The Clinical Significance and Expression Level of miR-411-5p in Colorectal Cancer.

Background: MicroRNAs (miRNAs) have been widely recognized as crucial regulators in the development and progression of various cancers, including colorectal cancer (CRC). Previous studies have highlighted the involvement of several miRNAs in CRC, such as miR-145, miR-29a-3p, and miR-196. However, the specific role and clinical significance of miR-411-5p in CRC have not been thoroughly investigated, representing a significant gap in the current understanding of CRC biology. While miR-411-5p has been implicated in the pathogenesis of other human malignancies, its precise mechanisms and impact on CRC development and prognosis remain largely unexplored. Understanding the functional relevance of miR-411-5p in CRC and elucidating its molecular interactions can provide valuable insights into the underlying mechanisms of CRC progression and potentially identify novel therapeutic targets. Therefore, this study aims to investigate the clinical value and level of miR-411-5p in colorectal cancer, shedding light on its potential as a diagnostic and prognostic biomarker. Additionally, we aim to explore the molecular mechanisms underlying the effects of miR-411-5p on CRC cells, particularly its interaction with the target gene NFE2L3. By filling this knowledge gap, our research contributes to a deeper understanding of the role of miR-411-5p in CRC and opens avenues for developing targeted therapies for this prevalent malignancy. Methods: Colorectal cancer (CRC) tissue samples and corresponding normal paracancerous tissue samples were collected from 60 CRC patients treated at the Affiliated Hospital of Hebei University. Normal paracancerous tissue refers to the healthy tissue adjacent to the cancerous region. These tissue samples were obtained through biopsies, and the patients provided informed consent for their use in the study. To investigate the expression levels of miR-411-5p and NFE2L3, we employed quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. This technique allowed us to measure the levels of miR-411-5p and NFE2L3 mRNA in both CRC and normal tissue samples. Additionally, we validated the protein levels of NFE2L3 using Western blot analysis. Furthermore, we assessed the functional impact of miR-411-5p on CRC cells through various assays. The MTT assay determined cell viability, the transwell migration assay evaluated cell migration and invasion abilities, and flow cytometry measured the rate of apoptosis in CRC cells. To confirm the molecular interaction between miR-411-5p and its target gene NFE2L3, we conducted dual-luciferase reporter assays. These assays enabled us to validate the binding between miR-411-5p and the 3' untranslated region (3'UTR) of the NFE2L3 mRNA. To investigate the potential therapeutic role of NFE2L3 in CRC, we transfected CRC cells with pcDNA3.0-NFE2L3, a plasmid overexpressing NFE2L3. This allowed us to assess the impact of NFE2L3 restoration on the behavior of CRC cells. Results: Overexpression of miR-411-5p in CRC cells significantly reduced cell viability, inhibited migration and invasion, and increased the rate of apoptosis. Conversely, inhibition of miR-411-5p expression exerted the opposite effects on the biological behavior of CRC cells. Furthermore, our study revealed that NFE2L3 is a downstream target of miR-411-5p. Dual-luciferase reporter assays confirmed the binding between miR-411-5p and the 3'UTR of NFE2L3 mRNA, indicating a direct interaction between them. To investigate the therapeutic potential of targeting NFE2L3 in CRC, we transfected CRC cells with pcDNA3.0-NFE2L3, resulting in the restoration of NFE2L3 levels. This restoration effectively reversed the effects induced by miR-411-5p mimics on the behavior of CRC cells. Conclusion: Our study provides compelling evidence for the tumor-suppressive role of miR-411-5p in CRC. The overexpression of miR-411-5p resulted in reduced cell viability, inhibited migration and invasion, and increased apoptosis in CRC cells. Importantly, we identified NFE2L3 as a downstream target of miR-411-5p and demonstrated its involvement in mediating the effects of miR-411-5p on CRC cell behavior. These findings not only confirm the tumor-suppressive role of miR-411-5p in CRC but also highlight NFE2L3 as a promising target for novel therapeutic strategies. Targeting NFE2L3 to modulate the biological function of CRC cells may hold therapeutic potential and serve as a basis for the development of targeted drugs. Further investigations are warranted to fully elucidate the underlying molecular mechanisms of miR-411-5p-NFE2L3 interaction and its impact on CRC progression. Additionally, future studies could explore the clinical implications of miR-411-5p as a diagnostic or prognostic biomarker in CRC patients. By advancing our understanding of the intricate regulatory networks involved in CRC, we can pave the way for personalized therapeutic approaches and improve patient outcomes.

