SNORD3A Regulates STING Transcription to Promote Ferroptosis in Acute Kidney Injury.

Acute kidney injury (AKI) signifies a sudden and prolonged decline in kidney function characterized by tubular cell death and interstitial inflammation. Small nucleolar RNAs (snoRNAs) play pivotal roles in oxidative stress and inflammation, and may play an important role in the AKI process, which remains elusive. an elevated expression of Snord3a is revealed in renal tubules in response to AKI and demonstrates that Snord3a deficiency alleviates renal injury in AKI mouse models. Notably, the deficiency of Snord3a exhibits a mitigating effect on the stimulator of interferon genes (STING)-associated ferroptosis phenotypes and the progression of tubular injury. Mechanistically, Snord3a is shown to regulate the STING signaling axis via promoting STING gene transcription; administration of Snord3a antisense oligonucleotides establishes a significant therapeutic advantage in AKI mouse models. Together, the findings elucidate the transcription regulation mechanism of STING and the crucial roles of the Snord3a-STING axis in ferroptosis during AKI, underscoring Snord3a as a potential prognostic and therapeutic target for AKI.

Effect of multicomponent exercise intervention in community dwelling frail elderly: A systematic review and meta-analysis.

OBJECTIVE: To assess the impact of multicomponent exercises on physical functions of frail elderly in communities, evaluating their effect on muscle strength, balance, and endurance, and their influence on quality of life. METHOD: PubMed, Embase, Cochrane, and Web of Science were searched to collect relevant randomized controlled trials. The search cutoff date was January 24, 2024. Included studies met pre-specified inclusion and exclusion criteria. Data analysis was performed using Revman 5.4 and Stata 15.0 software. RESULT: This analysis included 19 studies. After 12 weeks, the multicomponent exercises significantly enhanced participants' performance in various physical function assessments. Specifically, in the Timed Up and Go Test, the exercise group showed a significant reduction in time [SMD = -0.86 (95 % CI: -1.40 to -0.33)]. In the Short Physical Performance Battery, interventions shorter than 6 weeks significantly increased scores [SMD = 1.01 (95 % CI: 0.64 to 1.37)], and those longer than 6 weeks showed improvements [SMD = 0.53 (95 % CI: 0.26 to 0.80)]. Muscle strength also improved, with handgrip strength and knee extensor strength enhancements [SMD = 0.93 (95 % CI: 0.27 to 1.59); SMD = 0.72 (95 % CI: 0.24 to 1.20)]. However, there was no statistically significant difference in walking speed between the groups [SMD = 0.04 (95 % CI: -0.33 to 0.40)]. CONCLUSION: Although multicomponent exercises significantly improve muscle strength, balance, and endurance in frail elderly individuals, there is no conclusive evidence of their effect on enhancing quality of life or long-term health outcomes. Further research is needed to explore the specific impacts of different types and intensities of exercises on this population.

Uremic Toxin Receptor AhR Facilitates Renal Senescence and Fibrosis via Suppressing Mitochondrial Biogenesis.

Retention of metabolic end-products in the bodily fluids of patients with chronic kidney disease (CKD) may lead to uremia. The uremic toxin indoxyl sulfate (IS), a tryptophan metabolite, is an endogenous ligand of aryl hydrocarbon receptor (AhR). It is clarified that the upregulation and activation of AhR by IS in tubular epithelial cells (TECs) promote renal senescence and fibrosis. Renal TEC-specific knockout of AhR attenuates renal senescence and fibrosis, as well as the suppression of PGC1α-mediated mitochondrial biogenesis in ischemia reperfusion (IR)- or IS-treated CKD mice kidneys. Overexpression of peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α) attenuates IS-induced cell senescence and extracellular matrix production in cultured TECs. Mechanistically, AhR is able to interact with PGC1α and promotes the ubiquitin degradation of PGC1α via its E3 ubiquitin ligase activity. In summary, the elevation and activation of AhR by the accumulated uremic toxins in the progression of CKD accelerate renal senescence and fibrosis by suppressing mitochondrial biogenesis via promoting ubiquitination and proteasomal degradation of PGC1α.

