Lumbar Apex Position as an Independent Risk Factor for Adjacent Segment Diseases in Patients Undergoing Short-level Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective study. OBJECTIVE: To investigate whether lumbar apex position had an impact on the development of adjacent segment disease (ASD) following transforaminal lumbar interbody fusion (TLIF). SUMMARY OF BACKGROUND DATA: Previous studies have demonstrated that solely concentrating on lumbar lordosis value is not suitable and neglecting the significance of lumbar apex can lead to mechanical complications. However, the relationship between lumbar apex and ASD is still not well understood. METHODS: In this retrospective study, 234 consecutive patients who underwent L3-5 or L4-5 TLIF for degenerative diseases were reviewed. The study evaluated the associations between sagittal parameters and pelvic incidence (PI). Patients were labeled "matched" when lumbar apex position aligned with the theoretical target, and "mismatched" when it did not. Multivariate analysis was applied to find the independent risk factors of ASD. Additionally, a focused sub-analysis was performed based on the lumbar apex position (ideal match, cranial from ideal, and caudal from ideal). RESULTS: After an average follow-up period of 70.6 months, 68 cases were identified as having ASD. Postoperatively, 64.7% (44 out of 68) of the patients with ASD exhibited a mismatched lumbar apex, compared to 41% (68 out of 166) of those without ASD (p < 0.001). PI correlated significantly with proximal lordosis (PL) and lordosis distribution index (LDI), but not with distal lordosis (DL). Multivariate analysis identified age, L3-5 fusion, postoperative DL, and postoperative mismatched lumbar apex as independent risk factors of ASD. Upon the sub-analysis, it was discovered that there were unique compensatory strategies in the cranial and caudal groups, with notable variations in postoperative DL, PL, and LDI among three groups (all p value<0.05). CONCLUSION: Lumbar apex position significantly influenced the risk of ASD. To restore the lumbar apex to its ideal position, a proper value and distribution of DL should be attained.

Surface Modification of Nano-Hydroxyapatite/Polymer Composite for Bone Tissue Repair Applications: A Review.

Nano-hydroxyapatite (n-HA) is the main inorganic component of natural bone, which has been widely used as a reinforcing filler for polymers in bone materials, and it can promote cell adhesion, proliferation, and differentiation. It can also produce interactions between cells and material surfaces through selective protein adsorption and has therefore always been a research hotspot in orthopedic materials. However, n-HA nano-particles are inherently easy to agglomerate and difficult to disperse evenly in the polymer. In addition, there are differences in trace elements between n-HA nano-particles and biological apatite, so the biological activity needs to be improved, and the slow degradation in vivo, which has seriously hindered the application of n-HA in bone fields, is unacceptable. Therefore, the modification of n-HA has been extensively reported in the literature. This article reviewed the physical modification and various chemical modification methods of n-HA in recent years, as well as their modification effects. In particular, various chemical modification methods and their modification effects were reviewed in detail. Finally, a summary and suggestions for the modification of n-HA were proposed, which would provide significant reference for achieving high-performance n-HA in biomedical applications.

Non-alcoholic fatty liver disease changes the expression and activity of hepatic drug-metabolizing enzymes and transporters in rats.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, which can cause serious complications and gradually increase the mortality rate. However, the effects of NAFLD on drug-metabolizing enzymes and transporters remain unclear, which may cause some confusion regarding patient medication. In this study, a NAFLD rat model was constructed by feeding rats with methionine and choline deficiency diets for 6 weeks, and the mRNA and protein levels of drug-metabolizing enzymes and transporter were analyzed by real-time fluorescent quantitative PCR and Western blot, respectively. The activity of drug-metabolizing enzymes was detected by cocktail methods. In the NAFLD rat model, the mRNA expression of phase I enzymes, phase II enzymes, and transporters decreased. At the protein level, only CYP1A1, CYP1B1, CYP2C11, and CYP2J3 presented a decrease. In addition, the activities of CYP1A2, CYP2B1, CYP2C11, CYP2D1, CYP3A2, UGT1A1, UGT1A3, UGT1A6, and UGT1A9 decreased. These changes may be caused by the alteration of FXR, HNF4α, LXRα, LXRß, PXR, and RXR. In conclusion, NAFLD changes the expression and activity of hepatic drug-metabolizing enzymes and transporters in rats, which may affect drug metabolism and pharmacokinetics. In clinical medication, drug monitoring should be strengthened to avoid potential risks.

