Gut microbiota characteristics of colorectal cancer patients in Hubei, China, and differences with cohorts from other Chinese regions.

The research on the correlation or causality between gut microbiota and the occurrence, development, and treatment of colorectal cancer (CRC) is receiving increasing emphasis. At the same time, the incidence and mortality of colorectal cancer vary among individuals and regions, as does the gut microbiota. In order to gain a better understanding of the characteristics of the gut microbiota in CRC patients and the differences between different regions, we initially compared the gut microbiota of 25 CRC patients and 26 healthy controls in the central region of China (Hubei Province) using 16S rRNA high-throughput sequencing technology. The results showed that Corynebacterium, Enterococcus, Lactobacillus, and Escherichia-Shigella were significantly enriched in CRC patients. In addition, we also compared the potential differences in functional pathways between the CRC group and the healthy control group using PICRUSt's functional prediction analysis. We then analyzed and compared it with five cohort studies from various regions of China, including Central, East, and Northeast China. We found that geographical factors may affect the composition of intestinal microbiota in CRC patients. The composition of intestinal microbiota is crucial information that influences colorectal cancer screening, early detection, and the prediction of CRC treatment outcomes. This emphasizes the importance of conducting research on CRC-related gut microbiota in various regions of China.

Ultra-high-precision pneumatic force servo system based on a novel improved particle swarm optimization algorithm integrating Gaussian mutation and fuzzy theory.

In this study, an ultra-high-precision pneumatic force servo system (UPFSS) is proposed. On the one hand, a novel air-floating pneumatic cylinder (AFPC) with an air-floating piston capable of independent air supply and exhaust is developed for this system, and its special flow channel design allows the air-floating piston to be suspended in the cylinder without being constrained by the pressure in the chambers. The friction force of the AFPC is less than 0.0049 N. On the other hand, a leakage chamber is constructed to simulate the clearance between the air-floating piston and the cylinder wall, and a fuzzy proportional integral (FPI)-based pressure control system (PCS) is designed for the simulated leakage chamber. Furthermore, a novel particle swarm optimization algorithm integrating Gaussian mutation and fuzzy theory (IGF-PSO) is presented. After testing, the IGF-PSO algorithm is found to have outstanding optimization performance. Then, the parameters of the FPI controller are optimized through the IGFPSO algorithm. Experimental comparisons reveal that the steady-state error achieved by the parameter-optimized pressure controller in response to the leakage condition is about 38 % smaller than that achieved by the pressure controller with parameters obtained using the trial-and-error method. Finally, the UPFSS is tested by using the optimized PCS to supply compressed air to the chamber of the AFPC. The results show that the UPFSS achieves a steady-state error of no more than 0.0279 N in the continuous step response within the range of 240 N.

0.01% Atropine Eye Drops in Children With Myopia and Intermittent Exotropia: The AMIXT Randomized Clinical Trial.