Role of Thiamine Supplementation in the Treatment of Chronic Heart Failure: An Updated Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Chronic heart failure (CHF) has always posed a significant threat to human survival and health. The efficacy of thiamine supplementation in CHF patients remains uncertain. HYPOTHESIS: Receiving supplementary thiamine may not confer benefits to patients with CHF. METHODS: A comprehensive search was conducted across the Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov, and Web of Science databases up until May 2023 to identify articles investigating the effects of thiamine supplementation in CHF patients. Predefined criteria were utilized for selecting data on study characteristics and results. RESULTS: Seven randomized, double-blind, controlled trials (five parallel trials and two crossover trials) involving a total of 274 patients were enrolled. The results of the meta-analysis pooling these studies did not reveal any significant effect of thiamine treatment compared with placebo on left ventricular ejection fraction (WMD = 1.653%, 95% CI:  -1.098 to 4.405, p = 0.239, I2 = 61.8%), left ventricular end-diastolic volume (WMD = -6.831 mL, 95% CI:  -26.367 to 12.704, p = 0.493, I2 = 0.0%), 6-min walking test (WMD = 16.526 m, 95% CI:  -36.582 to 69.634, p = 0.542, I2 = 66.3%), N-terminal pro-B type natriuretic peptide (WMD = 258.150 pg/mL, 95% CI:  -236.406 to 752.707, p = 0.306, I2 = 21.6%), or New York Heart Association class (WMD = -0.223, 95% CI:  -0.781 to 0.335, p = 0.434, I2 = 87.1%). However, it effectively improved the status of thiamine deficiency (TD). CONCLUSIONS: Our meta-analysis indicates that thiamine supplementation does not have a direct therapeutic effect on CHF, except for correcting TD.

Transcutaneous auricular vagal nerve stimulation for consciousness recovery in patients with prolonged disorders of consciousness (TAVREC): study protocol for a multicenter, triple-blind, randomized controlled trial in China.

INTRODUCTION: Prolonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve stimulation (taVNS), a safe, non-invasive intervention modulating thalamo-cortical connectivity and brain function, is a possible treatment option of pDoC. We developed a protocol for a randomised controlled study to evaluate the effectiveness of taVNS on consciousness recovery in patients with pDoC (TAVREC). METHODS AND ANALYSIS: The TAVREC programme is a multicentre, triple-blind, randomised controlled trial with 4 weeks intervention followed by 4 weeks follow-up period. A minimum number of 116 eligible pDoC patients will be recruited and randomly receive either: (1) conventional therapy plus taVNS (30 s monophasic square current of pulse width 300 µs, frequency of 25 Hz and intensity of 1 mA followed by 30 s rest, 60 min, two times per day, for 4 weeks); or (2) conventional therapy plus taVNS placebo. Primary outcome of TAVREC is the rate of improved consciousness level based on the Coma Recovery Scale-Revised (CRS-R) at week 4. Secondary outcomes are CRS-R total and subscale scores, Glasgow Coma Scale score, Full Outline of UnResponsiveness score, ECG parameters, brainstem auditory evoked potential, upper somatosensory evoked potential, neuroimaging parameters from positron emission tomography/functional MRI, serum biomarkers associated with consciousness level and adverse events. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (Reference number: 2023-SR-392). Findings will be disseminated in a peer-reviewed journal and presented at relevant conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073950.

Increased incidence of acute primary angle closure during the COVID-19 outbreak in China: A retrospective analysis.

This study aimed to investigate the incidence and clinical characteristics of acute primary angle closure (APAC) during the Coronavirus Disease 2019 (COVID-19) pandemic in China. This was a retrospective study of patients diagnosed with APAC in a glaucoma clinic over a 5-year period. We compared the number of APAC cases during the COVID-19 outbreak (December 7, 2022 to January 7, 2023) with those during the same period in previous years and 2 months prior to the outbreak. We also collected data on the demographic and clinical features of APAC patients, such as age, sex, disease course, visual acuity, intraocular pressure (IOP), and lens opacity. We included 95 eyes of 88 patients with APAC were included. Of these, 65 were female and 23 were male. The mean age was 68.0 ±â€…8.1 years. The median disease course was 10.8 ±â€…9.5 days. There was a significant increase in the number of APAC cases during the COVID-19 outbreak compared with the same months over a 5-year period (44 vs 51, P < .001). A higher proportion of women developed APAC during the outbreak period than during the non-outbreak period (P < .001). Eyes with APAC in the outbreak period had a lower mean IOP than those in the preceding 6 months (40.5 ±â€…8.8 mm Hg vs 46.1 ±â€…10.1 mm Hg; P = .043). No significant differences were observed in disease duration, lens opacity, or bilateral or unilateral onset between the 2 groups. Our study suggests a potential correlation between APAC and COVID-19, marked by a significant surge in APAC cases concurrent with the COVID-19 outbreak. However, the underlying mechanisms and preventive strategies remain to be elucidated.

