at the cleaved DNA-binding site to form a stable ternary complex. As the binding free energy of compound EVO-1 with TOP1 (−38.33 kcal·mol−1) was lower than that of compound EVO-6 (−33.25 kcal·mol−1), compound EVO-1 could be a more potent anti-gastric cancer agent than compound EVO-6.Discussion: Thus, compound EVO-1 could be a promising anti-gastric cancer drug candidate. This study may facilitate the design and development of novel TOP1 inhibitors.

Invariant Natural Killer T cell therapy is an emerging platform of immunotherapy for cancer treatment. This unique cell population is a promising candidate for cell therapy for cancer treatment because of its inherent cytotoxicity against CD1d positive cancers as well as its ability to induce host CD8 T cell cross priming. Substantial evidence supports that iNKT cells can modulate myelomonocytic populations in the tumor microenvironment to ameliorate immune dysregulation to antagonize tumor progression. iNKT cells can also protect from graft-versus-host disease (GVHD) through several mechanisms, including the expansion of regulatory T cells (Treg). Ultimately, iNKT cell-based therapy can retain antitumor activity while providing protection against GVHD simultaneously. Therefore, these biological properties render iNKT cells as a promising “off-the-shelf” therapy for diverse hematological malignancies and possible solid tumors. Further the introduction of a chimeric antigen recetor (CAR) can further target iNKT cells and enhance function. We foresee that improved vector design and other strategies such as combinatorial treatments with small molecules or immune checkpoint inhibitors could improve CAR iNKT in vivo persistence, functionality and leverage anti-tumor activity along with the abatement of iNKT cell dysfunction or exhaustion.

Abstract Objective To evaluate the efficacy and safety of regorafenib monotherapy or in combination with immune-checkpoint inhibitor while treating Chinese patients with metastatic colorectal cancer (mCRC): a real-world study. Methods The data of patients with metastatic colorectal cancer who received regorafenib-containing regimen as the third or later line treatment at ten Chinese hospitals from Aug 2017 to Jun 2020 were retrospectively analyzed, including dosing details, survival data as well as adverse events. Survival analysis was further performed for patients administrated with regorafenib monotherapy and combined with an immune-checkpoint inhibitor based on Kaplan-Meier and Cox regression methods. The primary endpoint was overall survival. Results A total of 537 patients were included with a median age of 61, among whom 376 received regorafenib monotherapy and 245 received regorafenib combined with immune-checkpoint inhibitors. The clinicopathological characteristics of the two groups at baseline were mainly balanced. No significant difference in progression-free survival (PFS) was observed in patients receiving regorafenib monotherapy or combination therapy (3.8 vs. 5.5 months, p = 0.170). In contrast, patients receiving combination therapy had a more prolonged overall survival (OS) than those receiving regorafenib monotherapy (13.5 vs. 10.0 months, p = 0.001). The treatment regimen and regorafenib dosage were significant prognostic factors in the multivariate analysis. Significant benefits in PFS and OS were achieved in KRAS mutant and anti-angiogenesis treatment-naïve subgroups receiving combination therapy compared to monotherapy. No apparent increase was recorded in treatment-related adverse events in patients receiving combination therapy. Conclusion Regorafenib plus an immune-checkpoint inhibitor has already been a widely adopted strategy in the later-line treatment for mCRC in the real world. The combination therapy yielded a significantly prolonged overall survival than regorafenib alone, with a manageable safety profile in Chinese patients, and warrants further investigation. Trial registration ClinicalTrials.gov Identifier: NCT04835324. Registered 6th April 2021.

Aiming at the problems that multiplex influencing factors and strong uncertainty in distribution network load caused by the capacity accumulation of distributed generation and new loads, a load prediction method using memory neural network and curve shape correction is proposed. In load peak prediction, the maximum information coefficient is applied to calculate the nonlinear correlation between load peak and influencing factors, so as to select the input features. Considering the long-term and short-term autocorrelation in load peak sequence and the different correlation between input features and load peak, the load peak prediction model is established with the Attention mechanism and bidirectional long-short term memory (BiLSTM) neural network. In load per-unit curve prediction, a prediction model is established by combining similar day and adjacent day through the reciprocal error method. In view of the non-stationary characteristics of prediction deviation, the complete ensemble empirical mode decomposition with adaptive noise and BiLSTM network are used to establish an error prediction model to correct the curve shape. The validity of the proposed model is verified by an example of regional power grid load of a city in northern China.

Abstract Background Continuing Medical Education (CME) is an important part of the training process for health workers worldwide. In China, training in Traditional Chinese Medicine (TCM) not only improves the expertise of medical workers, but also supports the Chinese Government’s policy of promoting TCM as an equal treatment to western medicine. CME, including learning Traditional Chinese Medicine Technologies (TCMTs), perform poorly and research into the motivation of health workers to engage in CME is urgently required. Using a discrete choice experiment, this study assessed the CME learning preferences of primary health workers, using TCMT as a case study of CME programs. Methods We conducted a discrete choice experiment among health workers in Shandong Province, Guizhou Province, and Henan provinces from July 1, 2021 to October 1, 2022 on the TCMT learning preferences of primary health workers. The mixed logit model and latent class analysis model were used to analyze primary health workers’ TCMT learning preferences. Results A total of 1,063 respondents participated in this study, of which 1,001 (94.2%) passed the consistency test and formed the final sample. Our key finding was that there were three distinct classes of TCMT learners. Overall, the relative importance of the seven attributes impacting the learning of TCMTs were: learning expenses, expected TCMT efficacy, TCMT learning difficulty, TCMT mode of learning, TCMT type, time required to learn, and expected frequency of TCMT use. However, these attributes differed significantly across the three distinct classes of TCMT learners. Infrequent users (class 1) were concerned with learning expenses and learning difficulty; workaholics (class 2) focused on the mode of learning; and pragmatists (class 3) paid more attention to the expected TCMT efficacy and the expected frequency of TCMT use. We recommend targeted strategies to motivate TCMT learning suited to the requirements of each class of TCMT learners. Conclusion Rather than a single TCMT medical education program for primary health workers, CME programs should be targeted at different classes of TCMT learners.