Importance: Exotropia and myopia are commonly coexistent. However, evidence is limited regarding atropine interventions for myopia control in children with myopia and intermittent exotropia (IXT). Objective: To evaluate the efficacy and safety of 0.01% atropine eye drops on myopia progression, exotropia conditions, and binocular vision in individuals with myopia and IXT. Design, Setting, and Participants: This placebo-controlled, double-masked, randomized clinical trial was conducted from December 2020 to September 2023. Children aged 6 to 12 years with basic-type IXT and myopia of -0.50 to -6.00 diopters (D) after cycloplegic refraction in both eyes were enrolled. Intervention: Participants were randomly assigned in a 2:1 ratio to 0.01% atropine or placebo eye drops administered in both eyes once at night for 12 months. Main Outcomes and Measures: The primary outcome was change in cycloplegic spherical equivalent from baseline at 1 year. Secondary outcomes included change in axial length (AL), accommodative amplitude (AA), exotropia conditions, and binocular vision at 1 year. Results: Among 323 screened participants, 300 children (mean [SD] age, 9.1 [1.6] years; 152 male [50.7%]) were included in this study. A total of 200 children (66.7%) were in the atropine group, and 100 (33.3%) were in the placebo group. At 1 year, the 0.01% atropine group had slower spherical equivalent progression (-0.51 D vs -0.75 D; difference = 0.24 D; 95% CI, 0.11-0.37 D; P < .001) and AL elongation (0.31 mm vs 0.42 mm; difference = -0.11 mm; 95% CI, -0.17 to -0.06 mm; P < .001) than the placebo group. The mean AA change was -3.06 D vs 0.12 D (difference = -3.18 D; 95% CI, -3.92 to -2.44 D; P < .001) in the atropine and placebo groups, respectively. The 0.01% atropine group had a decrease in near magnitude of exodeviation whereas the placebo group had an increase (-1.25 prism diopters [PD] vs 0.74 PD; difference = -1.99 PD; 95% CI, -3.79 to -0.19 PD; P = .03). In the atropine vs placebo group, respectively, the incidence of study drug-related photophobia was 6.0% (12 of 200 participants) vs 8.0% (8 of 100 participants; difference = -2.0%; 95% CI, -9.4% to 3.7%; P = .51) and for blurred near vision was 6.0% (12 of 200 participants) vs 7.0% (7 of 100 participants) (difference = -1.0%; 95% CI, -8.2% to 4.5%; P = .74). Conclusions and Relevance: The findings of this randomized clinical trial support use of 0.01% atropine eye drops, although compromising AA to some extent, for slowing myopia progression without interfering with exotropia conditions or binocular vision in children with myopia and IXT. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000039827.

The pathogenicity of PSEN2 variants is tied to Aß production and homology to PSEN1.

INTRODUCTION: Though recognized as a potential cause of Autosomal Dominant Alzheimer's Disease, the pathogenicity of many PSEN2 variants remains uncertain. We compared Aß production across all missense PSEN2 variants in the Alzforum database and, when possible, to corresponding PSEN1 variants. METHODS: We expressed 74 PSEN2 variants, 21 of which had homologous PSEN1 variants with the same amino acid substitution, in HEK293 cells lacking PSN1/2. Aß production was compared to age at symptom onset (AAO) and between homologous PSEN1/2 variants. RESULTS: Aß42/40 and Aß37/42 ratios were associated with AAO across PSEN2 variants, strongly driven by PSEN2 variants with PSEN1 homologs. PSEN2 AAO was 18.3 years later compared to PSEN1 homologs. Aß ratios from PSEN1 / 2 homologs were highly correlated, suggesting a similar mechanism of γ-secretase dysfunction. DISCUSSION: The existence of a PSEN1 homolog and patterns of Aß production are important considerations in assessing the pathogenicity of previously-reported and new PSEN2 variants.

Characterization of linoleate dioxygenases in basidiomycetes and the functional role of CcLdo1 in regulating fruiting body development in Coprinopsis cinerea.

Coprinopsis cinerea, a model fungus, is utilized for investigating the developmental mechanisms of basidiomycetes. The development of basidiomycetes is a highly organized process that requires coordination among genetic, environmental, and physiological factors. Oxylipins, a class of widely distributed signaling molecules, play crucial roles in fungal biology. Among oxylipins, the sexual pheromone-inducing factors (psi factors) have been identified as key regulators of the balance between asexual and sexual spore development in Ascomycetes. Linoleate dioxygenases are enzymes involved in the biosynthesis of psi factors, yet their specific physiological functions in basidiomycete development remain unclear. In this study, linoleate dioxygenases in basidiomycetes were identified and characterized. Phylogenetic analysis revealed that linoleate dioxygenases from Basidiomycota formed a distinct clade, with linoleate dioxygenases from Agaricomycetes segregating into three groups and those from Ustilaginomycetes forming a separate group. Both basidiomycete and ascomycete linoleate dioxygenases shared two characteristic domains: the N-terminal of linoleate dioxygenase domain and the C-terminal of cytochrome P450 domain. While the linoleate dioxygenase domains exhibited similarity between basidiomycetes and ascomycetes, the cytochrome P450 domains displayed high diversity in key sites. Furthermore, the gene encoding the linoleate dioxygenase Ccldo1 in C. cinerea was knocked out, resulting in a significant increase in fruiting body formation without affecting asexual conidia production. This observation suggests that secondary metabolites synthesized by CcLdo1 negatively regulate the sexual reproduction process in C. cinerea while not influencing the asexual reproductive process. This study represents the first identification of a gene involved in secondary metabolite synthesis that regulates basidiocarp development in a basidiomycete.