Association of pulsatility index with total burden of cerebral small vessel disease and cognitive impairment.

OBJECTIVE: This study investigated the correlation between the pulsatility index (PI) of the middle cerebral artery with the total burden of cerebral small vessel disease and cognitive impairment. METHOD: Information on patients hospitalized in the Department of Neurology was collected retrospectively. These patients had complete clinical and laboratory data. The middle cerebral artery PI was measured using transcranial Doppler, a Mini-Mental State Examination (MMSE) was used to assess cognitive function, and the total cerebral small vessel disease burden was assessed using magnetic resonance imaging. Patients were grouped according to their scores for total imaging burden of cerebral small vessel disease and cognitive function. Logistic regression analysis assessed the association between the PI, total imaging burden, and cognitive impairment. Spearman analysis was used to evaluate the correlation between the PI and total imaging burden and cognitive impairment, and receiver operating characteristic (ROC) curves were used to determine the predictive value of the PI for cognitive function. RESULTS: The PI was higher in the cognitive impairment (CI) group than in the no-CI group. Binary logistic regression analysis showed that increased PI was an independent risk factor for CI (OR = 1.582; 95% CI: 1.043-2.401; p = .031) and total imaging burden (OR = 1.842; 95% CI: 1.274-2.663; p = .001). Spearman analysis found that the PI correlated negatively with the MMSE score (r = -.627, p < .001). ROC curve analysis showed the PI predicted CI with an area under the curve of 0.784. The PI combined with the total imaging burden predicted CI in cerebral small vessel disease with an area under the curve of 0.832. CONCLUSION: An increased PI was associated with CI and a high imaging burden in cerebral small vessel disease patients. The PI combined with the total burden score shows a high predictive value for CI.

Landscape of transcriptome-wide m6A modification in diabetic liver reveals rewiring of PI3K-Akt signaling after physical exercise.

AIM: Type 2 diabetes mellitus (T2DM) is one of the most common diseases, and epigenetic modification N6-methyladenosine (m6A) is essential for transcriptional modulation involved in its development. However, the precise role and landscape of transcriptome-wide m6A alterations in molecular adaptations after physical exercise have yet to be fully elucidated. METHODS: Four-week-old male C57BL/6J mice received a high-fat diet (HFD) for 12 weeks to establish a diabetic state, and HFD mice were simultaneously subjected to physical exercise (HFD + EX). The hepatic RNA m6A methylome was examined, the conjoint MeRIP-seq and RNA-seq was performed, and the exercise-modulated genes were confirmed. RESULTS: Physical exercise significantly ameliorates liver metabolic disorder and triggers a dynamic change in hepatic RNA m6A. By analyzing the distribution of m6A in transcriptomes, an abundance of m6A throughout mRNA transcripts and a pattern of conserved m6A after physical exercise was identified. It is noteworthy that conjoint MeRIP-seq and RNA-seq data revealed that both differentially methylated genes and differentially expressed genes were enriched in all stages of the PI3K-Akt signaling pathway, in particular the upstream nodes of this pathway, which are considered a valuable therapeutic target for T2DM. Moreover, in vivo and in vitro analyses showed that exercise-mediated methyltransferase Rbm15 positively regulated the expression of two upstream genes (Itga3 and Fgf21) in an m6A-dependent manner. CONCLUSION: These findings highlight the pivotal role of the exercise-induced m6A epigenetic network and contribute insights into the intricate epigenetic mechanism underlying insulin signaling.

Research on the Vision-Based Dairy Cow Ear Tag Recognition Method.