A novel Eu(tta)3([4,4′-(t-bu)2-2,2′-bpy)] complex (tta-thenoyltrifluoroacetone), a ratiometric luminescent-based optical sensor for the quantitative determination of aluminum ion, is synthesized and characterized using XRD and 1H NMR. The XRD data reveal the slightly distorted octahedral structure. The complex displays a bright red emission at 613 nm in methanol which is characteristic of europium (III) complexes. Upon the addition of Al3+ ions, the red emission disappears, and a new blue emission at 398 nm emerges, manifesting the ratiometric nature of the complex. The turn-off of the red emission and turn-on of the blue emission are attributed to Eu-Al trans-metalation, as supported by Raman data that show the emergence of Al-O vibrations at 418, 495, and 608 cm−1 concomitant with the disappearance of Eu-O and Eu-N bond vibrations. Most aluminum sensors are known to suffer from interferences from other metals including Cu2+, Co2+, and Cd2+. However, the sensor reported here is tested for 11 common cations and shows no interference on sensitivity. To the best of our knowledge, this is the first known Eu-based luminescence sensor that successfully exhibited the ability to detect aluminum ions in ppb levels in aqueous environments. The calculated Al3+ binding constant is 2.496 × 103 ± 172. The complex shows a linear relationship in the range of 0–47.6 ppb (1.76 × 10−6 M) Al3+ and the limit of detection (LOD) is 4.79 ppb (1.77 × 10−7 M) in MeOH. ICP-OES is used for validation of the sensor complex in water and then it was used for quantitative detection of Al3+ ions in water as a real-life application. The complex can accurately detect Al3+ ions in the range of 4.97–24.9 ppb (1.84 × 10−7 M–9.2 × 10−7 M) with an LOD of 8.11 ppb (2.99 × 10−7 M). Considering that the aluminum ion serves no recognized function within the human body, its accumulation can lead to severe neurological disorders, including Parkinson’s and Alzheimer’s diseases. With the LOD value significantly lower than the WHO-recommended maximum permissible level of 200 ppb for aluminum in drinking water, even without high-power laser-aided signal enhancement, the sensor shows promise for detecting trace amounts of aluminum contamination in water. Therefore, it can significantly aid in the monitoring of even the smallest aluminum ion contamination in drinking water, industrial effluents, and natural water bodies.

Abstract Background Sapovirus (SaV) infection is increasing globally. Concurrently, several SaV-outbreaks were observed in children of Zhejiang province, China, in recent years, In this study, the genotypes of Sapovirus from seven outbreaks in the Zhejiang province were analysed. Methods A total of 105 faecal samples were collected from children aged between 4 and 17 years from the Zhejiang Provincial Center for Disease Control and Prevention between October 2021 and February 2023. Genotypes were processed using reverse transcription polymerase chain reaction and Sanger sequencing, while next-generation sequencing was used to generate a complete viral genome. Deduced amino acid sequences were analysed to detect VP1 gene mutations. Results In total, 60 SaV-positive patients were detected at a 57.14% (60/105) positivity rate. Positive rates in the seven outbreaks were: 22.22% (2/9), 15.00% (3/20), 93.10% (27/29), 84.21% (16/19), 28.57% (2/7), 53.33% (8/15) and 33.33% (2/6), respectively. Four genotypes were identified in the seven outbreaks, of which, GI.1 accounted for 14.29% (1/7), GI.2 accounted for 14.29% (1/7), GI.6 and GII.5 accounted for 14.29% (1/7), and GI.6 accounted for 57.14% (4/7). All patients were children and outbreaks predominantly occurred in primary schools and during cold seasons. Additionally, the complete sequence from the GI.6 outbreak strain showed high homology (identity: 99.99%) with few common substitutions (Y300S, N302S and L8M) in VP1 protein. Conclusions SaV genotype diversity was observed in the seven outbreaks, with GI.6 being the main SaV genotype in Zhejiang province. It demonstrated high homology and may provide a platform for SaV prevention and control measures.

Hydrofoil, as the basic shape of the fluid blade, is widely used in fluid transport and energy conversion. However, friction resistance and pressure differential resistance are generated in the hydrofoil flow process, resulting in substantial energy consumption and negatively affecting the economy. On this basis, we propose two drag-reducing structures based on Clark-Y hydrofoil. In the design process of the jet structure, we considered the bionic jet velocity, jet angle and jet structure position as the design parameters and obtained the optimal jet structure by using Taguchi method. Finally, the two schemes (Clark-Yori and Clark-Yopt) are numerically simulated using large eddy simulation. Results show that when Ujet = 1.44 m/s, θ = 3° and x = 18.6 mm, the jet structure can play a significant drag reduction effect. Compared with Clark-Yori, the drag coefficient of Clark-Yopt is reduced by 26.5%, and the lift drag ratio is increased by 16.4%. Compared with Clark-Yori, Clark-Yopt can reduce the wall shear stress of the leading edge of the hydrofoil, thereby diminishing the frictional resistance. Meanwhile, the jet structure can effectively balance the area of the low-pressure region on the suction side of the hydrofoil, significantly reducing the pressure differential resistance. Clark-Yopt can accelerate the vortex collapse that decreases turbulence intensity and turbulence resistance. Moreover, it can effectively block the near-wall reflux of hydrofoil and reduce the internal friction between the reflux and the main flow.