Metatranscriptomics-guided genome-scale metabolic reconstruction reveals the carbon flux and trophic interaction in methanogenic communities.

BACKGROUND: Despite rapid advances in genomic-resolved metagenomics and remarkable explosion of metagenome-assembled genomes (MAGs), the function of uncultivated anaerobic lineages and their interactions in carbon mineralization remain largely uncertain, which has profound implications in biotechnology and biogeochemistry. RESULTS: In this study, we combined long-read sequencing and metatranscriptomics-guided metabolic reconstruction to provide a genome-wide perspective of carbon mineralization flow from polymers to methane in an anaerobic bioreactor. Our results showed that incorporating long reads resulted in a substantial improvement in the quality of metagenomic assemblies, enabling the effective recovery of 132 high-quality genomes meeting stringent criteria of minimum information about a metagenome-assembled genome (MIMAG). In addition, hybrid assembly obtained 51% more prokaryotic genes in comparison to the short-read-only assembly. Metatranscriptomics-guided metabolic reconstruction unveiled the remarkable metabolic flexibility of several novel Bacteroidales-affiliated bacteria and populations from Mesotoga sp. in scavenging amino acids and sugars. In addition to recovering two circular genomes of previously known but fragmented syntrophic bacteria, two newly identified bacteria within Syntrophales were found to be highly engaged in fatty acid oxidation through syntrophic relationships with dominant methanogens Methanoregulaceae bin.74 and Methanothrix sp. bin.206. The activity of bin.206 preferring acetate as substrate exceeded that of bin.74 with increasing loading, reinforcing the substrate determinantal role. CONCLUSION: Overall, our study uncovered some key active anaerobic lineages and their metabolic functions in this complex anaerobic ecosystem, offering a framework for understanding carbon transformations in anaerobic digestion. These findings advance the understanding of metabolic activities and trophic interactions between anaerobic guilds, providing foundational insights into carbon flux within both engineered and natural ecosystems. Video Abstract.

A targeting nanoplatform for chemo-photothermal synergistic therapy of small-cell lung cancer.

The precise delivery of drugs to tumor sites and the thermoresistance of tumors remain major challenges in photothermal therapy (PTT). Somatostatin receptor 2 (SSTR2) is proposed as an ideal target for the precise treatment of SCLC. We developed a targeting nano-drug delivery system comprising anti-SSTR2 monoclonal antibody (MAb) surface-modified nanoparticles co-encapsulating Cypate and gambogic acid (GA). The formed SGCPNs demonstrated excellent monodispersity, physiological stability, preferable biocompatibility, and resultant efficient photothermal conversion efficacy. SGCPNs were quickly internalized by SSTR2-overexpressing SCLC cells, triggering the release of GA under acidic and near-infrared (NIR) laser irradiation environments, leading to their escape from lysosomes to the cytosol and then diffusion into the nucleus. SGCPNs can not only decrease the cell survival rate but also inhibit the activity of heat shock protein 90 (HSP90). SGCPNs can be precisely delivered to xenograft tumors of SSTR2-positive SCLC in vivo. Upon NIR laser irradiation, therapy of SGCPNs showed significant tumor regression. In conclusion, SGCPNs provide a new chemo-photothermal synergistic treatment strategy for targeting SCLC.

Improving knowledge, attitude and practice on norovirus infection diarrhea among staff of kindergartens and schools: a before-after study.