Hierarchical Recognizing Vector Graphics and A New Chart-based Vector Graphics Dataset.

The conventional approach to image recognition has been based on raster graphics, which can suffer from aliasing and information loss when scaled up or down. In this paper, we propose a novel approach that leverages the benefits of vector graphics for object localization and classification. Our method, called YOLaT (You Only Look at Text), takes the textual document of vector graphics as input, rather than rendering it into pixels. YOLaT builds multi-graphs to model the structural and spatial information in vector graphics and utilizes a dual-stream graph neural network (GNN) to detect objects from the graph. However, for real-world vector graphics, YOLaT only models in flat GNN with vertexes as nodes ignore higher-level information of vector data. Therefore, we propose YOLaT++ to learn Multi-level Abstraction Feature Learning from a new perspective: Primitive Shapes to Curves and Points. On the other hand, given few public datasets focus on vector graphics, data-driven learning cannot exert its full power on this format. We provide a large-scale and challenging dataset for Chart-based Vector Graphics Detection and Chart Understanding, termed VG-DCU, with vector graphics, raster graphics, annotations, and raw data drawn for creating these vector charts. Experiments show that the YOLaT series outperforms both vector graphics and raster graphics-based object detection methods on both subsets of VG-DCU in terms of both accuracy and efficiency, showcasing the potential of vector graphics for image recognition tasks. Our codes, models, and the VG-DCU dataset are available at: https://github.com/microsoft/YOLaT-VectorGraphicsRecognition.

New techniques to identify the tissue of origin for cancer of unknown primary in the era of precision medicine: progress and challenges.

Despite a standardized diagnostic examination, cancer of unknown primary (CUP) is a rare metastatic malignancy with an unidentified tissue of origin (TOO). Patients diagnosed with CUP are typically treated with empiric chemotherapy, although their prognosis is worse than those with metastatic cancer of a known origin. TOO identification of CUP has been employed in precision medicine, and subsequent site-specific therapy is clinically helpful. For example, molecular profiling, including genomic profiling, gene expression profiling, epigenetics and proteins, has facilitated TOO identification. Moreover, machine learning has improved identification accuracy, and non-invasive methods, such as liquid biopsy and image omics, are gaining momentum. However, the heterogeneity in prediction accuracy, sample requirements and technical fundamentals among the various techniques is noteworthy. Accordingly, we systematically reviewed the development and limitations of novel TOO identification methods, compared their pros and cons and assessed their potential clinical usefulness. Our study may help patients shift from empirical to customized care and improve their prognoses.

Learning Domain Invariant Prompt for Vision-Language Models.

Prompt learning stands out as one of the most efficient approaches for adapting powerful vision-language foundational models like CLIP to downstream datasets by tuning learnable prompt vectors with very few samples. However, despite its success in achieving remarkable performance on in-domain data, prompt learning still faces the significant challenge of effectively generalizing to novel classes and domains. Some existing methods address this concern by dynamically generating distinct prompts for different domains. Yet, they overlook the inherent potential of prompts to generalize across unseen domains. To address these limitations, our study introduces an innovative prompt learning paradigm, called MetaPrompt, aiming to directly learn domain invariant prompt in few-shot scenarios. To facilitate learning prompts for image and text inputs independently, we present a dual-modality prompt tuning network comprising two pairs of coupled encoders. Our study centers on an alternate episodic training algorithm to enrich the generalization capacity of the learned prompts. In contrast to traditional episodic training algorithms, our approach incorporates both in-domain updates and domain-split updates in a batch-wise manner. For in-domain updates, we introduce a novel asymmetric contrastive learning paradigm, where representations from the pre-trained encoder assume supervision to regularize prompts from the prompted encoder. To enhance performance on out-of-domain distribution, we propose a domain-split optimization on visual prompts for cross-domain tasks or textual prompts for cross-class tasks during domain-split updates. Extensive experiments across 11 datasets for base-to-new generalization and 4 datasets for domain generalization exhibit favorable performance. Compared with the state-of-the-art method, MetaPrompt achieves an absolute gain of 1.02% on the overall harmonic mean in base-to-new generalization and consistently demonstrates superiority over all benchmarks in domain generalization.

Validation of Roussouly classification in predicting the occurrence of adjacent segment disease after short-level lumbar fusion surgery.