Phase modulation of noble metal alloys (NMAs) is critically important in nanoscience since the distinct atomic arrangements can largely determine their physicochemical properties. However, the precise modulation of NMAs is formidably challenging, because thermodynamically stable phases are generally preferential compared to those metastable ones. Herein, we proposed a potential energy trapping strategy for phase modulation of Pd–Te alloys with solvents. Thereinto, ethylene glycol can increase the energy barrier for both Pd leaching and Te introduction, forming metastable Pd20Te7 phase. Inversely, N, N-dimethylformamide is unable to trap metastable phase, inducing the phase evolution to thermodynamically stable PdTe phase, and the precise phase modulation was realized including Pd20Te7, PdTe and PdTe2 phases. The Pd–Te alloys displayed phase-dependent formic acid oxidation catalytic performance with PdTe phase showing the best. This work proposes a strategy for creating metastable phase with potential energy trap, which may deepen the understanding of phase engineering for noble metal-based nanocrystals.

BackgroundWhether sarcopenic obesity had unfavorable effect on survival of peritoneal dialysis (PD) patients is unknown. We aimed to investigate the association between sarcopenic obesity and survival in PD patients.MethodsThis was a prospective observational study. Eligible PD patients from November 2016 to December 2017 were enrolled and followed until August 31, 2023. Sarcopenia was defined following the recommendations of the Asian Working Group for Sarcopenia (AWGS) as low appendicular skeletal muscle mass index (ASMI) and handgrip strength (HGS). Obesity was defined using the percentage of body fat (PBF). Survival analysis was conducted using the Kaplan–Meier and log-rank test. The Cox regression and the cumulative incidence competing risk (CICR) analyzes were used to investigate the association between sarcopenic obesity and all-cause mortality.ResultsA total of 223 patients were enrolled with 133 (59.6%) males, a median age of 57.5 (44.6, 65.7) years, a median dialysis vintage of 20.3 (6.4, 57.7) months and 48 (21.5%) who had comorbid diabetes mellitus. Among them, 46 (20.6%) patients were sarcopenic, and 25 (11.2%) patients were diagnosed with sarcopenic obesity. After followed up for 51.6 (25.6, 73.9) months, the Kaplan–Meier curve showed the sarcopenic obesity (log-rank = 13.527, p

Abstract Quasi‐solid‐state electrolytes (QSSEs) based on ionic liquids are recognized as one of the frontrunners of electrolytes for ensuring the safety and high energy density of next‐generation lithium batteries. However, the incapacity of such systems to meet the performance demands of batteries is significantly subject to the properties of the electrolyte and the intricacies of related interfacial processes. Recently, we have designed a high‐performing pyrrolidinium bis(trifluoromethylsulfonyl)imide (Py14TFSI) based QSSE (Py‐Gel), with introducing LiBF4 and LiCl, which served as a system for probing the dynamic Li deposition mechanism. Herein, we focus on understanding the mechanisms of Py‐Gel formation and examining the chemistry and structure as well as the properties of the solid‐electrolyte interphases (SEIs) formed in the Py‐Gel and their influences on Li deposition. Spectroscopic characterizations suggest the existence of a cross‐linked structure in Py‐Gel, for which multiple intermolecular/intramolecular hydrogen bondings and ionic coulumbic interactions among Py cations, TFSI− anions, and Li salts are responsible. The Py‐Gel electrolyte exhibits exceptional electrical properties at room temperature. Different SEIs are prepared in the Py‐Gel via electrochemical protocols to elucidate that the synergy between a well‐featured electrolyte and an outstanding SEI is vital for stable cycling of Li metal anodes in such a QSSE.

Clock noise is one of the dominant noises in the space-borne gravitational wave (GW) detection. To suppress this noise, the clock noise-calibrated time-delay-interferometry (TDI) technique is proposed. In this technique, an inter-spacecraft clock tone transfer chain is necessary to obtain the comparison information of the clock noises in two spacecraft, during which an electro-optic-modulator (EOM) is critical and used to modulate the clock noise to the laser phase. Since the EOM sideband modulation process introduces the extra modulation noise, it may limit the experimental demonstration of the suppression effect of the clock noise, and further affect the space-borne GW detection. To solve this problem, it is significant to put forward the modulation noise requirement and test whether the experimental components meet or not. In this work, based on the typical Michelson TDI algorithm and the fundamental noise requirement of GW detectors, the analytic expression of the modulation noise requirement is strictly derived, relaxing the specification compared to the commonly used rough assessments. Furthermore, a method is provided to experimentally test EOM modulation noise, and a commercial EOM (iXblue-NIR-10 GHz) is tested. The experimental results show that it can meet the requirement of the typical GW detection mission LISA in the whole scientific frequency bandwidth by taking the optimal combination of the data streams.

Abstract Urbanization is a trend lasting for more than one century worldwide. Four hundred ninety male and female adult Chinese Han participants with different urban and rural childhoods were included in this study. Early-life urban environment was found benefit for total grey matter volume (GMV), dorsolateral prefrontal cortex (DLPFC) GMV, temporal pole (TP) GMV and cognition function, and negatively correlated with medial prefrontal cortex (MPFC) GMV. Regression analysis showed that maternal education was a protective factor for total and DLPFC GMVs, while having siblings was better for MPFC GMV. Total, DLPFC and TP GMVs acts mediation effects between childhood urbanicity and different cognitive domains. These findings may suggest some pros and cons on brain structure associated with childhood urbanicity and related environmental factors.