BACKGROUND: Norovirus gastroenteritis outbreaks were common in schools and kindergartens and were more related to faculty knowledge, attitude, and practice level. Gastroenteritis outbreaks caused by norovirus in educational institutions were the prominent cause of Public Health Emergency Events in China. This study aimed to explore the transformation in the contribution of KAP items related to outbreak prevention before and after intervention and the impact of demography factors on the intervention. METHODS: This study sampled 1095 kindergarten and 1028 school staff in Shenzhen, China. We created a questionnaire consisting of 35 items in 4 parts, and each item was rated on a scale of 1-5 according to the accuracy. Univariate analysis of non-parametric tests and binary logistic regression were used to estimate the score difference on demographic characteristics, each item and KAP. The odds ratios (OR) with 95% confidence and intervals (CI) for the association between statistical indicators were mainly used to explain the effects before and after intervention. RESULTS: Overall, 98.72% and 74.9% of the kindergarten and school participants were female, and all respondents had the highest scores difference of practice. Following intervention, univariate analysis indicated that primary school and female respondents achieved higher knowledge scores. Staff age beyond 35 (OR = 0.56, CI:0.34-0.92; OR = 0.67, CI:0.50-0.90) and with more than ten years of service (OR = 0.58, CI:0.36-0.91; OR = 0.38, CI:0.17-0.84) demonstrated a significantly lower post-intervention score for attitude and practice in both kindergartens and schools. The staff members exhibited a general lack of familiarity with the transmission of aerosols and the seasonal patterns of NoVs diarrhea pandemics. Item analysis revealed that kindergarten staff aged 26 and above demonstrated superior performance in terms of the efficacy of medical alcohol for inactivation (OR = 1.93, CI:1.13-3.31) and management strategies for unexplained vomiting among students (OR = 1.97, CI:1.21-3.18). Private school personnel displayed more significant improvement in their practices following educational interventions. School administrators' negative attitudes were primarily evident in their perspectives on morning inspections (OR = 0.11, CI:0.05-0.84). CONCLUSIONS: The potential negative impact of faculty age on NoVs-related knowledge can be mitigated by the positive attitudes fostered through seniority. Furthermore, it is imperative to urgently address the lack of knowledge among administrators, and the identification and treatment of vomiting symptoms should be emphasized as crucial aspects of school prevention strategies. Therefore, education authorities should implement comprehensive public health interventions in the future.

Needle-scalpel therapy inhibits the apoptosis of nucleus pulposus cells via the SDF-1/CXCR4 axis in a rat degenerative cervical intervertebral disc model.

As a common disease, cervical spondylosis (CS) results from the degeneration of the cervical intervertebral disc. However, there are still no effective clinical strategies for the treatment of this disease. Needle-scalpel (Ns), a therapy guided by traditional Chinese medicine theory, alleviates intervertebral disc degradation and is widely used in the clinic to treat CS. Stromal cell-derived factor-1 (SDF-1) and its receptor CXC receptor 4 (CXCR4) in nucleus pulposus cells play an important role in CS onset and development. This study aimed to explore whether Ns can relieve pain and regulate the SDF-1/CXCR4 axis in nucleus pulposus cells to inhibit apoptosis, thereby delaying cervical intervertebral disc degradation in a rat model of CS. It was found that the Ns-treated groups exhibited higher mechanical allodynia scores than the model group, and H&E staining, MRI, and scanning electron microscopy revealed that Ns therapy inhibited intervertebral disc degeneration. Additionally, Ns therapy significantly inhibited increases in the RNA and protein expression levels of SDF-1 and CXCR4. Furthermore, these treatments alleviated the apoptosis of nucleus pulposus cells, which manifested as a decline in the proportion of apoptotic nucleus pulposus cells and inhibition of the decrease in the levels of Bcl-2/Bax. These findings indicated that Ns mitigated CS-induced pain, inhibited the apoptosis of nucleus pulposus cells, and alleviated intervertebral disc degeneration in CS rats. These effects may be mediated by specifically regulating the SDF-1/CXCR4 signaling axis. Based on these findings, we conclude that Ns might serve as a promising therapy for the treatment of CS.

[Effects of "brain-gut coherence" method of acupuncture on motor function and intestinal microflora in the patients with cerebral ischemic stroke].

