Effects of four antibiotics on the photosynthetic light reactions in the green alga Chlorella pyrenoidosa.

Antibiotics are ubiquitously present in aquatic environments, posing a serious ecological risk to aquatic ecosystems. However, the effects of antibiotics on the photosynthetic light reactions of freshwater algae and the underlying mechanisms are relatively less understood. In this study, the effects of 4 representative antibiotics (clarithromycin, enrofloxacin, tetracycline, and sulfamethazine) on a freshwater alga (Chlorella pyrenoidosa) and the associated mechanisms, primarily focusing on key regulators of the photosynthetic light reactions, were evaluated. Algae were exposed to different concentrations of clarithromycin (0.0-0.3 mg/L), enrofloxacin (0.0-30.0 mg/L), tetracycline (0.0-10.0 mg/L), and sulfamethazine (0.0-50.0 mg/L) for 7 days. The results showed that the 4 antibiotics inhibited the growth, the photosynthetic pigment contents, and the activity of antioxidant enzymes. In addition, exposure to clarithromycin caused a 118.4 % increase in malondialdehyde (MDA) levels at 0.3 mg/L. Furthermore, the transcripts of genes for the adenosine triphosphate (ATP) - dependent chloroplast proteases (ftsH and clpP), genes in photosystem II (psbA, psbB, and psbC), genes related to ATP synthase (atpA, atpB, and atpH), and petA (related to cytochrome b6/f complex) were altered by clarithromycin. This study contributes to a better understanding of the risk of antibiotics on primary producers in aquatic environment.

Selection Signal Analysis Reveals Hainan Yellow Cattle Are Being Selectively Bred for Heat Tolerance.

Hainan yellow cattle are indigenous Zebu cattle from southern China known for their tolerance of heat and strong resistance to disease. Generations of adaptation to the tropical environment of southern China and decades of artificial breeding have left identifiable selection signals in their genomic makeup. However, information on the selection signatures of Hainan yellow cattle is scarce. Herein, we compared the genomes of Hainan yellow cattle with those of Zebu, Qinchuan, Nanyang, and Yanbian cattle breeds by the composite likelihood ratio method (CLR), Tajima's D method, and identifying runs of homozygosity (ROHs), each of which may provide evidence of the genes responsible for heat tolerance in Hainan yellow cattle. The results showed that 5210, 1972, and 1290 single nucleotide polymorphisms (SNPs) were screened by the CLR method, Tajima's D method, and ROH method, respectively. A total of 453, 450, and 325 genes, respectively, were identified near these SNPs. These genes were significantly enriched in 65 Gene Ontology (GO) functional terms and 11 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (corrected p < 0.05). Five genes-Adenosylhomocysteinase-like 2, DnaJ heat shock protein family (Hsp40) member C3, heat shock protein family A (Hsp70) member 1A, CD53 molecule, and zinc finger and BTB domain containing 12-were recognized as candidate genes associated with heat tolerance. After further functional verification of these genes, the research results may benefit the understanding of the genetic mechanism of the heat tolerance in Hainan yellow cattle, which lay the foundation for subsequent studies on heat stress in this breed.

Ultralow-loss optical interconnect enabled by topological unidirectional guided resonance.

Grating couplers that interconnect photonic chips to off-chip components are crucial for various optoelectronics applications. Despite numerous efforts in past decades, the existing grating couplers are still far from optimal in energy efficiency and thus hinder photonic integration toward a larger scale. Here, we propose a strategy to achieve ultralow-loss grating couplers by using unidirectional guided resonances (UGRs), suppressing the useless downward radiation with no mirror on the bottom. By engineering the dispersion and apodizing the geometry of grating, we experimentally realize a grating coupler with a record-low loss of -0.34 dB and 1-dB bandwidth exceeding 30 nm at the telecom wavelength of 1550 nm and further demonstrate an optic via with a loss of only -0.94 dB. Given that UGRs ubiquitously exist in a variety of grating geometries, our work sheds light on a systematic method to achieve energy-efficient optical interconnect and paves the way to large-scale photonic integration.