Abstract Thermophilic cell factories have remarkably broad potential for industrial applications, but are limited by a lack of genetic manipulation tools and recalcitrance to transformation. Here, we identify a thermophilic type I-B CRISPR-Cas system from Parageobacillus thermoglucosidasius and find it displays highly efficient transcriptional repression or DNA cleavage activity that can be switched by adjusting crRNA length to less than or greater than 26 bp, respectively, without ablating Cas3 nuclease. We then develop an orthogonal tool for genome editing and transcriptional repression using this type I-B system in both thermophile and mesophile hosts. Empowered by this tool, we design a strategy to screen the genome-scale targets involved in transformation efficiency and established dynamically controlled supercompetent P. thermoglucosidasius cells with high efficiency ( ~ 108 CFU/μg DNA) by temporal multiplexed repression. We also demonstrate the construction of thermophilic riboflavin cell factory with hitherto highest titers in high temperature fermentation by genome-scale identification and combinatorial manipulation of multiple targets. This work enables diverse high-efficiency genetic manipulation in P. thermoglucosidasius and facilitates the engineering of thermophilic cell factories.

UAV swarm passive positioning technology only requires the reception of electromagnetic signals to achieve the positioning and tracking of radiation sources. It avoids the active positioning strategy that requires active emission of signals and has the advantages of good concealment, long acting distance, and strong anti-interference ability, which has received more and more attention. In this paper, we propose a new UAV swarm formation flight method based on pure azimuth passive positioning. Specifically, we propose a two-circle positioning model, which describes the positional deviation of the receiving UAV using trigonometric functions relative to the target in polar coordinates. Furthermore, we design a two-step adjustment strategy that enables the receiving UAV to reach the target position efficiently. Based on the above design, we constructed an optimized UAV swarm formation scheme. In experiments with UAV numbers of 8 and 20, compared to the representative comparison strategy, the proposed UAV formation scheme reduces the total length of the UAV formation by 34.76% and 55.34%, respectively. It demonstrates the effectiveness of the proposed method in the application of assigning target positions to UAV swarms.

BackgroundThe community characteristics of the gut microbiota are not well defined and are not as widely studied as the functions of individual bacteria. This study aims to investigate the community composition of intestinal flora in women of childbearing age by conducting cluster analysis of gut microbiota and analyzing the relationship between different clusters and immune status.MethodsA total of 45 women of childbearing age were recruited in the study, including 15 non-pregnant women and 30 women in late pregnancy, and stool samples were collected twice during the third trimester, specifically at 32 weeks and at full term. The gut microbiota data was analyzed using 16S rRNA amplicon sequencing. Partitioning Around Medoids algorithm was employed to assess microbial clustering patterns. Microbial network for each cluster was performed and plasm cytokines were measured to analyze the relationship between specific genera and immune state in clusters.ResultsThere were three distinct clusters of intestinal community composition in women of childbearing age. Cluster 1 (PAM_1) was characterized by a high abundance of Bacteroides, while cluster 2 (PAM_2) showed higher levels of Bifidobacterium and Blautia, along with a significantly increased Firmicutes to Bacteroidota ratio. Cluster 3 (PAM_3) displayed a high abundance of Escherichia-shigella. PAM_1 was the most dominant cluster in non-pregnant women, and this dominant cluster was also one of the main in late pregnancy. At full term, the majority of subjects retained the same cluster as at 32 weeks, while a few experienced a shift. The microbial correlation networks differed across the three clusters, with PAM_1 exhibiting higher modularity and fewer connections. Analysis of the correlation between genera and plasma cytokines showed significant differences in their associations with cytokines between pregnancy and nonpregnancy within the same cluster, and the same genera had different effects in different clusters.ConclusionWomen of childbearing age exhibit three distribution patterns of gut microbiota, and the intestinal clusters reshaped during late pregnancy in a small population. Different clusters may have diverse immunomodulatory effects in different physiological states. When studying the gut microbiome during pregnancy, it is crucial to consider the cluster differences within healthy women.

IntroductionNon-suicidal self-injury (NSSI) is highly prevalent in depression, and is associated with psychosocial factors, emotion dysregulation, and strategies of cognitive emotion regulation. However, the internal combination and interactions of these risk factors in depression remain unclear.MethodsData from 122 patients with depression, including 56 with NSSI and 66 without NSSI, were analyzed. Self-rating scales were used to assess psychosocial factors, emotion dysregulation, and cognitive regulation strategies. Sparse partial least squares discriminant analysis (sPLS-DA) was employed to explore internal combinations in each profile. A moderated mediation model was applied to examine their interactional relationship.ResultsThe results identified an NSSI-related psychosocial profile characterized by high neuroticism, childhood trauma, poor family functioning, and low psychological resilience. Emotion dysregulation, including high levels of alexithymia, anhedonia, and emotion regulation difficulties, mediated the association between this psychosocial profile and NSSI. The mediated effect was further moderated by maladaptive cognitive regulation strategies.LimitationsLack of sufficient information on NSSI frequency and severity. Relatively small sample size for discussing the impact of gender and age of depressive patients with NSSI.ConclusionThese findings hold important implications for the prevention, treatment, and rehabilitation of NSSI.

Abstract Oxidation of renewable polyol/sugar into formic acid using molecular O2 over heterogeneous catalysts is still challenging due to the insufficient activation of both O2 and organic substrates on coordination-saturated metal oxides. In this study, we develop a defective MnO2 catalyst through a coordination number reduction strategy to enhance the aerobic oxidation of various polyols/sugars to formic acid. Compared to common MnO2, the tri-coordinated Mn in the defective MnO2 catalyst displays the electronic reconstruction of surface oxygen charge state and rich surface oxygen vacancies. These oxygen vacancies create more Mnδ+ Lewis acid site together with nearby oxygen as Lewis base sites. This combined structure behaves much like Frustrated Lewis pairs, serving to facilitate the activation of O2, as well as C–C and C–H bonds. As a result, the defective MnO2 catalyst shows high catalytic activity (turnover frequency: 113.5 h−1) and formic acid yield (>80%) comparable to noble metal catalysts for glycerol oxidation. The catalytic system is further extended to the oxidation of other polyols/sugars to formic acid with excellent catalytic performance.