OBJECTIVE: To observe the clinical effect of "brain-gut coherence" method of acupuncture on cerebral ischemic stroke (CIS) and explore its action mechanism. METHODS: A total of 82 patients with CIS were randomly divided into an observation group (41 cases, 3 cases dropped out, 2 cases discontinued) and a control group (41 cases, 4 cases dropped out, 2 cases excluded). The conventional basic treatment was administered in the two groups. Additionally, in the observation group, "brain-gut coherence" method of acupuncture was delivered. The stimulating points included the parietal and temporal anterior oblique line on the affected side, Zhongwan (CV 12), Guanyuan (CV 4), and bilateral Tianshu (ST 25), Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39). In the control group, the routine acupuncture was operated at Baihui (GV 20), Yintang (GV 24+), bilateral Fengchi (GB 20) and Zusanli (ST 36), and Hegu (LI 4), Jianyu (LI 15), Quchi (LI 11), Waiguan (TE 5), Futu (ST 32), Sanyinjiao (SP 6) and Taichong (LR 3) on the affected side. Acupuncture stimulation lasted 30 min each time, once daily, and for 5 days a week. The intervention for 4 weeks was required. The scores of Fugl-Meyer assessment scale (FMA), Berg balance scale (BBS) and the modified Barthel index (MBI), as well as the score of gastrointestinal symptoms were compared before and after treatment in the two groups. The neutrophil count (NUE) and the content of the serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) were detected before and after treatment in the two groups. Using 16S rRNA gene sequencing, the structure and relative abundance of intestinal microflora was detected before and after treatment; and with the enzyme linked immunosorbent assay (ELISA) adopted, the levels of intestinal fatty acid-binding protein (iFABP), D-lactate (D-LA), lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP), tumor necrosis factor-α(TNF-α), interleukin (IL)-1ß and IL-6 in the serum were detected before and after treatment in the two groups. RESULTS: After treatment, the scores of FMA, BBS and MBI were increased (P<0.05), and the scores of gastrointestinal symptoms were decreased (P<0.05) compared with those before treatment in the two groups. Compared with the control group, the scores of FMA, BBS and MBI were higher (P<0.05) and the score of gastrointestinal symptoms was lower (P<0.05) in the observation group after treatment. NEU and the content of serum NT-proBNP were reduced in the two groups (P<0.05), and the content of serum NT-proBNP in the observation group was lower than that of the control group (P<0.05) after treatment. Chao1, Ace, Sobs and Shannon indexes were increased after treatment compared with those before treatment in the two groups (P<0.05); and these indexes in the observation group were higher when compared with the control group (P<0.05). After treatment, the relative abundance of Bacteroidaceae, Enterobacteriaceae, Oscillospiraceae, Streptococcaceae and Sutterellaceae was reduced in comparison with that before treatment in the two groups (P<0.05); and the relative abundance of these microflora was lower in the observation group when compared with the control group (P<0.05). After treatment, the relative abundance of Lachnospiraceae, Ruminococcaceae, Bifidobacteriaceae and Coriobacteriaceae was increased in comparison with that before treatment in the two groups (P<0.05); and the relative abundance of these microflora was elevated in the observation group when compared with the control group (P<0.05). After treatment, the levels of iFABP, D-LA, LPS, LBP, TNF-α, IL-1ß and IL-6 were reduced when compared with those before treatment in the two groups (P<0.05), and these levels of the observation group were lower than those of the control group (P<0.05). CONCLUSION: "Brain-gut coherence" method of acupuncture can improve the motor function and gastrointestinal function of the patients with cerebral ischemic stroke, which may be related to modulating the structure of intestinal microflora, alleviating inflammatory reactions and accelerating the intestinal barrier repair.

Revolutionizing thoracic surgery education: a bibliometric analysis of the past decade's literature.

OBJECTIVES: Thoracic surgery is a complex field requiring advanced technical skills and critical decision-making. Surgical education must evolve to equip trainees with proficiency in new techniques and technologies. METHODS: This bibliometric analysis systematically reviewed 113 articles on thoracic surgery skills training published over the past decade, retrieved from databases including Web of Science. Publication trends, citation analysis, author and journal productivity, and keyword frequencies were evaluated. RESULTS: The United States contributed the most publications, led by pioneering institutions. Simulation training progressed from basic to sophisticated modalities and virtual reality emerged with transformative potential. Minimally invasive techniques posed unique learning challenges requiring integrated curricula. CONCLUSION: Ongoing investments in educational research and curriculum innovations are imperative to advance thoracic surgery training through multidisciplinary strategies. This study provides an evidentiary foundation to optimize training and address the complexities of modern thoracic surgery.