BACKGROUND: Recent studies demonstrated that restoring sagittal alignment to the original Roussouly type can remarkably reduce complication rates after adult spinal deformity surgery. However, there is still no data proving the benefit of maintaining ideal Roussouly shape in the lumbar degenerative diseases and its association with the development of adjacent segment disease (ASD). Thus, this study was performed to validate the usefulness of Roussouly classification to predict the occurrence of ASD after lumbar fusion surgery. MATERIALS AND METHODS: This study retrospectively reviewed 234 consecutive patients with lumbar degenerative diseases who underwent 1- or 2-level fusion surgery. Demographic and radiographic data were compared between ASD and non-ASD groups. The patients were classified by both "theoretical" [based on pelvic incidence (PI)] and "current" (based on sacral slope) Roussouly types. The patients were defined as "matched" if their "current" shapes matched the "theoretical" types and otherwise as "mismatched". The logistic regression analysis was performed to identify the factors associated with ASD. Finally, clinical data and spinopelvic parameters of "theoretical" and "current" types were compared. RESULTS: With a mean follow-up duration of 70.6 months, evidence of ASD was found in the 68 cases. Postoperatively, ASD group had more "current" shapes classified as type 1 or 2 and fewer as type 3 than the non-ASD group (p < 0.001), but the distribution of "theoretical" types was similar between groups. Moreover, 80.9% (55/68) of patients with ASD were mismatched, while 48.2% (80/166) of patients without ASD were mismatched (p < 0.001). A multivariate analysis identified age [odds ratio (OR) = 1.058)], 2-level fusion (OR = 2.9830), postoperative distal lordosis (DL, OR = 0.949) and mismatched Roussouly type (OR = 4.629) as independent risk factors of ASD. Among the four "theoretical" types, type 2 had the lowest lumbar lordosis, DL, and segmental lordosis. When considering the "current" types, current type 2 was associated with higher rates of 2-level fusion, worse DL, and greater pelvic tilt compared with other current types. CONCLUSIONS: DL loss and mismatched Roussouly type were significant risk factors of ASD. To decrease the incidence of ASD, an appropriate value of DL should be achieved to restore sagittal alignment back to the ideal Roussouly type. LEVEL OF EVIDENCE: Level 4.

Validation of age-adjusted pelvic incidence minus lumbar lordosis and lordosis distribution index for assessing adjacent-segment disease after short-level lumbar fusion surgery: minimum 5 years of follow-up.

OBJECTIVE: The purpose of this study was to investigate the influence of sagittal alignment according to age-adjusted pelvic incidence minus lumbar lordosis (PI-LL) and lordosis distribution index (LDI) on the occurrence of adjacent-segment disease (ASD) after lumbar fusion surgery. METHODS: This study retrospectively reviewed 234 consecutive patients with lumbar degenerative diseases who underwent 1- or 2-level lumbar fusion surgery. Demographic and radiographic (preoperative and 3-month postoperative) data were collected and compared between ASD and non-ASD groups. Binary logistic regression analysis was performed to evaluate adjusted associations between potential variables and ASD development. A subanalysis was further conducted to assess their relationships in the range of different PI values. RESULTS: With a mean follow-up duration of 70.6 months (range 60-121 months), 118 patients (50.4%) were diagnosed as having cranial radiological ASD. Univariate analyses showed that older age, 2-level fusion, worse preoperative pelvic tilt and LL, lower pre- and postoperative LDI, and more improvement in sagittal vertical axis were significantly correlated with the occurrence of ASD. No significant differences in the PI-LL and age-adjusted PI-LL (offset) were detected between ASD and non-ASD groups. Multivariate analysis identified postoperative LDI (OR 0.971, 95% CI 0.953-0.989, p = 0.002); 2-level fusion (OR 3.477, 95% CI 1.964-6.157, p < 0.001); and improvement of sagittal vertical axis (OR 0.992, 95% CI 0.985-0.998, p = 0.039) as the independent variables for predicting the occurrence of ASD. When stratified by PI, LDI was identified as an independent risk factor in the groups with low and average PI. Lower segmental lordosis (OR 0.841, 95% CI 0.742-0.954, p = 0.007) could significantly increase the incidence of ASD in the patients with high LDI. CONCLUSIONS: Age-adjusted PI-LL may have limited ability to predict the development of ASD. LDI could exert an important effect on diagnosing the occurrence of ASD in the cases with low and average PI, but segmental lordosis was a more significant risk factor than LDI in individuals with high PI.