With the increase in the scale of breeding at modern pastures, the management of dairy cows has become much more challenging, and individual recognition is the key to the implementation of precision farming. Based on the need for low-cost and accurate herd management and for non-stressful and non-invasive individual recognition, we propose a vision-based automatic recognition method for dairy cow ear tags. Firstly, for the detection of cow ear tags, the lightweight Small-YOLOV5s is proposed, and then a differentiable binarization network (DBNet) combined with a convolutional recurrent neural network (CRNN) is used to achieve the recognition of the numbers on ear tags. The experimental results demonstrated notable improvements: Compared to those of YOLOV5s, Small-YOLOV5s enhanced recall by 1.5%, increased the mean average precision by 0.9%, reduced the number of model parameters by 5,447,802, and enhanced the average prediction speed for a single image by 0.5 ms. The final accuracy of the ear tag number recognition was an impressive 92.1%. Moreover, this study introduces two standardized experimental datasets specifically designed for the ear tag detection and recognition of dairy cows. These datasets will be made freely available to researchers in the global dairy cattle community with the intention of fostering intelligent advancements in the breeding industry.

Efficacy of turmeric in the treatment of oral mucositis in patients with head and neck cancer after radiotherapy or chemoradiotherapy: a systematic review and meta-analysis.

Background: Oral mucositis is a major complication for head and neck cancer (HNC) patients after radiotherapy or chemotherapy. A meta-analysis was performed to assess the efficacy of turmeric in the treatment of oral mucositis in HNC patients. Methods: Randomized controlled trials investigating our topic were included in the meta-analysis. The clinical outcomes considered were the severity of oral mucositis, pain level, and weight loss. Results: A total of eight articles that met our inclusion criteria were included in our meta-analysis. At the 3-week follow-up visit, the turmeric group showed significantly lower grades of oral mucositis compared to the control group (p = 0.03). When compared to the placebo group, a significant difference in the degree of oral mucositis was observed at the 4-(p = 0.03) and 6-week (p < 0.00001) follow-up visits. No significant difference in pain levels was observed between the turmeric and control groups at any of the follow-up visits. However, a significant improvement in pain levels for the turmeric group when compared with the placebo group was observed only at the 6-week follow-up visit (p = 0.006). Interestingly, a significant improvement in pain levels was observed for the turmeric group at the 2-, 4-, 5-, and 6-week follow-up visits (p < 0.05) when compared to the non-placebo group. The turmeric group showed less weight loss than the control group at the final follow-up visit (p = 0.03). conclusion: Our meta-analysis showed that using turmeric may be effective in improving both the severity of oral mucositis and pain levels in HNC patients who have received radiotherapy or radiochemotherapy. In addition, the turmeric group experienced less weight loss.

Cow Behavior Recognition Based on Wearable Nose Rings.

This study introduces a novel device designed to monitor dairy cow behavior, with a particular focus on feeding, rumination, and other behaviors. This study investigates the association between the cow behaviors and acceleration data collected using a three-axis, nose-mounted accelerometer, as well as the feasibility of improving the behavioral classification accuracy through machine learning. A total of 11 cows were used. We utilized three-axis acceleration sensors that were fixed to the cow's nose, and these devices provided detailed and unique data corresponding to their activity; in particular, a recorder was installed on each nasal device to obtain acceleration data, which were then used to calculate activity levels and changes. In addition, we visually observed the behavior of the cattle. The characteristic acceleration values during feeding, rumination, and other behavior were recorded; there were significant differences in the activity levels and changes between different behaviors. The results indicated that the nose ring device had the potential to accurately differentiate between eating and rumination behaviors, thus providing an effective method for the early detection of health problems and cattle management. The eating, rumination, and other behaviors of cows were classified with high accuracy using the machine learning technique, which can be used to calculate the activity levels and changes in cattle based on the data obtained from the nose-mounted, three-axis accelerometer.

RPL35A drives ovarian cancer progression by promoting the binding of YY1 to CTCF promoter.

Ovarian cancer is one of the most common gynaecological malignancies with poor prognosis and lack of effective treatment. The improvement of the situation of ovarian cancer urgently requires the exploration of its molecular mechanism to develop more effective molecular targeted drugs. In this study, the role of human ribosomal protein l35a (RPL35A) in ovarian cancer was explored in vitro and in vivo. Our data identified that RPL35A expression was abnormally elevated in ovarian cancer. Clinically, high expression of RPL35A predicted short survival and poor TNM staging in patients with ovarian cancer. Functionally, RPL35A knock down inhibited ovarian cancer cell proliferation and migration, enhanced apoptosis, while overexpression had the opposite effect. Mechanically, RPL35A promoted the direct binding of transcription factor YY1 to CTCF in ovarian cancer cells. Consistently, RPL35A regulated ovarian cancer progression depending on CTCF in vitro and in vivo. Furthermore, RPL35A affected the proliferation and apoptosis of ovarian cancer cells through PPAR signalling pathway. In conclusion, RPL35A drove ovarian cancer progression by promoting the binding of YY1 and CTCF promoter, and inhibiting this process may be an effective strategy for targeted therapy of this disease.