Multifunctional cardiac microphysiological system based on transparent ITO electrodes for simultaneous optical measurement and electrical signal monitoring.

Drug-induced cardiotoxicity is a significant contributor to drug recalls, primarily attributed to limitations in existing drug screening platforms. Traditional heart-on-a-chip platforms often employ metallic electrodes to record cardiomyocyte electrical signals. However, this approach hinders direct cardiomyocyte morphology observation and typically yields limited functionality. Consequently, this limitation may lead to an incomplete understanding of cardiomyocyte characteristics. To address these challenges, we introduce a multifunctional cardiac microphysiological system featuring transparent indium tin oxide electrodes. This innovative design aims to overcome the limitations of conventional heart-on-a-chip systems where metal electrodes interfere with the observation of cells and increase the difficulty of subsequent image processing of cell images. In addition to facilitating optical measurement combined with image processing capabilities, this system integrates a range of electrodes with diverse functionalities. These electrodes can realize cellular electrical stimulation, field potential monitoring, and impedance change tracking, enabling a comprehensive investigation of various cardiomyocyte traits. To demonstrate its versatility, we investigate the effects of four cardiac drugs with distinct pharmacological profiles on cardiomyocytes using this system. This platform provides a means for quantitatively and predictively assessing cardiac toxicity, which could be applied to conduct a comprehensive evaluation during the drug discovery process.

Predicting Dysphonia by Measuring Surface Electromyographic Activity of the Supralaryngeal Muscles.

PURPOSE: This study set out to investigate whether individuals with dysphonia, as determined by either self-assessment or clinician-based auditory-perceptual judgment, exhibited differences in perilaryngeal muscle activities using surface electromyography (sEMG) during various phonatory tasks. Additionally, the study aimed to assess the effectiveness of sEMG in identifying dysphonic cases. METHOD: A total of 77 adults (44 women, 33 men, Mage = 30.4 years) participated in this study, with dysphonic cases identified separately using either a 10-item Voice Handicap Index (VHI-10) or clinician-based auditory-perceptual voice quality (APVQ) evaluation. sEMG activities were measured from the areas of suprahyoid and sternocleidomastoid muscles during prolonged vowel /i/ phonations at different pitch and loudness levels. Normalized root-mean-square value against the maximal voluntary contraction (RMS %MVC) of the sEMG signals was obtained for each phonation and compared between subject groups and across phonatory tasks. Additionally, binary logistic regression analysis was performed to determine how the sEMG measures could predict the VHI-10-based or APVQ-based dysphonic cases. RESULTS: Participants who scored above the criteria on either the VHI-10 (n = 29) or APVQ judgment (n = 17) exhibited significantly higher RMS %MVC in the right suprahyoid muscles compared to the corresponding control groups. Although the RMS %MVC value from the right suprahyoid muscles alone was not a significant predictor of self-evaluated dysphonic cases, a combination of the RMS %MVC values from both the right and left suprahyoid muscles significantly predicted APVQ-based dysphonic cases with a 69.66% fair level. CONCLUSIONS: This study found that individuals with dysphonia, as determined by either self-assessment or APVQ judgment, displayed more imbalanced suprahyoid muscle activities in voice production compared to nondysphonic groups. The combination of the sEMG measures from both left and right suprahyoid muscles showed potential as a predictor of dysphonia with a fair level of confidence. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25112804.

Engineered M2 macrophage-derived extracellular vesicles with platelet membrane fusion for targeted therapy of atherosclerosis.