Responses of photosynthesis-related genes in Sargassum horneri to high temperature stress.

Golden tide outbreak threatened the marine ecological environment. Sargassum horneri is a single dominant species of the Yellow Sea golden tide, which growth and development are affected by changes in sea water temperature. This study investigated the photosynthetic physiology of copper algae and found that the growth rate, chlorophyll a content, carotenoid content, Fv/Fm, and maximum electron transfer efficiency were significantly reduced, indicating that Sargassum horneri was under stress under high temperature. In this study, high-throughput sequencing was used to analyze the response mechanisms of photosynthesis-related genes in S. horneri under high temperature stress. The results showed that most of the photosynthesis-related genes in S. horneri were downregulated and photosynthesis was inhibited under high temperature stress. However, the expression levels of ferredoxin, ferredoxin-NADP reductase, light-harvesting protein complexes, and oxygen-evolving complex genes were significantly upregulated (P ≤ 0.05) after five days of high temperature treatment. This study found that photosynthesis related genes play a crucial role in regulating the photosynthetic response of S. horneri to high temperature stress.

Helping others but Hurting Yourself? The underlying mechanism linking helping behavior to task performance.

Helping behavior positively influences organizational effectiveness, which is why the importance of this behavior is highlighted in Chinese enterprises, and employees are encouraged to engage in it. However, from an actor-centric perspective, helping behavior is not always beneficial. In this paper, cognitive-affective personality system theory is applied to link helping behavior to task performance, thus enhancing the understanding of the effects of helping behavior. By adopting a two-wave questionnaire survey, data from 202 leader-subordinate dyads were gathered. Then, the BruceR (V0.7.2) package of Rstudio (V4.1.1) was used to generate a multi-mediated moderation model and test the hypotheses. The following results were obtained: 1) Helping behavior was negatively associated with task performance. 2) Cognitive irritation and emotional exhaustion serially mediated the influences of helping behavior on task performance. 3) Team-level communal goal striving moderated the indirect influence of helping behavior on task performance; the indirect influence was only significant when the levels of team communal goal striving were low. From an actor-centric perspective, this paper presents evidence for the connection between helping behavior and task performance. Numerous implications for management approaches are presented to maximize the management of helping behavior.

Construction of humanized CYP1A2 rats using CRISPR/Cas9 to promote drug metabolism and pharmacokinetic research.

Cytochrome P450 family 1 subfamily A member 2 (CYP1A2), performs an indispensable role in metabolism of both exogenous and endogenous substances. What is more, CYP1A2 functions in human diseases by regulating homeostasis of cholesterol. Despite the emergence of gene-editing animal models, genetically humanized animals that overcome species differences for further exploring the role of CYP1A2 in drug metabolism and human diseases have not yet been constructed. In this study, we inserted human CYP1A2 cDNA into the rat Cyp1a2 gene by using CRISPR/Cas9 technology. Results showed that human CYP1A2 was successfully expressed in humanized rat liver and there were no statistically significant differences of physiological symptoms compared with wild-type (WT) rats. In vitro incubation results indicated the different inhibition of furafylline on CYP1A2 activity in human liver microsomes, humanized CYP1A2 (hCYP1A2) rat liver microsomes, and WT rat liver microsomes, with IC50 values of 7.1 µM, 36.5 µM, and 285.8 µM, respectively. Meanwhile, pharmacokinetic characteristics of clozapine were conducted, and the results suggested that in hCYP1A2 rats, clozapine tended to be metabolized into norclozapine. Both the in vitro and in vivo results demonstrated the different metabolic functions of CYP1A2 in humanized and WT rats. We successfully constructed a novel humanized CYP1A2 rat model using the CRISPR/Cas9 system, providing a powerful tool for better predicting CYP1A2-mediated drug metabolism and pharmacokinetics. Significance Statement Human CYP1A2 takes active part both in the biotransformation of exogenous substances and endogenous substances. Meanwhile, it plays a regulatory role in human diseases, including hypercholesterolemia, hypertension as well as various malignant tumors. This study successfully constructed humanized CYP1A2 rat model by CRISPR/Cas9 technology, providing a powerful model for promoting drug development and safety evaluation, as well as further exploring the role of CYP1A2 in human diseases.

Droplet-based high-throughput single microbe RNA sequencing by smRandom-seq.