Rosmarinic acid-grafted gelatin nanogels for efficient diquafosol delivery in dry eye disease therapy.

Dry eye disease (DED) is a prevalent ocular disorder characterized by unstable tear film condition with loss of aqueous or mucin, excessive oxidative stress, and inflammation, leading to discomfort and potential damage to the ocular surface. Current DED therapies have shown restricted therapeutic effects such as frequent dosing and temporary relief with potential unwanted side effects, urgently necessitating the development of innovative efficient therapeutic approaches. Herein, we developed rosmarinic acid (RosA) conjugated gelatin nanogels loading diquafosol sodium (DQS), DRGNG, for simultaneous ROS-scavenging and mucin-secreting DED treatment. Mechanically, DRGNG suppressed the ROS production, reduced inflammatory factors, and prompted mucin secretion in vitro and in vivo. The whole transcriptome RNA sequencing in vitro further provided a detailed analysis of the upregulation of anti-oxidant, anti-inflammatory, and mucin-promotion pathways. Therapeutically, both in evaporative DED and aqueous deficient DED models, the dual-functional DRGNG could prolong the retention time at the ocular surface, efficiently suppress the oxidative stress response, reverse ocular surface morphology, and recover tear film homeostasis, thus alleviating the DED when the dosage is halved compared to the commercial Diquas®. Our findings contribute to developing innovative therapies for DED and offer insights into the broader applications of nanogels in ocular drug delivery and oxidative stress-related conditions.

The Effects of Breastfeeding on Childhood Behavioral and Emotional Development: A Prospective Cohort Study in China.

BACKGROUND: Breastfeeding could improve a child's health early on, but its long-term effects on childhood behavioral and emotional development remain inconclusive. We aimed to estimate the associations of feeding practice with childhood behavioral and emotional development. METHODS: In this population-based birth cohort study, data on feeding patterns for the first 6 mo of life, the duration of breastfeeding, and children's emotional and behavioral outcomes were prospectively collected from 2489 mother-child dyads. Feeding patterns for the first 6 mo included exclusive breastfeeding (EBF) and non-exclusive breastfeeding (non-EBF, including mixed feeding or formula feeding), and the duration of breastfeeding (EBF or mixed feeding) was categorized into ≤6 mo, 7-12 mo, 13-18 mo, and >18 mo. Externalizing problems and internalizing problems were assessed with the Child Behavior Checklist (CBCL) and operationalized according to recommended clinical cutoffs, corresponding to T scores ≥64. Multivariable linear regression and logistic regression were used to evaluate the association of feeding practice with CBCL outcomes. RESULTS: The median (interquartile range) age of children at the outcome measurement was 32.0 (17.0) mo. Compared with non-EBF for the first 6 mo, EBF was associated with a lower T score of internalizing problems [adjusted mean difference (aMD): -1.31; 95% confidence interval (95% CI): -2.53, -0.10], and it was marginally associated with T scores of externalizing problems (aMD: -0.88; 95% CI: -1.92, 0.15). When dichotomized, EBF versus non-EBF was associated with a lower risk of externalizing problems (aOR: 0.54, 95% CI: 0.34, 0.87), and it was marginally associated with internalizing problems (aOR: 0.75, 95% CI: 0.54, 1.06). Regarding the duration of breastfeeding, breastfeeding for 13-18 mo versus ≤6 mo was associated with lower T scores of internalizing problems (aMD: -2.50; 95% CI: -4.43, -0.56) and externalizing problems (aMD: -2.75; 95% CI: -4.40, -1.10), and breastfeeding for >18 mo versus ≤6 mo was associated with lower T scores of externalizing problems (aMD: -1.88; 95% CI: -3.68, -0.08). When dichotomized, breastfeeding for periods of 7-12 mo, 13-18 mo, and >18 mo was associated with lower risks of externalizing problems [aOR (95% CI): 0.96 (0.92, 0.99), 0.94 (0.91, 0.98), 0.96 (0.92, 0.99), respectively]. CONCLUSIONS: Exclusive breastfeeding for the first 6 mo and a longer duration of breastfeeding, exclusively or partially, are beneficial for childhood behavioral and emotional development.