The Synergistic Effect on the Mimetic Optical Structure of Feline Eyes toward Household Health Monitoring of Acute and Chronic Diseases.

A breakthrough in the performance of bionic optical structures will only be achieved if we can obtain an in-depth understanding of the synergy mechanisms operating in natural optical structures and find ways to imitate them. In this work, inspired by feline eyes, an optical substrate that takes advantage of a synergistic effect that occurs between resonant and reflective structures was designed. The synergistic effect between the reflective and resonant components leads to a Raman enhancement factor (EF) of 1.16 × 107, which is much greater than that achieved using the reflective/resonant cavities on their own. Finite-difference time-domain (FDTD) simulations and experimental results together confirm that the mechanism of this synergistic effect is achieved by realizing multiple reflections and repeated absorptions of light, generating a strong local electric field. Thus, a 2-3 order of magnitude increase in sensitivity could be achieved. More importantly, with the homemade centrifugal device, above optical substrates were further used to develop a rapidly highly sensitive household health monitoring system (detection time <3 min). It can thus be used to give early warning of acute diseases with high risk (e.g., acute myocardial infarction (AMI) and cerebral peduncle). Due to the good reusability and storability (9% and 8% reduction in EF after washing 30 times and 9 months of storage, respectively) of the substrates, the substrates thus reduce detection costs (to ∼$1), making them much cheaper to use than the current gold-standard methods (e.g., ∼$16 for gout detection).

Direct observation and measurement of circumlental space and its relation to anterior chamber angle characteristics in iridotomized phakic eyes with primary angle closure disease.

Primary angle closure disease (PACD) is a major cause of blindness worldwide. It has a high prevalence in East Asia, especially in China, which leads to a higher incidence of blindness than open-angle glaucoma. The aim of this study was to directly observe the circumlental space (CLS) in laser peripheral iridotomized eyes with PACD and to determine whether this structure plays a role in the pathogenesis of PACD. Fifty eyes of 50 patients with PACD, who had received laser peripheral iridotomy performed with neodymium:yttrium-aluminum-garnet were recruited from glaucoma clinics from March 2021 to May 2022, including 17 primary angle closure suspect (PACS), 16 primary angle closure (PAC) and 17 primary angle closure glaucoma (PACG). They were classified into two groups based on whether the ciliary process and the crystalline lens equator were in contact using slit-lamp photograph: the attached group and the unattached group. The demographic, clinical characteristics and anterior segment parameters measured from ultrasound biomicroscopy were compared between the attached group and the unattached group. Thirty-three eyes were assigned to the attached group and 17 eyes belonged to the unattached group. In the unattached group, the mean CLS was 0.10 ± 0.07 mm. No significant differences were identified between the different diagnosis groups in age, sex, best-corrected visual acuity, intraocular pressure, white-to-white, axial length, central corneal thickness, anterior chamber depth, flat keratometry, steep keratometry or iridotomy diameter (p > 0.05). The unattached group had shorter trabecular-ciliary process distance (p = 0.021) and larger ciliary process area (p = 0.001) compared with the attached group. Small CLS and its potential effect (partial ciliary block) might be considered as one of the mechanisms of PACD.

Global scientific trends in research of epigenetic response to exercise: A bibliometric analysis.

The purpose of this work is to comprehensively understand the adaptive response of multiple epigenetic modifications on gene expression changes driven by exercise. Here, we retrieved literatures from publications in the PubMed and Web of Science Core Collection databases up to and including October 15, 2023. After screening with the exclusion criteria, 1910 publications were selected in total, comprising 1399 articles and 511 reviews. Specifically, a total of 512, 224, and 772 publications is involved in DNA methylation, histone modification, and noncoding RNAs, respectively. The correlations between publication number, authors, institutions, countries, references, and the characteristics of hotspots were explored by CiteSpace. Here, the USA (621 publications) ranked the world's most-influential countries, the University of California System (68 publications) was the most productive, and Tiago Fernandes (14 publications) had the most-published publications. A comprehensive keyword analysis revealed that cardiovascular disease, cancer, skeletal muscle development, and metabolic syndrome, and are the research hotspots. The detailed impact of exercise was further discussed in different aspects of these three categories of epigenetic modifications. Detailed analysis of epigenetic modifications in response to exercise, including DNA methylation, histone modification, and changes in noncoding RNAs, will offer valuable information to help researchers understand hotspots and emerging trends.