Bacteria colonize almost all parts of the human body and can differ significantly. However, the population level transcriptomics measurements can only describe the average bacteria population behaviors, ignoring the heterogeneity among bacteria. Here, we report a droplet-based high-throughput single-microbe RNA-seq assay (smRandom-seq), using random primers for in situ cDNA generation, droplets for single-microbe barcoding, and CRISPR-based rRNA depletion for mRNA enrichment. smRandom-seq showed a high species specificity (99%), a minor doublet rate (1.6%), a reduced rRNA percentage (32%), and a sensitive gene detection (a median of ~1000 genes per single E. coli). Furthermore, smRandom-seq successfully captured transcriptome changes of thousands of individual E. coli and discovered a few antibiotic resistant subpopulations displaying distinct gene expression patterns of SOS response and metabolic pathways in E. coli population upon antibiotic stress. smRandom-seq provides a high-throughput single-microbe transcriptome profiling tool that will facilitate future discoveries in microbial resistance, persistence, microbe-host interaction, and microbiome research.

Humanistic care relieves mental distress of inpatients in the shelter hospital during COVID-19 pandemic in Shanghai: a cross-sectional observational study.

Objective: The prevalence of mental distress has been noted in shelter hospitals set up for COVID-19. Potential risk demographic and hospitalization factors were screened. We also aimed to determine whether humanistic care established in the shelter hospital was effective in ameliorating mental distress. Methods: A cross-sectional observational survey-based single-centered study was conducted from 28th April to 5th May 2022 during the COVID-19 pandemic in Shanghai. Asymptomatic adult inpatients and those with mild symptoms were recruited for this study, and humanistic care measures were carried out by the administrative office according to the Work Program on Psychological Assistance and Social Work Services at the Shelter Hospital launched on 5th March 2020. Symptoms of mental distress, such as reported stress, anxiety, depression, and insomnia were measured using the Chinese Stress Response Questionnaire-28, the Chinese version of Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Insomnia Severity Index-7, respectively. Results: In total, 1,246 out of 9,519 inpatients, including 565 (45.35%) women and 681 (54.65%) men, with a median age of 36 years responded to the survey. The overall prevalence of stress, anxiety, depression, and insomnia in inpatients was 94 (7.54%), 109 (8.75%), 141 (11.32%), and 144 (11.56%), respectively. Mental distress was aggravated by COVID-19-related symptoms, comorbidities, and prolonged hospital stays. A stable internet connection was the most effective measure to reduce stress and depression. Offering inpatient with study or work facilitations, and mental health education help to ameliorate anxiety and depression. Organizing volunteering was a potential protective factor against stress. Conclusion: Humanistic care is crucial and effective for protecting against mental distress, which should be emphasized in shelter hospitals.

Does higher education promote sustainable development? Role of green technology and financial performance.

How do digitalizing businesses help them achieve sustainable growth? This research examines the mediating function of green technology innovation in answering this question by defining sustainable development performance in terms of corporations' financial and environmental success. The educational system in China is examined to see how much of an impact it has on eco-innovation, as well as the relationship between green technology and innovation. The IFE test was utilized to determine whether or not the associations between variables such as GDP per capita, urbanization, green technology, higher education, and carbon dioxide emissions will continue to exist between 2004 and 2020 in China. The data for this analysis came from 30 of China's provinces. The findings of both the short-term and long-term CS-ARDL estimations demonstrated a positive link between eco-innovation and GDP per capita, green technology, higher education, and CO2 emissions. On the other hand, a negative correlation was found between urbanization and eco-innovation. The next topic covered in the research was how the effects of green technology might be seen in areas such as GDP per capita, higher education, and carbon dioxide emissions. The findings might provide valuable knowledge that developing economies can use to construct a feasible, sustainable path.

Effect of temperature on betacyanins synthesis and the transcriptome of Suaeda salsa.