The ischemia-enhanced myocardial infarction protection-related lncRNA protects against acute myocardial infarction.

Long non-coding RNA RP11-64B16.4 (myocardial infarction protection-related lncRNA [MIPRL]) is among the most abundant and the most upregulated lncRNAs in ischemic human hearts. However, its role in ischemic heart disease is unknown. We found MIPRL was conserved between human and mouse and its expression was increased in mouse hearts after acute myocardial infarction (AMI) and in cultured human and mouse cardiomyocytes after hypoxia. The infarcted size, cardiac cell apoptosis, cardiac dysfunction, and cardiac fibrosis were aggravated in MIPRL knockout mice after AMI. The above adverse results could be reversed by re-expression of MIPRL via adenovirus expressing MIPRL. Both in vitro and in vivo, we identified that heat shock protein beta-8 (HSPB8) was a target gene of MIPRL, which was involved in MIPRL-mediated anti-apoptotic effects on cardiomyocytes. We further discovered that MIPRL could combine with the messenger RNA (mRNA) of HSPB8 and increase its expression in cardiomyocytes by enhancing the stability of HSPB8 mRNA. In summary, we have found for the first time that the ischemia-enhanced lncRNA MIPRL protects against AMI via its target gene HSPB8. MIPRL might be a novel promising therapeutic target for ischemic heart diseases such as AMI.

Multi-FusNet: fusion mapping of features for fine-grained image retrieval networks.

As the diversity and volume of images continue to grow, the demand for efficient fine-grained image retrieval has surged across numerous fields. However, the current deep learning-based approaches to fine-grained image retrieval often concentrate solely on the top-layer features, neglecting the relevant information carried in the middle layer, even though these information contains more fine-grained identification content. Moreover, these methods typically employ a uniform weighting strategy during hash code mapping, risking the loss of critical region mapping-an irreversible detriment to fine-grained retrieval tasks. To address the above problems, we propose a novel method for fine-grained image retrieval that leverage feature fusion and hash mapping techniques. Our approach harnesses a multi-level feature cascade, emphasizing not just top-layer but also intermediate-layer image features, and integrates a feature fusion module at each level to enhance the extraction of discriminative information. In addition, we introduce an agent self-attention architecture, marking its first application in this context, which steers the model to prioritize on long-range features, further avoiding the loss of critical regions of the mapping. Finally, our proposed model significantly outperforms existing state-of-the-art, improving the retrieval accuracy by an average of 40% for the 12-bit dataset, 22% for the 24-bit dataset, 16% for the 32-bit dataset, and 11% for the 48-bit dataset across five publicly available fine-grained datasets. We also validate the generalization ability and performance stability of our proposed method by another five datasets and statistical significance tests. Our code can be downloaded from https://github.com/BJFU-CS2012/MuiltNet.git.

Natural Language Processing-Driven Artificial Intelligence Models for the Diagnosis of Lumbar Disc Herniation with L5 and S1 Radiculopathy: A Preliminary Evaluation.

OBJECTIVE: To develop and validate natural language processing-driven artificial intelligence (AI) models for the diagnosis of lumbar disc herniation (LDH) with L5 and S1 radiculopathy using electronic health records (EHRs). METHODS: EHRs of patients undergoing single-level percutaneous endoscopic lumbar discectomy for the treatment of LDH at the L4/5 or L5/S1 level between June 1, 2013, and December 31, 2021, were collected. The primary outcome was LDH with L5 and S1 radiculopathy, which was defined as nerve root compression recorded in the operative notes. Datasets were created using the history of present illness text and positive symptom text with radiculopathy (L5 or S1), respectively. The datasets were randomly split into a training set and a testing set in a 7:3 ratio. Two machine learning models, the long short-term memory network and Extreme Gradient Boosting, were developed using the training set. Performance evaluation of the models on the testing set was done using measures such as the receiver operating characteristic curve, area under the curve, accuracy, recall, F1-score, and precision. RESULTS: The study included a total of 1681 patients, with 590 patients having L5 radiculopathy and 1091 patients having S1 radiculopathy. Among the 4 models developed, the long short-term memory model based on positive symptom text showed the best discrimination in the testing set, with precision (0.9054), recall (0.9405), accuracy (0.8950), F1-score (0.9226), and area under the curve (0.9485). CONCLUSIONS: This study provides preliminary validation of the concept that natural language processing-driven AI models can be used for the diagnosis of lumbar disease using EHRs. This study could pave the way for future research that may develop more comprehensive and clinically impactful AI-driven diagnostic systems.