Treatment Preferences and Factors Influencing the Management of Primary Angle-Closure Suspect in China: A National Survey Study.

INTRODUCTION: This study explored the current views of ophthalmologists in China on the preferred strategy and the primary influencing factors in managing primary angle-closure suspect (PACS). METHODS: An online survey was distributed via WeChat to ophthalmologists working in hospitals at all levels throughout China to investigate the optimal management strategy and factors influencing the strategy for treating PACS from February to March 2023. Management strategies examined included regular observation (RO), laser peripheral iridectomy (LPI), and phacoemulsification with intraocular lens implantation (PEI). The study explored the factors that influenced clinical decision-making processes and collected demographic information from the respondents for analysis. RESULTS: A total of 1009 ophthalmologists responded; 442 responders considered RO as a reasonable option for patients with PACS, while the majority opted for more positive treatments, with 460 choosing LPI and 107 selecting PEI. Further grouping analysis revealed significant differences between tertiary and lower-level hospitals (P < 0.01) and between public and private hospitals (P < 0.05). Significant differences were found among resident, attending, and senior doctors and between northern and southern hospitals. The top three considerations for ophthalmologists who selected RO were ultrasound biomicroscopy (UBM) without pupillary block, absence of a family history of glaucoma, and good compliance with regular follow-up. For LPI, the factors were UBM indicating pupillary block, glaucoma symptoms, and poor compliance with regular follow-up. For PEI the factors were age, family history of glaucoma, and poor compliance with regular follow-up. CONCLUSION: The majority of ophthalmologists prefer aggressive treatments such as LPI or PEI over RO when dealing with patients with PACS. Disparity existed among ophthalmologists based on their level of experience, hospital ownership and level, and geographical location. The survey underscores the complexity and multifactorial nature of PACS management and highlights the need for further research and standardization of treatment protocols to ensure optimal patient outcomes.

Neuropsychiatric disorders associated with recreational nitrous oxide use.

BACKGROUND: Recreational nitrous oxide use has grown in popularity among young people and has become a serious public health problem. Chronic use of nitrous oxide can lead to a functional vitamin B12 deficiency and neuropsychiatric complications. PURPOSE: This study aimed to investigate the characteristics of neuropsychiatric complications associated with nitrous oxide use and to enhance clinicians' awareness of this public health problem. METHODS: We retrospectively reviewed 16 patients with neuropsychiatric disorders related to nitrous oxide use who were treated in our hospital from June 2021 to October 2022. Their demographics, clinical features, investigations, treatments and outcomes were analyzed. RESULTS: There were ten males and six females between the ages of 17 and 25 with a mean age of 20.5 ± 2.6 years. Thirteen patients sought medical help from the neurology clinic. Two patients presented to the psychiatric department and one patient presented to the emergency department with acute cognitive impairment. All 16 patients presented with neurological symptoms, such as paresthesia in four limbs or the lower limbs, unsteady gait and weakness. Twelve patients developed psychiatric symptoms, such as hallucinations, agitation, depression, emotional indifference and personality changes. Twelve patients had vitamin B12 deficiency. All 16 patients had hyperhomocysteinemia. Fourteen patients showed abnormal high signal on T2-weighted imaging and an inverted "V" sign in axial view, mainly involving the cervical cord. Neuropsychiatric symptoms improved with vitamin B12 treatment and cessation of nitrous oxide use in all cases. CONCLUSION: Young adults are predominately involved in recreational use of nitrous oxide, which can cause neuropsychiatric complications. The clinical response to vitamin B12 supplementation and cessation of nitrous oxide use is generally good. Clinicians should recognize nitrous oxide use as a public health problem and a cause of a wide range of neuropsychiatric symptoms, particularly in younger patients.

Lightweight Sheep Head Detection and Dynamic Counting Method Based on Neural Network.