Introduction: Suaeda salsa (Linn.) Pall. is an important tourist resource and ecological restoration species in coastal wetlands. Environmental factors such as low temperature, darkness, phytohormone, salt stress and seawater flflooding, and light can induce betalain synthesis in S. salsa, which plays an important role in plant adaptation to abiotic stress processes and in shaping the beautiful "red beach" landscape. Methods: In this study, Illumina sequencing was used to profifile the transcriptome sequence (RNA-Seq) of S. salsa leaves at different temperatures (5° C, 10°C, 15°C, 20°C, 25°C, and 30°C) and to validate differentially expressed genes (DEGs) indicated by real-time PCR (RT-qPCR). Results: The betacyanin content was highest in S. salsa leaves at 15°C. Transcription group data showed that compared to the control group (15°C), the "betacyanin biosynthesis pathway" was signifificantly enriched in the fifive different temperature groups. KEGG analysis showed that the DEGs were mainly involved in pathways of phenylpropanoid biosynthesis, carbon fifixation in photosynthetic organisms, flflavonoid biosynthesis, and betacyanin biosynthesis. Among the key enzymes involved in biosynthesis of betacyanin, genes for tyrosinase, CYP76AD1 and 4,5-DOPA dioxygenase were signifificantly upregulated and most abundantly expressed at 15°C. It is possible that the gene for betacyanin synthesis from S. salsa is primarily regulated by the MYB1R1 and MYB1 transcription factor. Four DEGs were randomly selected for quantitative PCR analysis, and DEG expression was generally consistent with the RNA-Seq data, verifying the validity of the transcriptome sequencing data. Discussion: Relative to other temperatures, 15°C was optimum for S. salsa betacyanin synthesis, and this provides a theoretical reference for coastal wetland ecological remediation, reveals mechanisms of S. salsa discoloration, and further mines its potential application for landscape vegetation.

LncRNA-HOTAIRM1 promotes aerobic glycolysis and proliferation in osteosarcoma via the miR-664b-3p/Rheb/mTOR pathway.

Osteosarcoma (OS), which is a common and aggressive primary bone malignancy, occurs mainly in children and adolescent. Long noncoding RNAs (lncRNAs) are reported to play a pivotal role in various cancers. Here, we found that the lncRNA HOTAIRM1 is upregulated in OS cells and tissues. A set of functional experiments suggested that HOTAIRM1 knockdown attenuated the proliferation and stimulated the apoptosis of OS cells. A subsequent mechanistic study revealed that HOTAIRM1 functions as a competing endogenous RNA to elevate ras homologue enriched in brain (Rheb) expression by sponging miR-664b-3p. Immediately afterward, upregulated Rheb facilitates proliferation and suppresses apoptosis by promoting the mTOR pathway-mediated Warburg effect in OS. In summary, our findings demonstrated that HOTAIRM1 promotes the proliferation and suppresses the apoptosis of OS cells by enhancing the Warburg effect via the miR-664b-3p/Rheb/mTOR axis. Understanding the underlying mechanisms and targeting the HOTAIRM1/miR-664b-3p/Rheb/mTOR axis are essential for OS clinical treatment.

Dynamic associations between the respiratory tract and gut antibiotic resistome of patients with COVID-19 and its prediction power for disease severity.

The antibiotic resistome is the collection of all antibiotic resistance genes (ARGs) present in an individual. Whether an individual's susceptibility to infection and the eventual severity of coronavirus disease 2019 (COVID-19) is influenced by their respiratory tract antibiotic resistome is unknown. Additionally, whether a relationship exists between the respiratory tract and gut ARGs composition has not been fully explored. We recruited 66 patients with COVID-19 at three disease stages (admission, progression, and recovery) and conducted a metagenome sequencing analysis of 143 sputum and 97 fecal samples obtained from them. Respiratory tract, gut metagenomes, and peripheral blood mononuclear cell (PBMC) transcriptomes are analyzed to compare the gut and respiratory tract ARGs of intensive care unit (ICU) and non-ICU (nICU) patients and determine relationships between ARGs and immune response. Among the respiratory tract ARGs, we found that Aminoglycoside, Multidrug, and Vancomycin are increased in ICU patients compared with nICU patients. In the gut, we found that Multidrug, Vancomycin, and Fosmidomycin were increased in ICU patients. We discovered that the relative abundances of Multidrug were significantly correlated with clinical indices, and there was a significantly positive correlation between ARGs and microbiota in the respiratory tract and gut. We found that immune-related pathways in PBMC were enhanced, and they were correlated with Multidrug, Vancomycin, and Tetracycline ARGs. Based on the ARG types, we built a respiratory tract-gut ARG combined random-forest classifier to distinguish ICU COVID-19 patients from nICU patients with an AUC of 0.969. Cumulatively, our findings provide some of the first insights into the dynamic alterations of respiratory tract and gut antibiotic resistome in the progression of COVID-19 and disease severity. They also provide a better understanding of how this disease affects different cohorts of patients. As such, these findings should contribute to better diagnosis and treatment scenarios.