Metabolomics and transcriptomics analysis revealed the response mechanism of alfalfa to combined cold and saline-alkali stress.

Cold and saline-alkali stress are frequently encountered by plants, and they often occur simultaneously in saline-alkali soils at mid to high latitudes, constraining forage crop distribution and production. However, the mechanisms by which forage crops respond to the combination of cold and saline-alkali stress remain unknown. Alfalfa (Medicago sativa L.) is one of the most essential forage grasses in the world. In this study, we analyzed the complex response mechanisms of two alfalfa species (Zhaodong [ZD] and Blue Moon [BM]) to combined cold and saline-alkali stress using multi-omics. The results revealed that ZD had a greater ability to tolerate combined stress than BM. The tricarboxylic acid cycles of the two varieties responded positively to the combined stress, with ZD accumulating more sugars, amino acids, and jasmonic acid. The gene expression and flavonoid content of the flavonoid biosynthesis pathway were significantly different between the two varieties. Weighted gene co-expression network analysis and co-expression network analysis based on RNA-Seq data suggested that the MsMYB12 gene may respond to combined stress by regulating the flavonoid biosynthesis pathway. MsMYB12 can directly bind to the promoter of MsFLS13 and promote its expression. Moreover, MsFLS13 overexpression can enhance flavonol accumulation and antioxidant capacity, which can improve combined stress tolerance. These findings provide new insights into improving alfalfa resistance to combined cold and saline-alkali stress, showing that flavonoids are essential for plant resistance to combined stresses, and provide theoretical guidance for future breeding programs.

Utilizing Geographical Distribution Statistical Data to Improve Zero-Shot Species Recognition.

Species recognition is a crucial part of understanding the abundance and distribution of various organisms and is important for biodiversity conservation and management. Traditional vision-based deep learning-driven species recognition requires large amounts of well-labeled, high-quality image data, the collection of which is challenging for rare and endangered species. In addition, recognition methods designed based on specific species have poor generalization ability and are difficult to adapt to new species recognition scenarios. To address these issues, zero-shot species recognition based on Contrastive Language-Image Pre-training (CLIP) has become a research hotspot. However, previous studies have primarily utilized visual descriptive information and taxonomic information of species to improve zero-shot recognition performance, and the use of geographic distribution characteristics of species to improve zero-shot recognition performance has not been explored. To fill this gap, we proposed a CLIP-driven zero-shot species recognition method that incorporates knowledge of the geographic distribution of species. First, we designed three prompts based on the species geographic distribution statistical data. Then, the latitude and longitude coordinate information attached to each image in the species dataset was converted into addresses, and they were integrated together to form the geographical distribution knowledge of each species. Finally, species recognition results were derived by calculating the similarity after acquiring features by the trained CLIP image encoder and text encoder. We conducted extensive experiments on multiple species datasets from the iNaturalist 2021 dataset, where the zero-shot recognition accuracies of mammals, mollusks, reptiles, amphibians, birds, and insects were 44.96%, 15.27%, 17.51%, 9.47%, 28.35%, and 7.03%, an improvement of 2.07%, 0.48%, 0.35%, 1.12%, 1.64%, and 0.61%, respectively, as compared to CLIP with default prompt. The experimental results show that the fusion of geographic distribution statistical data can effectively improve the performance of zero-shot species recognition, which provides a new way to utilize species domain knowledge.