Abstract Microbial anaerobic oxidation of methane coupled to the reduction of Mn(IV)-oxides, typically MnO2, derived from continental weathering and riverine transport has been proposed as a globally important sink of methane. However, the potential role of hydrothermal Mn(IV) oxide-rich sediments as a methane sink, and the mechanisms of underpinning methane oxidation at high-temperature hydrothermal fields remain poorly understood. Here, we report the occurrence of almost pure rhodochrosite with extremely negative δ13CPDB values (as low as –76.4‰) in direct association with hausmannite formed through hydrothermal activity in the Late Triassic Heqing Mn deposit in Southern China. Based on detailed petrography and geochemistry, this rhodochrosite is interpreted as the result of the thermochemical oxidation of methane by hausmannite during early diagenesis. Given high hydrothermal Mn2+ and CH4 release coupled to low sulfate concentration observed in the Archean oceans, we propose that hydrothermal Mn(IV) oxides may have been effective methane sinks in Earth’s ancient oceans.

Since 1998, the Au–O–Ti4+ sites of Au/Ti-based catalysts have been widely accepted as the active sites for propene epoxidation with H2 and O2 at a relatively high temperature, although they are limited by poor H2 efficiency. Herein, we demonstrate a novel Au–O–Ti3+ active site aiming at low-temperature propene epoxidation. Notably, this active site results in a sharp shift in the optimum temperature, from 200 to 138 °C, and allows the catalyst to maintain an unprecedented H2 efficiency of 43.6%, a high propylene oxide (PO) selectivity of 90.7%, and a stability of over 100 h. The Au–O–coordinatively unsaturated Ti3+ active site is quantitatively constructed by tuning the amount of Si–OH and Bu3NH+ in post-treated silicalite-1 seeds. Through operando ultraviolet–visible (UV–vis) spectroscopy, the dynamic evolution of the Ti–OOH intermediate was investigated. It was found that the Ti–OOH generation rate is higher on Au–O–Ti3+ than on conventional Au–O–Ti4+ sites. Moreover, ammonia temperature-programmed desorption (NH3-TPD) and X-ray photoelectron spectroscopy (XPS) characterizations, together with density-functional theory (DFT) calculations, demonstrated that the coordinatively unsaturated Ti3+ sites promote electron transfer between Au and Ti3+, thereby enhancing the O2 adsorption ability of the catalyst and promoting the in situ formation of H2O2 and the Ti–OOH intermediate, even at a low temperature. The insights and methodology reported here not only shed new light on maximizing H2 efficiency over a coordinatively unsaturated Ti3+ structure of titanium silicate-1 but also open up new opportunities for industrial direct gas-phase propene epoxidation in a low temperature range.

Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10−15 g/L, and the quantitative limit reached 1.0 × 10−13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (KD) of 5.701 × 10−11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a KD of up to 4.181 × 10−10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.

Abstract Consciousness arises from the spatiotemporal neural dynamics, however, its relationship with neural flexibility and regional specialization remains elusive. We identified a consciousness-related signature marked by shifting spontaneous fluctuations along a unimodal-transmodal cortical axis. This simple signature is sensitive to altered states of consciousness in single individuals, exhibiting abnormal elevation under psychedelics and in psychosis. The hierarchical dynamic reflects brain state changes in global integration and connectome diversity under task-free conditions. Quasi-periodic pattern detection revealed that hierarchical heterogeneity as spatiotemporally propagating waves linking to arousal. A similar pattern can be observed in macaque electrocorticography. Furthermore, the spatial distribution of principal cortical gradient preferentially recapitulated the genetic transcription levels of the histaminergic system and that of the functional connectome mapping of the tuberomammillary nucleus, which promotes wakefulness. Combining behavioral, neuroimaging, electrophysiological, and transcriptomic evidence, we propose that global consciousness is supported by efficient hierarchical processing constrained along a low-dimensional macroscale gradient.

Abstract Background Choosing the appropriate antipsychotic drug (APD) treatment for patients with schizophrenia (SCZ) can be challenging, as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers. Previous studies have indicated the association between treatment response and genetic and epigenetic factors, but no effective biomarkers have been identified. Hence, further research is imperative to enhance precision medicine in SCZ treatment. Methods Participants with SCZ were recruited from two randomized trials. The discovery cohort was recruited from the CAPOC trial (n = 2307) involved 6 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, Quetiapine, Aripiprazole, Ziprasidone, and Haloperidol/Perphenazine (subsequently equally assigned to one or the other) groups. The external validation cohort was recruited from the CAPEC trial (n = 1379), which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, and Aripiprazole groups. Additionally, healthy controls (n = 275) from the local community were utilized as a genetic/epigenetic reference. The genetic and epigenetic (DNA methylation) risks of SCZ were assessed using the polygenic risk score (PRS) and polymethylation score, respectively. The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis, methylation quantitative trait loci, colocalization, and promoter-anchored chromatin interaction. Machine learning was used to develop a prediction model for treatment response, which was evaluated for accuracy and clinical benefit using the area under curve (AUC) for classification, R 2 for regression, and decision curve analysis. Results Six risk genes for SCZ (LINC01795, DDHD2, SBNO1, KCNG2, SEMA7A, and RUFY1) involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response. The developed and externally validated prediction model, which incorporated clinical information, PRS, genetic risk score (GRS), and proxy methylation level (proxyDNAm), demonstrated positive benefits for a wide range of patients receiving different APDs, regardless of sex [discovery cohort: AUC = 0.874 (95% CI 0.867–0.881), R 2 = 0.478; external validation cohort: AUC = 0.851 (95% CI 0.841–0.861), R 2 = 0.507]. Conclusions This study presents a promising precision medicine approach to evaluate treatment response, which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ. Trial registration Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ ), 18. Aug 2009 retrospectively registered: CAPOC—ChiCTR-RNC-09000521 ( https://www.chictr.org.cn/showproj.aspx?proj=9014 ), CAPEC—ChiCTR-RNC-09000522 ( https://www.chictr.org.cn/showproj.aspx?proj=9013 ).