Whole-genome DNA methylation profiling reveals epigenetic signatures in developing muscle in Tan and Hu sheep and their offspring.

Introduction: The Tan sheep is a popular local breed in China because of its tenderness and flavor. The Hu sheep breed is also famous for its high litter size, and its muscle growth rate is faster than that of Tan sheep. However, the epigenetic mechanism behind these muscle-related phenotypes is unknown. Methods: In this study, the longissimus dorsi tissue from 18 6 month-old Tan sheep, Hu sheep, and Tan-Hu F2 generation (6 sheep per population) were collected. After genomic DNA extraction, whole-genome bisulfite sequencing (WGBS) and bioinformatics analysis were performed to construct genome-wide DNA methylome maps for the Tan sheep, Hu sheep and their Tan-Hu F2 generation. Results: Distinct genome-wide DNA methylation patterns were observed between Tan sheep and Hu sheep. Moreover, DNA methylated regions were significantly increased in the skeletal muscle from Tan sheep vs. the F2 generation compared to the Hu sheep vs. F2 generation and the Tan sheep vs. Hu sheep. Compared with Hu sheep, the methylation levels of actin alpha 1 (ACTA1), myosin heavy chain 11 (MYH11), Wiskott-Aldrich syndrome protein (WAS), vav guanine nucleotide exchange factor 1 (VAV1), fibronectin 1 (FN1) and Rho-associated protein kinase 2 (ROCK2) genes were markedly distinct in the Tan sheep. Furthermore, Gene Ontology analysis indicated that these genes were involved in myotube differentiation, myotube cell development, smooth muscle cell differentiation and striated muscle cell differentiation. Conclusion: The findings from this study, in addition to data from previous research, demonstrated that the ACTA1, MYH11, WAS, VAV1, FN1, and ROCK2 genes may exert regulatory effects on muscle development.

Removable carbon and storage carbon of golden tides.

Due to ever-increasing global warming, ocean acidification, and inshore eutrophication, the outbreak of golden tides with Sargassum horneri has increased in the Yellow sea, where the biomass carbon enters three main carbon pathways: a. Removal of carbon from seawater by salvage, known as removable carbon; b. Biomass carbon is deposited to the seafloor through POC and RDOC through Biological Carbon Pump and Microbial Carbon Pump; c. Re-entering the carbon cycle through the food chain or re-entering the atmosphere through the action of microbes. Estimating carbon fixation (removable carbon) and storage (particulate organic carbon (POC) and refractory dissolved organic carbon (RDOC)) is vital in studying the global carbon cycle. In this research, it was observed that the C content of S. horneri was high, and the utilization rate of dissolved organic carbon (DOC), RDOC, and POC was also high in the eutrophication environment, where only 2.71 % of algal biomass carbon was converted to RDOC, and only 0.20 % converted to POC. The C + N + P combination has a restart effect on the seasonal accumulation of RDOC in relevant sea areas. It is suggested that the salvage and resource utilization should be strengthened to effectively control the golden tide and reduce the substantial economic losses to realize the win-win situation of carbon sink and environmental restoration.

MicroRNA-324-3p inhibits osteosarcoma progression by suppressing PGAM1-mediated aerobic glycolysis.

Osteosarcoma (OS) is the most common primary malignant neoplasm of the bone. Recent studies have indicated that the inhibitory effects of microRNA (miR)-324-3p could affect the development of numerous cancers. However, its biological roles and underlying mechanisms in OS progression remain unexplored. In this study, miR-324-3p expression was markedly reduced in OS cell lines and tissues. Functionally, miR-324-3p overexpression suppressed OS progression and was involved in the Warburg effect. Mechanistically, miR-324-3p negatively regulated phosphoglycerate mutase 1 (PGAM1) expression by targeting its 3'-UTR. Moreover, high expression of PGAM1 promoted OS progression and aerobic glycolysis, which were associated with inferior overall survival in patients with OS. Notably, the tumor suppressor functions of miR-324-3p were partially recovered by PGAM1 overexpression. In summary, the miR-324-3p/PGAM1 axis plays an important role in regulating OS progression by controlling the Warburg effect. Our results provide mechanistic insights into the function of miR-324-3p in glucose metabolism and subsequently on the progression of OS. Targeting the miR-324-3p/PGAM1 axis could be a promising molecular strategy for the treatment of OS.