Atherosclerosis is featured as chronic low-grade inflammation in the arteries, which leads to the formation of plaques rich in lipids. M2 macrophage-derived extracellular vesicles (M2EV) have significant potential for anti-atherosclerotic therapy. However, their therapeutic effectiveness has been hindered by their limited targeting capability in vivo. The objective of this study was to create the P-M2EV (platelet membrane-modified M2EV) using the membrane fusion technique in order to imitate the interaction between platelets and macrophages. P-M2EV exhibited excellent physicochemical properties, and microRNA (miRNA)-sequencing revealed that the extrusion process had no detrimental effects on miRNAs carried by the nanocarriers. Remarkably, miR-99a-5p was identified as the miRNA with the highest expression level, which targeted the mRNA of Homeobox A1 (HOXA1) and effectively suppressed the formation of foam cells in vitro. In an atherosclerotic low-density lipoprotein receptor-deficient (Ldlr-/-) mouse model, the intravenous injection of P-M2EV showed enhanced targeting and greater infiltration into atherosclerotic plaques compared to regular extracellular vesicles. Crucially, P-M2EV successfully suppressed the progression of atherosclerosis without causing systemic toxicity. The findings demonstrated a biomimetic platelet-mimic system that holds great promise for the treatment of atherosclerosis in clinical settings.

Research on the characteristics and influencing factors of the spatial correlation network of cultivated land utilization ecological efficiency in the upper reaches of the Yangtze River, China.

Researching the structural characteristics of the spatial correlation network of cultivated land utilization ecological efficiency is of great significance to China's food security and agricultural green and low-carbon development. Taking 47 cities (autonomous prefectures) in the upper reaches of the Yangtze River as the research object, the ecological efficiency of cultivated land utilization from 2010 to 2020 was measured based on the unexpected output model (Super SBM), and the spatial correlation matrix was constructed using the revised gravity model. The structural characteristics of the spatial correlation network were analyzed using the social network model (SNA), and finally, the factors affecting the spatial correlation network of cultivated land utilization ecological efficiency in the upper reaches of the Yangtze River were analyzed through the quadratic assignment procedure (QAP) model. The results show that: (1) the ecological efficiency of cultivated land utilization in the upper reaches of the Yangtze River has been increasing year by year, but the overall level is low, and there is a large gap among provinces. Sichuan Province has the highest average value of 0.605, and Yunnan Province has the lowest average value of 0.359. (2) The ecological efficiency of cultivated land utilization in the upper reaches of the Yangtze River has broken through the provincial boundaries and has formed an obvious spatial correlation network, but the overall density is low, and the network is still relatively loose, needing further development and improvement. Chengdu, Yibin, Luzhou, and other cities are located in the center of the network and have formed four cohesive subgroups. (3)The differences in the level of agricultural economic development, the rural per capita disposable income, the differences in agricultural mechanization intensity, the regional population differences, and spatial adjacency have an impact on the spatial network of ecological efficiency of cultivated land utilization in the upper reaches of the Yangtze River. The difference in the level of agricultural economic development, the rural per capita disposable income, and the differences in agricultural mechanization intensity are negatively correlated, while the regional population differences are positively correlated with spatial adjacency.

Detection of Runs of Homozygosity and Identification of Candidate Genes in the Whole Genome of Tunchang Pigs.

Tunchang pigs are an indigenous pig population in China known for their high tolerance to roughage, delicious meat, and fecundity. However, the number of Tunchang pigs has been declining due to the influence of commercial breeds and African swine fever, which could potentially lead to inbreeding. To assess the inbreeding level and the genetic basis of important traits in Tunchang pigs, our research investigated the patterns in "runs of homozygosity" (ROHs) using whole genome resequencing data from 32 Tunchang pigs. The study aimed to determine the length, number, coverage, and distribution model of ROHs in Tunchang pigs, as well as genomic regions with high ROH frequencies. The results of the study revealed that a total of 20,499,374 single-nucleotide polymorphisms (SNPs) and 1953 ROH fragments were recognized in 32 individuals. The ROH fragments in Tunchang pigs were predominantly short, ranging from 0.5 to 1 megabases (Mb) in length. Furthermore, the coverage of ROHs varied across chromosomes, with chromosome 3 having the highest coverage and chromosome 11 having the lowest coverage. The genetic diversity of Tunchang pigs was found to be relatively high based on the values of HE (expected heterozygosity), HO (observed heterozygosity), pi (nucleotide diversity), Ne (effective population size), and MAF (minor allele frequency). The average inbreeding coefficients of Tunchang pigs, as determined by three different methods (FHOM, FGRM, and FROH), were 0.019, 0.0138, and 0.0304, respectively. These values indicate that the level of inbreeding in Tunchang pigs is currently low. Additionally, the study identified a total of 13 ROH islands on all chromosomes, which in total contained 38,913 SNPs and 120 genes. These ROH islands included genes associated with economically important traits, including meat quality (GYS1, PHLPP1, SLC27A5, and CRTC1), growth and development (ANKS1A, TAF11, SPDEF, LHB, and PACSIN1), and environmental adaptation (SLC26A7). The findings of this research offer valuable perspectives on the present status of Tunchang pig resources and offer a reference for breeding conservation plans and the efficient utilization of Tunchang pigs in the future. By understanding the inbreeding level and genetic basis of important traits in Tunchang pigs, conservation efforts can be targeted towards maintaining genetic diversity and promoting the sustainable development of this indigenous pig population.