Abstract Objective The cortical representation of emotions is complex, and cortical mapping of emotional experience is incomplete. We aimed to contribute to cortical mapping of emotional experience. Methods Clinical data from 400 patients with medically refractory epilepsy who underwent stereo‐electroencephalography implantation for localization of the epileptogenic zone at the Beijing Institute of Functional Neurosurgery between October 2015 and June 2021 were collected retrospectively. Furthermore, we reviewed studies that described cortical mapping of emotional experience through electrical cortical stimulation (ECS). Affective responses similar to ictal aura and electrode contacts located in the SOZ were excluded to investigate emotional experiences in normal brain regions. Results Emotional experiences were evoked by stimulation at 10 electrode contacts in the seven patients, including five contacts that evoked mirth and excitement, one contact that evoked calmness, three contacts that evoked fear, and one contact that evoked sadness. In addition, 21 studies that evaluated emotional experiences in response to cortical electrical stimulation were reviewed. Emotions were distributed in the amygdala, hippocampus, temporal lobe, frontal lobe, insula, frontal operculum, parietal operculum, and cingulate cortex. Significance We provided additional evidence that brain regions including the amygdala, hippocampus, temporal lobe, frontal lobe, insula, frontal operculum, parietal operculum, and cingulate cortex were associated with emotional experience.

Abstract An accumulating number of studies have highlighted the importance of interpersonal neural synchronization (INS) between interlocutors in successful verbal communications. The opportunities for communication across different language contexts are rapidly expanding, thanks to the frequent interactions among people all over the world. However, whether the INS changes in different language contexts and how language choice affects the INS remain scarcely explored. The study recruited twenty pairs of participants to communicate in the first language (L1), second language (L2) and interlingual contexts. Using functional near-infrared spectroscopy (fNIRS), we examined the neural activities of interlocutors and analyzed their wavelet transform coherence to assess the INS of dyads. Results showed that as compared to the resting state, stronger INS was observed at the left inferior temporal gyrus, middle temporal gyrus, pre-motor and supplementary motor cortex, dorsolateral prefrontal cortex, and inferior frontal gyrus in L1; at the left middle temporal gyrus, superior temporal gyrus, and inferior frontal gyrus in L2; at the left inferior temporal gyrus and inferior frontal gyrus in interlingual context. Additionally, INS at the left inferior frontal gyrus was significantly stronger in L2 than in L1. These findings reveal the differences of the INS in different language contexts and confirm the importance of language choice for the INS changes.

Abstract The hepatotoxicity of regorafenib is one of the most noteworthy concerns for patients, however the mechanism is poorly understood. Hence, there is a lack of effective intervention strategies. Here, by comparing the target with sorafenib, we show that regorafenib-induced liver injury is mainly due to its nontherapeutic target Eph receptor A2 (EphA2). EphA2 deficiency attenuated liver damage and cell apoptosis under regorafenib treatment in male mice. Mechanistically, regorafenib inhibits EphA2 Ser897 phosphorylation and reduces ubiquitination of p53 by altering the intracellular localization of mouse double minute 2 (MDM2) by affecting the extracellular signal-regulated kinase (ERK)/MDM2 axis. Meanwhile, we found that schisandrin C, which can upregulate the phosphorylation of EphA2 at Ser897 also has protective effect against the toxicity in vivo. Collectively, our findings identify the inhibition of EphA2 Ser897 phosphorylation as a key cause of regorafenib-induced hepatotoxicity, and chemical activation of EphA2 Ser897 represents a potential therapeutic strategy to prevent regorafenib-induced hepatotoxicity.

Online monitoring and real-time feedback on inclusions in molten metal are essential for metal quality control. However, existing methods for detecting aluminum melt inclusions face challenges, including interference, prolonged processing times, and latency. This paper presents the design and development of an online monitoring system for molten metal inclusions. Initially, the system facilitates real-time adjustment of signal acquisition parameters through a multiplexer. Subsequently, it employs a detection algorithm capable of swiftly extracting pulse peaks, with this task integrated into our proprietary host computer software to ensure timely detection and data visualization. Ultimately, we developed a monitoring device integrated with this online monitoring system, enabling the online monitoring of the aluminum alloy filtration process. Our findings indicate that the system can accurately measure the size and concentration of inclusions during the filtration process in real time, offering enhanced detection speed and stability compared to the industrial LiMCA CM (liquid metal cleanliness analyzer continuous monitoring) standard. Furthermore, our evaluation of the filtration process demonstrates that the effectiveness of filtration significantly improves with the increase in inclusion sizes, and the synergistic effect of combining CFF (ceramic foam filter) and MCF (metallics cartridge filter) filtration methods exceeds the performance of the CFF method alone. This system thus provides valuable technical support for optimizing filtration processes and controlling inclusion quality.

Traditional methods for assessing the cleanliness of liquid metal are characterized by prolonged detection times, delays, and susceptibility to variations in sampling conditions. To address these limitations, an online cleanliness-analyzing system grounded in the method of the electrical sensing zone has been developed. This system facilitates real-time, in situ, and quantitative analysis of inclusion size and amount in liquid metal. Comprising pneumatic, embedded, and host computer modules, the system supports the continuous, online evaluation of metal cleanliness across various metallurgical processes in high-temperature environments. Tests conducted with gallium liquid at 90 °C and aluminum melt at 800 °C have validated the system’s ability to precisely and quantitatively detect inclusions in molten metal in real time. The detection procedure is stable and reliable, offering immediate data feedback that effectively captures fluctuations in inclusion amount, thereby meeting the metallurgical industry’s demand for real-time analyzing and control of inclusion cleanliness in liquid metal. Additionally, the system was used to analyze inclusion size distribution during the hot-dip galvanizing process. At a zinc melt temperature of 500 °C, it achieved a detection limit of 21 μm, simultaneously providing real-time data on the size and amount distribution of inclusions. This represents a novel strategy for the online monitoring and quality control of zinc slag throughout the hot-dip galvanizing process.