Predictive Roles of Basal Metabolic Rate and Muscle Mass in Lung Function among Patients with Obese Asthma: A Prospective Cohort Study.

BACKGROUND: The metabolic-status-related mechanisms underlying the deterioration of the lung function in obese asthma have not been completely elucidated. OBJECTIVE: This study aimed to investigate the basal metabolic rate (BMR) in patients with obese asthma, its association with the lung function, and its mediating role in the impact of obesity on the lung function. METHODS: A 12-month prospective cohort study (n = 598) was conducted in a real-world setting, comparing clinical, body composition, BMR, and lung function data between patients with obese (n = 282) and non-obese (n = 316) asthma. Path model mediation analyses for the BMR and skeletal muscle mass (SMM) were conducted. We also explored the effects of the BMR on the long-term lung function in patients with asthma. RESULTS: Patients with obese asthma exhibited greater airway obstruction, with lower FEV1 (1.99 vs. 2.29 L), FVC (3.02 vs. 3.33 L), and FEV1/FVC (65.5 vs. 68.2%) values compared to patients with non-obese asthma. The patients with obese asthma also had higher BMRs (1284.27 vs. 1210.08 kcal/d) and SMM (23.53 vs. 22.10 kg). Both the BMR and SMM mediated the relationship between obesity and the lung function spirometers (FEV1, %FEV1, FVC, %FVC, and FEV1/FVC). A higher BMR or SMM was associated with better long-term lung function. CONCLUSIONS: Our study highlights the significance of the BMR and SMM in mediating the relationship between obesity and spirometry in patients with asthma, and in determining the long-term lung function. Interventions for obese asthma should focus not only on reducing adiposity but also on maintaining a high BMR.

Lipid Nanoparticles Outperform Electroporation in Delivering Therapeutic HPV DNA Vaccines.

Therapeutic HPV vaccines that induce potent HPV-specific cellular immunity and eliminate pre-existing infections remain elusive. Among various candidates under development, those based on DNA constructs are considered promising because of their safety profile, stability, and efficacy. However, the use of electroporation (EP) as a main delivery method for such vaccines is notorious for adverse effects like pain and potentially irreversible muscle damage. Moreover, the requirement for specialized equipment adds to the complexity and cost of clinical applications. As an alternative to EP, lipid nanoparticles (LNPs) that are already commercially available for delivering mRNA and siRNA vaccines are likely to be feasible. Here, we have compared three intramuscular delivery systems in a preclinical setting. In terms of HPV-specific cellular immune responses, mice receiving therapeutic HPV DNA vaccines encapsulated with LNP demonstrated superior outcomes when compared to EP administration, while the naked plasmid vaccine showed negligible responses, as expected. In addition, SM-102 LNP M exhibited the most promising results in delivering candidate DNA vaccines. Thus, LNP proves to be a feasible delivery method in vivo, offering improved immunogenicity over traditional approaches.

[Research on portable airway impedance monitoring device based on expiratory oscillation].

Monitoring airway impedance has significant clinical value in accurately assessing and diagnosing pulmonary function diseases at an early stage. To address the issue of large oscillator size and high power consumption in current pulmonary function devices, this study adopts a new strategy of expiration-driven oscillation. A lightweight and low-power airway impedance monitoring system with integrated sensing, control circuitry, and dynamic feedback system, providing visual feedback on the system's status, was developed. The respiratory impedance measurement experiments and statistical comparisons indicated that the system could achieve stable measurement of airway impedance at 5 Hz. The frequency spectrum curves of respiratory impedance ( R and X) showed consistent trends with those obtained from the clinical pulmonary function instrument, specifically the impulse oscillometry system (IOS). The differences between them were all less than 1.1 cm H 2O·s/L. Additionally, there was a significant statistical difference in the respiratory impedance R5 between the exercise and rest groups, which suggests that the system can measure the variability of airway resistance parameters during exercise. Therefore, the impedance monitoring system developed in this study supports subjects in performing handheld, continuous measurements of dynamic changes in airway impedance over an extended period of time. This research provides a foundation for further developing low-power, portable, and even wearable devices for dynamic monitoring of pulmonary function.