Characteristics of gut microbiota and metabolomic of Hainan Tunchang pigs at various growth stages.

Numerous gut microorganisms residing in the gut tract and their metabolites play an important role in animal growth. Diet, as the main factor, affects the changes of gut microbiota, and host genetics also have a significant impact on gut microbiota, including growth stages. However, the differences of gut microbiota and its metabolites at various growth stages in local pig breed remains unclear. We used 16S rRNA gene sequencing and untargeted metabolomics to investigate the fecal microbiota and metabolites in different developmental stages of Hainan Tunchang pigs. The relative proportions of dominant bacteria Firmicutes and Spirochaetes increased, Bacteroidetes and Proteobacteria decreased with the development. As age increased, different physiological states led to structural and functional changes in animal nutrition metabolism and immune needs, as well as changes in gut microbiota and its metabolites. We have detected several statistically different microbial and metabolic biomarkers at different growth stages. Meanwhile, through correlation analysis between differential bacteria and metabolites, it was found that the bacteria forming networks with their significant related metabolites were different at various growth stages, Holdemanella, Sharpea, Subdoligranulum, and uncultured_bacterium_o_Bacteroidales were enriched between preweaning piglets and weaning piglets, and they all positive correlated with related metabolites. We also found that the differential bacteria were significantly related to short-chain fatty acid. These findings might provide new insights into the developmental changes of gut microbiota in local pig breeds and the interaction mechanism between the body, and improve pig growth performance and efficiency by regulating the composition of gut microbiota and metabolites.

Exploring potential causal associations between autoimmune diseases and colorectal cancer using bidirectional Mendelian randomization.

Several observational studies have revealed an association between autoimmune diseases (AIDs) and colorectal cancer (CRC), although their causal association remained controversial. Therefore, our study used a two-sample Mendelian randomization (MR) analysis to verify the causal association between AIDs and CRC. We employed three common MR approaches, including inverse variance weighted (IVW), weighted median, and MR-Egger methods, to assess the causal association between type 1 diabetes (T1D), systemic lupus erythematosus, rheumatoid arthritis, psoriasis, multiple sclerosis, juvenile idiopathic arthritis, celiac disease, and primary sclerosing cholangitis (PSC) and CRC. The reverse MR analysis was performed to assess the possibility of reverse causation. To evaluate the validity of the analysis, we also performed sensitivity analysis, such as the heterogeneity test, the horizontal pleiotropy test, and the leave-one-out sensitivity analysis, and validated the results in the validation cohort. Our results showed that genetically predicted T1D was nominally associated with a lower risk of CRC (IVW OR = 0.965, 95% CI = 0.939-0.992, P = 0.012). However, genetic susceptibility to psoriasis nominally increased the risk of CRC (IVW OR = 1.026, 95% CI = 1.002-1.050, P = 0.037). Genetically predicted PSC had a significant causal effect on the increasing risk of CRC (IVW OR = 1.038, 95% CI = 1.016-1.060, P = 5.85 × 10-4). Furthermore, the MR analysis between PSC and the CRC validation cohort indicated consistent results. We found no causal association between genetically predicted other five AIDs and CRC (P > 0.05). The results of reverse MR analysis showed that genetically predicted CRC had no causal effect on T1D, psoriasis, and PSC (P > 0.05). The sensitivity analysis demonstrated that the results of the MR analysis were reliable. Our findings help to understand the causal association between AIDs and CRC, which deserves further investigation.