To address the most significant environmental challenges, the quest for high-performance gas sensing materials is crucial. Among numerous two-dimensional materials, this study investigates the gas-sensitive capabilities of monolayer As, Sb, and Bi materials. To compare the gas detection abilities of these three materials, we employ first-principles calculations to comprehensively study the adsorption behavior of NO and NO2 gas molecules on the material surfaces. The results indicate that monolayer Bi material exhibits reasonable adsorption distances, substantial adsorption energies, and significant charge transfer for both NO and NO2 gases. Therefore, among the materials studied, it demonstrates the best gas detection capability. Furthermore, monolayer As and Sb materials exhibit remarkably high capacities for adsorbing NO and NO2 gas molecules, firmly interacting with the gas molecules. Gas adsorption induces changes in the material’s work function, suggesting the potential application of these two materials as catalysts.

Chip-scale programmable optical signal processors are often used to flexibly manipulate the optical signals for satisfying the demands in various applications, such as lidar, radar, and artificial intelligence. Silicon photonics has unique advantages of ultra-high integration density as well as CMOS compatibility, and thus makes it possible to develop large-scale programmable optical signal processors. The challenge is the high silicon waveguides propagation losses and the high calibration complexity for all tuning elements due to the random phase errors. In this paper, we propose and demonstrate a programmable silicon photonic processor for the first time by introducing low-loss multimode photonic waveguide spirals and low-random-phase-error Mach-Zehnder switches. The present chip-scale programmable silicon photonic processor comprises a 1×4 variable power splitter based on cascaded Mach-Zehnder couplers (MZCs), four Ge/Si photodetectors, four channels of thermally-tunable optical delaylines. Each channel consists of a continuously-tuning phase shifter based on a waveguide spiral with a micro-heater and a digitally-tuning delayline realized with cascaded waveguide-spiral delaylines and MZSs for 5.68 ps time-delay step. Particularly, these waveguide spirals used here are designed to be as wide as 2 µm, enabling an ultralow propagation loss of 0.28 dB/cm. Meanwhile, these MZCs and MZSs are designed with 2-µm-wide arm waveguides, and thus the random phase errors in the MZC/MZS arms are negligible, in which case the calibration for these MZSs/MZCs becomes easy and furthermore the power consumption for compensating the phase errors can be reduced greatly. Finally, this programmable silicon photonic processor is demonstrated successfully to verify a number of distinctively different functionalities, including tunable time-delay, microwave photonic beamforming, arbitrary optical signal filtering, and arbitrary waveform generation.

Polymer-derived ultra-high-temperature ceramic (UHTC) nanocomposites have attracted growing attention due to the increasing demands for advanced thermal structure components in aerospace. Herein, hafnium carbide (HfC) whiskers are successfully fabricated in carbon fiber preforms via the polymer-derived ceramic (PDC) method. A novel carbon nanotube (CNT) template growth mechanism combined with the PDC method is proposed in this work, which is different from the conventional vapor–liquid–solid (VLS) mechanism that is commonly used for polymer-derived nanostructured ceramics. The CNTs are synthesized and proved to be the templates for fabricating the HfC whiskers, which are generated by the released low-molecular-weight gas such as CO, CO2, and CH4 during the pyrolysis of a Hf-containing precursor. The formed products are composed of inner single crystal HfC whiskers that are measured to be several tens of micrometers in length and 100–200 nm in diameter and outer HfC/HfO2 particles. Our work not only proposes a new strategy to prepare the HfC whiskers, but also puts forward a new thinking of the efficient utilization of a UHTC polymer precursor.

A hyperspectral image (HSI) has also highly correlated and redundant data, in addition to abundant spatial and spectral information. Only the spectral characteristics were usually utilized to perform the HSI classification in most previous studies, which leads to unsatisfactory accuracy and precision. The combination of Principal Component Analysis (PCA), Local Binary Pattern (LBP) and Back Propagation Neural Network (BPNN) (PCA-LBP-BPNN) was used to propose a novel classification method. More specifically, PCA was first used to reduce the dimensionality of HSIs for obtaining independent spectral bands sensitive to the classified objects. LBP was then adopted to extract the spatial texture features. Finally, the feature vectors were formed by fusing spatial–spectral features and input into BPNN for HSI classification. Three key parameters including the number of principal components (p) and the neurons in the hidden layer (l) as well as the learning rate (r) were optimally selected to improve the classification accuracy. Three publicly available hyperspectral datasets including Pavia University (PU), Salinas (Sa) and Botswana (Bo) were selected to validate the performance by comparing the kNN (k-Nearest Neighbor), SVM (Support Vector Machine) and Contextual Deep Convolutional Neural Network (CDCNN). The overall accuracy of PCA-LBP-BPNN reached 93.67%, 98.09% and 92.97%, respectively, for the three datasets. The method had a satisfying performance than kNN, SVM and CDCNN for the PU and Sa, but it had lower accuracies than kNN and CDCNN for the Bo due to extremely similar spectral responses. PCA-LBP-BPNN generally has satisfactory practicability and robustness in adapting to different hyperspectral datasets.