To achieve rapid and precise target counting, the quality of target detection serves as a pivotal factor. This study introduces the Sheep's Head-Single Shot MultiBox Detector (SH-SSD) as a solution. Within the network's backbone, the Triple Attention mechanism is incorporated to enhance the MobileNetV3 backbone, resulting in a significant reduction in network parameters and an improvement in detection speed. The network's neck is constructed using a combination of the Spatial Pyramid Pooling module and the Triple Attention Bottleneck module. This combination enhances the extraction of semantic information and the preservation of detailed feature map information, with a slight increase in network parameters. The network's head is established through the Decoupled Head module, optimizing the network's prediction capabilities. Experimental findings demonstrate that the SH-SSD model attains an impressive average detection accuracy of 96.11%, effectively detecting sheep's heads within the sample. Notably, SH-SSD exhibits enhancements across various detection metrics, accompanied by a significant reduction in model parameters. Furthermore, when combined with the DeepSort tracking algorithm, it achieves high-precision quantitative statistics. The SH-SSD model, introduced in this paper, showcases commendable performance in sheep's head detection and offers deployment simplicity, thereby furnishing essential technical support for the advancement of intelligent animal husbandry practices.

Hepatocytic lipocalin-2 controls HDL metabolism and atherosclerosis via Nedd4-1-SR-BI axis in mice.

High-density lipoprotein (HDL) metabolism is regulated by complex interplay between the scavenger receptor group B type 1 (SR-BI) and multiple signaling molecules in the liver. Here, we show that lipocalin-2 (Lcn2) is a key regulator of hepatic SR-BI, HDL metabolism, and atherosclerosis. Overexpression of human Lcn2 in hepatocytes attenuates the development of atherosclerosis via SR-BI in western-diet-fed Ldlr-/- mice, whereas hepatocyte-specific ablation of Lcn2 has the opposite effect. Mechanistically, hepatocyte Lcn2 improves HDL metabolism and alleviates atherogenesis by blocking Nedd4-1-mediated SR-BI ubiquitination at K500 and K508. The Lcn2-improved HDL metabolism is abolished in mice with hepatocyte-specific Nedd4-1 or SR-BI deletion and in SR-BI (K500A/K508A) mutation mice. This study identifies a regulatory axis from Lcn2 to HDL via blocking Nedd4-1-mediated SR-BI ubiquitination and demonstrates that hepatocyte Lcn2 may be a promising target to improve HDL metabolism to treat atherosclerotic cardiovascular diseases.

Proximal Tubular Lats2 Ablation Exacerbates Ischemia/Reperfusion Injury (IRI)-Induced Renal Maladaptive Repair through the Upregulation of P53.

The Hippo pathway mediates renal maladaptive repair after acute kidney injury (AKI), which has been considered a driving force in the progression to chronic kidney disease (CKD). LATS2, a core kinase of the Hippo pathway, exerts non-Hippo-dependent functions in the regulation of the cell cycle and cell fate, providing new insights into AKI and further repair. However, its role remains unknown. Here, we utilized a proximal tubular Lats2 conditional knockout mouse strain (Lats2-CKO) to evaluate the effect of LATS2 deficiency on ischemia/reperfusion-induced AKI-to-CKD transition. Lats2-CKO mice presented with more severe tubular maladaptive repair, inflammatory infiltration, interstitial fibrosis, and apoptosis following AKI. Importantly, we discovered that Lats2 ablation caused the activation of p53, with increased levels of cellular apoptotic molecules (p21, Bax, and cleaved caspase-3), and decreased levels of anti-apoptotic molecules (Bcl-2 and Bcl-xL). Pifithirin-α (p53 inhibitor) effectively attenuated renal fibrosis, inflammation, and apoptosis in Lats2-CKO mice after AKI. Consistently, in vitro Lats2 overexpression decreased p53, p21, Bax and cleaved caspase 3 expression after hypoxia/reoxygenation (H/R) treatment. Of note, the phosphorylation of MDM2, which promotes the ubiquitination degradation of p53, at site Ser186 was decreased in Lats2-CKO kidneys, but increased by Lats2 overexpression in vitro. Therefore, LATS2 deficiency aggravated ischemia/reperfusion injury (IRI)-induced maladaptive repair via regulating the tubular MDM2-p53 axis in AKI-to-CKD transition.