Nanographene with a Nitrogen-Doped Cavity.

Nitrogen-doped cavities are pervasive in graphenic materials, and represent key sites for catalytic and electrochemical activity. However, their structures are generally heterogeneous. In this study, we present the synthesis of a well-defined molecular cutout of graphene featuring N-doped cavity. The graphitization of a macrocyclic pyridinic precursor was achieved through photochemical cyclodehydrochlorination. In comparison to its counterpart with pyridinic nitrogen at the edges, the pyridinic nitrogen atoms in this nanographene cavity exhibit significantly reduced basicity and selective binding to Ag+ ion. Analysis of the protonation and coordination equilibria revealed that the tri-N-doped cavity binds three protons, but only one Ag+ ion. These distinct protonation and coordination behaviors clearly illustrate the space confinement effect imparted by the cavities.

Multi-level magnetic microrobot delivery strategy within a hierarchical vascularized organ-on-a-chip.

Targeted microrobotic delivery within the circulatory system holds significant potential for medical theranostic applications. Existing delivery strategies of microrobots encounter challenges such as slow speed, limited navigation control, and dispersal under dynamic flow conditions. Furthermore, within the realm of microrobots, in vitro testing platforms often lack essential biological microenvironments, while in vivo studies conducted on animal models are constrained by limited detection resolution. In this study, we propose a multi-level magnetic delivery strategy that integrates a tethered microrobotic guidewire and untethered swimming microrobots. The amalgamation compensates for their inherent constraints, ensuring a robust and highly efficient delivery of microrobots under complex physiological conditions over extensive distances. Concurrently, a hierarchical vascular network encompassing engineered arteries/veins and capillary networks was constructed by integrating vasculogenesis and endothelial cell (EC) lining strategies, thereby providing an in vivo-like testing platform for microrobots. Experimental evidence demonstrates that the flexible microrobotic guidewire can be precisely directed to any entrance of the second-tier branches, with its inner lumen providing an "express lane" for rapid passage of microrobots through complex fluidic environments without direct contact. After release, dynamically assembled swarms could effectively locomote on the micro-topography of the EC-lined channel surface without becoming trapped and congregate within specified regions inside capillary lumens when guided collectively by a biologically safe magnetic field. Additionally, the superparamagnetic capabilities of microrobotic swarms ensure their dissolution into monodispersed entities upon withdrawal of the magnetic field, mitigating the risk of intravascular thrombosis. The hierarchical vascularized organ-on-a-chip platform establishes a comprehensive testing platform that integrates imaging, control, and a functional 3D microvascular environment, thereby enhancing its suitability for microrobotic applications encompassing targeted drug delivery, thrombus ablation, sensing and diagnosis, etc.

High Catalytic Activity of Co-centered 2D Metal Organic Frameworks toward Bifunctional Oxygen Evolution and Reduction Reactions: Rationalized by Spin Polarization Effect.

CoX4 (X = NH, S, and O) motifs have demonstrated their high catalytic activity in the platforms of metal organic frameworks (MOFs), however, the underlying reason is still unrevealed. Herein, we propose monolayers constructed by linking TMNxO4-x motifs (TM = Fe, Co, Ni, Cu) with trioxotriangulenes (TOTs) as suitable models to clarify the structure-property-performance relationship of 2D MOFs for the oxygen evolution/reduction reaction (OER/ORR). The highly robust catalytic activity of CoNxO4-x for both the OER and the ORR has been confirmed, even surpassing that of most previously reported 2D MOFs and SACs. This activity is attributed to the moderate interaction between Co and the key intermediate species, which can be modulated by the coordinating atoms. We reveal spin momentum as a reliable activity descriptor in rationalizing the OER/ORR activity, which can be extended to many other 2D MOFs. The elucidated structure-activity relationship is significant for the development of effective bifunctional OER/ORR electrocatalysts.