Background Neurogenic bladder (NB) following suprasacral spinal cord injury (SSCI) is an interstitial disease with the structural remodeling of bladder tissue and matrix over-deposition. Circular RNAs (circRNAs) are involved in fibrotic disease development through their post-transcriptional regulatory functions. This study aimed to use transcriptome high-throughput sequencing to investigate the process of NB and bladder fibrosis after SSCI. Methods Spinal cord transection at the T10–T11 level was used to construct the SSCI model in rats (10–week–old female Wistar rats, weighing 200 ± 20 g). The bladders were collected without (sham group) and with (SSCI 1–3 groups) NB status. Morphological examination was conducted to assess the extent of bladder fibrosis. Additionally, RNA sequencing was utilized to determine mRNAs and circRNAs expression patterns. The dynamic changes of differentially expressed mRNAs (DEMs) and circRNAs (DECs) in different periods of SSCI were further analyzed. Results Bladder weight, smooth muscle cell hypertrophy, and extracellular matrix gradually increased after SSCI. Compared with the sham group, 3,255 DEMs and 1,339 DECs, 3,449 DEMs and 1,324 DECs, 884 DEMs, and 1,151 DECs were detected in the SSCI 1–3 groups, respectively. Specifically, circRNA3621, circRNA0617, circRNA0586, and circRNA4426 were significant DECs common to SSCI 1–3 groups compared with the sham group. Moreover, Gene Ontology (GO) enrichment suggested that inflammatory and chronic inflammatory responses were the key events in NB progression following SSCI. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment associated with the “Chemokine signaling pathway”, the “IL-17 signaling pathway”, and the “TGF-beta signaling pathway” suggests their potential involvement in regulating biological processes. The circRNA–miRNA–mRNA interaction networks of DECs revealed rno-circ-2239 (micu2) as the largest node, indicating that the rno-circ-2239–miRNA–mRNA–mediated network may play a critical role in the pathogenesis of SSCI-induced NB. Conclusions This study offers a comprehensive outlook on the possible roles of DEMs and DECs in bladder fibrosis and NB progression following SSCI. These findings have the potential to serve as novel biomarkers and therapeutic targets.

Abstract Nephrotoxicity has become prominent due to the increase in the clinical use of nilotinib, a second‐generation BCR‐ABL1 inhibitor in the first‐line treatment of Philadelphia chromosome‐positive chronic myeloid leukemia. To date, the mechanism of nilotinib nephrotoxicity is still unknown, leading to a lack of clinical intervention strategies. Here, it is found that nilotinib could induce glomerular atrophy, renal tubular degeneration, and kidney fibrosis in an animal model. Mechanistically, nilotinib induces intrinsic apoptosis by specifically reducing the level of BCL2 like 1 (Bcl‐XL) in both vascular endothelial cells and renal tubular epithelial cells, as well as in vivo. It is confirmed that chloroquine (CQ) intervenes with nilotinib‐induced apoptosis and improves mitochondrial integrity, reactive oxygen species accumulation, and DNA damage by reversing the decreased Bcl‐XL. The intervention effect is dependent on the alleviation of the nilotinib‐induced reduction in ubiquitin specific peptidase 13 (USP13) and does not rely on autophagy inhibition. Additionally, it is found that USP13 abrogates cell apoptosis by preventing excessive ubiquitin‒proteasome degradation of Bcl‐XL. In conclusion, the research reveals the molecular mechanism of nilotinib's nephrotoxicity, highlighting USP13 as an important regulator of Bcl‐XL stability in determining cell fate, and provides CQ analogs as a clinical intervention strategy for nilotinib's nephrotoxicity.

Summary: Large biosynthetic gene cluster (BGC) cloning is important for discovering natural product-based drugs and remains challenging in high GC content microorganisms (e.g., Actinobacteria). Here, we present an in vitro CRISPR-Cas12a-mediated protocol for direct cloning of large DNA fragments. We describe steps for crRNA design and preparation, genomic DNA isolation, and CRISPR-Cas12a cleavage and capture plasmid construction and linearization. We then detail target BGC and plasmid DNA ligation and transformation and screening for positive clones.For complete details on the use and execution of this protocol, please refer to Liang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Social networks are becoming increasingly popular and significant. One of the most distinctive features of these networks is their dynamic nature, which means that they change over time. Consequently, the community structure on these platforms also changes with time, making the detection of community structure a crucial area of research. Specifically, there is still a lack of understanding of how social networks and communities evolve over time. In this paper, we reveal that individual changing topics (i.e., individual temporal semantics) are a vital factor that drives community evolution. A novel dynamic community detection model is proposed, which takes into account natural evolutionary features. The model first partitions social networks into snapshots. It then detects the community structure at each snapshot by utilizing individual changing topics and information from the previous snapshot. Finally, the evolution of users’ interested topic distributions and topic distributions of communities are identified. The model is compared with five state-of-the-art baselines on two real datasets, and the experimental results demonstrate that our model outperforms all baselines.

Speech Emotion Recognition (SER) is a common aspect of human-computer interaction and has significant applications in fields such as healthcare, education, and elder care. Although researchers have made progress in speech emotion feature extraction and model identification, they have struggled to create an SER system with satisfactory recognition accuracy. To address this issue, we proposed a novel algorithm called F-Emotion to select speech emotion features and established a parallel deep learning model to recognize different types of emotions. We first extracted the emotion features from speech and calculated the F-Emotion value for each feature. These values were then used to determine the combination of speech emotion features that was optimal for speech emotion recognition. Next, a parallel deep learning model was established with the speech emotion feature combination as input to train and test for each type of emotion. Finally, decision fusion was applied to the parallel output results to obtain an overall recognition result. These analyses were conducted on two datasets, RAVDESS and EMO-DB, with the accuracy of speech emotion recognition reaching 82.3% and 88.8%, respectively. The results demonstrate that the F-Emotion algorithm can effectively analyze the correspondence between speech emotion features and emotion types. The MFCC feature best describes emotions of neutrality, happiness, fear, and surprise, and Mel best describes emotions of anger and sadness. The parallel deep learning model mechanism can improve the accuracy of speech emotion recognition.