Effectiveness and safety analysis of titanium mesh grafting versus bone grafting in the treatment of spinal Tuberculosis: a systematic review and meta-analysis.

BACKGROUND: To systematically assess the safety and effectiveness of titanium mesh grafting compared with bone grafting in the treatment of spinal tuberculosis. METHODS: Electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library, were searched from their inception until April 2023. The outcome indicators for patients treated with titanium mesh grafting or bone grafting for spinal tuberculosis include surgical duration, intraoperative blood loss, graft fusion time, American Spinal Injury Association (ASIA) Spinal Cord Injury Grade E assessment, VAS score, lumbar pain score, post-graft kyphotic angle, and postoperative complications. The Newcastle-Ottawa Scale (NOS) and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach were used for quality assessment and evidence grading of clinical studies. Funnel plots and Begg's test were employed for bias assessment. RESULTS: A total of 8 studies were finally included, comprising 523 patients, with 267 cases of titanium mesh fixation and 256 cases of bone grafting. The meta-analysis showed no significant statistical differences in surgical duration (Weighted Mean Difference (WMD) = -7.20, 95% Confidence Interval (CI): -28.06 to 13.67, P = 0.499), intraoperative blood loss (WMD = 16.22, 95% CI: -40.62 to 73.06, P = 0.576), graft fusion time (WMD = 0.97, 95% CI: -0.88 to 2.81, P = 0.304), ASIA Spinal Cord Injury Grade E assessment (Relative Risk (RR) = 1.03, 95% CI: 0.97 to 1.09, P = 0.346), and overall complications (RR = 0.87, 95% CI: 0.49 to 1.55, P = 0.643). Differences in VAS score, ODI lumbar pain score, and post-graft kyphotic angle between the titanium mesh grafting group and the bone grafting group were not significant within the 95% CI range. The rate of postoperative implant subsidence was slightly lower in bone grafting than in titanium mesh grafting (RR = 9.30, 95% CI: 1.05 to 82.22, P = 0.045). CONCLUSIONS: Both bone grafting and titanium mesh grafting are effective and safe for the surgery, with no significant statistical differences in the results. Considering the limitations of the present study, large-scale randomized controlled trials are warranted to further verify the reliability of this finding.

Genome-Wide Re-Sequencing Data Reveals the Population Structure and Selection Signatures of Tunchang Pigs in China.

Tunchang pig is one population of Hainan pig in the Hainan Province of China, with the characteristics of delicious meat, strong adaptability, and high resistance to diseases. To explore the genetic diversity and population structure of Tunchang pigs and uncover their germplasm characteristics, 10 unrelated Tunchang pigs were re-sequenced using the Illumina NovaSeq 150 bp paired-end platform with an average depth of 10×. Sequencing data from 36 individuals of 7 other pig breeds (including 4 local Chinese pig breeds (5 Jinhua, 5 Meishan, 5 Rongchang, and 6 Wuzhishan), and 3 commonly used commercial pig breeds (5 Duorc, 5 Landrace, and 5 Large White)) were downloaded from the NCBI public database. After analysis of genetic diversity and population structure, it has been found that compared to commercial pigs, Tunchang pigs have higher genetic diversity and are genetically close to native Chinese breeds. Three methods, FST, θπ, and XP-EHH, were used to detect selection signals for three breeds of pigs: Tunchang, Duroc, and Landrace. A total of 2117 significantly selected regions and 201 candidate genes were screened. Gene enrichment analysis showed that candidate genes were mainly associated with good adaptability, disease resistance, and lipid metabolism traits. Finally, further screening was conducted to identify potential candidate genes related to phenotypic traits, including meat quality (SELENOV, CBR4, TNNT1, TNNT3, VPS13A, PLD3, SRFBP1, and SSPN), immune regulation (CD48, FBL, PTPRH, GNA14, LOX, SLAMF6, CALCOCO1, IRGC, and ZNF667), growth and development (SYT5, PRX, PPP1R12C, and SMG9), reproduction (LGALS13 and EPG5), vision (SLC9A8 and KCNV2), energy metabolism (ATP5G2), cell migration (EPS8L1), and olfaction (GRK3). In summary, our research results provide a genomic overview of the genetic variation, genetic diversity, and population structure of the Tunchang pig population, which will be valuable for breeding and conservation of Tunchang pigs in the future.

Reconstruction of complicated spinal tuberculosis with long-segment fibula transplantation: a case report.

BACKGROUND: Treating complex cases of spinal tuberculosis (STB) that involve multiple vertebral bodies and cause destruction of the spinal structure, kyphotic deformity, and acute nerve injury can be challenging. This report describes the course of treatment and 5-year follow-up of a complex case of multisegmental STB. CASE PRESENTATION: This report describes a case of tuberculosis affecting the vertebrae extending from thoracic 12 to lumbar 5 in a 60-year-old woman who suffered sudden paralysis in both lower extremities. The patient underwent emergency posterior paraspinal abscess clearance, laminectomy with spinal decompression. Partial correction of the kyphotic deformity via long-segment fixation from the T9 vertebral body to the ilium in a one-stage posterior procedure. The patient's neurological status was diagnosed as grade E on the American Spinal Injury Association (ASIA) scale after the one-stage operation. Following standardized 4-combination anti-tuberculosis drug therapy for three months in postoperative patients, the patient underwent two-stage transabdominal anterior abscess removal, partial debridement of the lesion and bilateral fibula graft support. One year after the two-stage operation, the patient's visual analog scale (VAS) score of back pain was 1 point, and the patient's erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels returned to normal. Five years after the second-stage operation, the Oswestry disability index (ODI) of patient quality of life was 14 points. There was a 4-degree change in the Cobb angle over five years. During the five-year follow-up period, the grafted fibula did not experience any subsidence. CONCLUSION: For patients with spinal tuberculosis and acute paralysis, it is essential to relieve spinal cord compression as soon as possible to recover spinal cord function. For lesions that cannot be debrided entirely, although limited debridement combined with anti-tuberculosis drug therapy has the risk of sinus formation and tuberculosis recurrence, it is much safer than the risk of thorough debridement surgery. In this case, an unconventional long-segment fibula graft, pelvis-vertebral support, was an effective reconstruction method.

Slow-light silicon modulator with 110-GHz bandwidth.

Silicon modulators are key components to support the dense integration of electro-optic functional elements for various applications. Despite numerous advances in promoting the modulation speed, a bandwidth ceiling emerges in practices and becomes an obstacle toward Tbps-level throughput on a single chip. Here, we demonstrate a compact pure silicon modulator that shatters present bandwidth ceiling to 110 gigahertz. The proposed modulator is built on a cascade corrugated waveguide architecture, which gives rise to a slow-light effect. By comprehensively balancing a series of merits, the modulators can benefit from the slow light for better efficiency and compact size while remaining sufficiently high bandwidth. Consequently, we realize a 110-gigahertz modulator with 124-micrometer length, enabling 112 gigabits per second on-off keying operation. Our work proves that silicon modulators with 110 gigahertz are feasible, thus shedding light on its potentials in ultrahigh bandwidth applications such as optical interconnection and photonic machine learning.

CircXRN2 suppresses tumor progression driven by histone lactylation through activating the Hippo pathway in human bladder cancer.

BACKGROUND: Bladder cancer (BCa) is the fourth most common malignant tumor with a poor prognosis worldwide. Further exploration and research are needed to unmask the underlying roles and molecular mechanisms of circular RNAs. In the current study, our findings showed that circXRN2 suppresses tumor progression driven by histone lactylation by activating the Hippo pathway in human bladder cancer. METHODS: RNA immunoprecipitation (RIP) followed by circRNA sequencing confirmed circXRN2 as the research object. Overexpression of circXRN2 and knockdown of TAZ/YAP further verified the biological functions in T24 and TCCSUP cells. RIP, immunoprecipitation and coimmunoprecipitation were used to elucidate the interaction between circXRN2 and LATS1. A Seahorse metabolic analyzer was used to determine the glycolytic rate. Cleavage under targets and Tagmentation (CUT&Tag) and chromatin immunoprecipitation (ChIP) were employed to ensure the regulatory roles of H3K18 lactylation in the transcriptional activity of LCN2. RESULTS: CircXRN2 is aberrantly downregulated in bladder cancer tissues and cell lines. CircXRN2 inhibits the proliferation and migration of tumor cells both in vitro and in vivo. In addition, circXRN2 serves as a negative regulator of glycolysis and lactate production. Mechanistically, circXRN2 prevents LATS1 from SPOP-mediated degradation by binding to the SPOP degron and then activates the Hippo signaling pathway to exert various biological functions. The circXRN2-Hippo pathway regulatory axis further modulates tumor progression by inhibiting H3K18 lactylation and LCN2 expression in human bladder cancer. CONCLUSIONS: CircXRN2 suppresses tumor progression driven by H3K18 lactylation by activating the Hippo signaling pathway in human bladder cancer. Our results indicated novel therapeutic targets and provided promising strategies for clinical intervention in human bladder cancer.

Molecular action mechanisms of two novel and selective calcium release-activated calcium channel antagonists.

The prototypical calcium release-activated calcium (CRAC) channel, composed of STIM1 and Orai1, is a sought-after drug target for treating autoimmune disorders. Herein, we identified two novel and selective CRAC channel inhibitors, the indole-like compound C63368 and pyrazole core-containing compound C79413, potently and reversibly inhibiting the CRAC channel with low micromolar IC50s and sparing various off-target ion channels. These two compounds did not inhibit STIM1 activation or its coupling with Orai1, nor did they affect the channel's calcium-dependent fast inactivation. Instead, they directly acted on the Orai1 protein, with the channel's pore geometry profoundly affecting their potencies. In vitro, C63368 and C79413 effectively inhibited Jurkat cell proliferation and cytokines production in human T lymphocytes. Intragastric administration of C63368 and C79413 to mice yielded great therapeutic benefits in psoriasis and colitis animal models of autoimmune disorders, reducing serum cytokines production and significantly relieving pathological symptoms. It's worth noting, that this study provided the first insight into the characterization and mechanistic investigation of an indole-like CRAC channel antagonist. Altogether, the identification of these two highly selective CRAC channel antagonists, coupled with the elucidation of their action mechanisms, not only provides valuable template molecules but also offers profound insights for drug development targeting the CRAC channel.

A review on edible insects in China: Nutritional supply, environmental benefits, and potential applications.

This review explored the potential of edible insects to address the challenges of malnutrition and food security. Although grain production in China has met the Food and Agriculture Organization standards, the shortage of protein supply is still a big issue. Moreover, expanding livestock farming is considered unsustainable and environmentally unfriendly. Edible insects have become an alternative with higher sustainable and ecological properties. There are 324 species of insects currently consumed in China, and they have high nutritional value, with a rich source of protein and unsaturated fatty acids. Insect farming provides numerous benefits, including green feeds for livestock, poultry, and aquaculture, sustainable organic waste management, as well as industrial and pharmaceutical raw materials. The food toxicological evaluations conducted in China indicated that edible insects are safe for general consumption by the Chinese, but allergies and other related food safety issues should not be ignored. Consumer acceptance is another barrier to overcome, with different schemas between China and Western countries. More research on the potential functions of edible insects and their product development may enhance their acceptance in China. Overall, incorporating edible insects into our diet is a promising solution to address challenges related to protein supply and food security. To ensure safety and sustainability, appropriate legislation, quality regulations, large-scale insect farms, and acceptable processing techniques are necessary. Moreover, more scientific research and social awareness are required to promote the culture and utilization of edible insects in China.