Ultrasensitive plasma-based monitoring of tumor burden using machine-learning-guided signal enrichment.

In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole-genome sequencing (WGS). Here we now introduce MRD-EDGE, a machine-learning-guided WGS ctDNA single-nucleotide variant (SNV) and copy-number variant (CNV) detection platform designed to increase signal enrichment. MRD-EDGESNV uses deep learning and a ctDNA-specific feature space to increase SNV signal-to-noise enrichment in WGS by ~300× compared to previous WGS error suppression. MRD-EDGECNV also reduces the degree of aneuploidy needed for ultrasensitive CNV detection through WGS from 1 Gb to 200 Mb, vastly expanding its applicability within solid tumors. We harness the improved performance to identify MRD following surgery in multiple cancer types, track changes in TF in response to neoadjuvant immunotherapy in lung cancer and demonstrate ctDNA shedding in precancerous colorectal adenomas. Finally, the radical signal-to-noise enrichment in MRD-EDGESNV enables plasma-only (non-tumor-informed) disease monitoring in advanced melanoma and lung cancer, yielding clinically informative TF monitoring for patients on immune-checkpoint inhibition.

Developing a conceptual partner selection framework for matching public-private partnerships of rural energy internet project using an integrated fuzzy AHP approach for rural revitalization in China.

The development of rural clean energy is the key to cope with the shortage of traditional energy supply in the rural revitalization strategy and improve the sustainability of rural energy supply. Under the background of digital age, the development and utilization of rural clean energy Internet has become the focus of rural economic development. The government partners of the Rural clean Energy Internet PPP project (RCEIPPPP) are the key to promoting the green and intelligent development of rural energy. In this paper, the index system of project partner selection is constructed, and the problem of government partner selection for RCEIPPPP is studied by AHP and fuzzy comprehensive evaluation. The results of this study are as follows: 1) Partners' financial ability, technical ability, management ability, performance experience, corporate reputation, cooperation ability and risk management are the influencing factors for government partner selection of rural clean energy Internet PPP projects (RCEIPPPPs); 2) Compared with other factors, financial ability, technical ability, management ability and performance experience are the four key factors that are more important in choosing partners; 3) The empirical research shows that AHP, fuzzy comprehensive evaluation and the index system constructed by this research can be applied to the practice of government partner selection for RCEIPPPPs. This study puts forward the evaluation system of government cooperation selection of energy Internet PPP projects from the theoretical level, improves the existing research methods, and makes the theoretical system in this field more complete. From the practical level, it provides scientific basis and suggestions for the government to make decisions on energy Internet PPP projects, and improves the engineering efficiency and quality of rural clean energy Internet construction. This study demonstrates the complexity of clean energy projects, the need for an integrated approach to decision-making, and the need for project managers to actively manage communication and collaboration with partners to ensure successful project implementation.

Identification and Pharmacological Targeting of Treatment-Resistant, Stem-like Breast Cancer Cells for Combination Therapy.

Tumors frequently harbor isogenic yet epigenetically distinct subpopulations of multi-potent cells with high tumor-initiating potential-often called Cancer Stem-Like Cells (CSLCs). These can display preferential resistance to standard-of-care chemotherapy. Single-cell analyses can help elucidate Master Regulator (MR) proteins responsible for governing the transcriptional state of these cells, thus revealing complementary dependencies that may be leveraged via combination therapy. Interrogation of single-cell RNA sequencing profiles from seven metastatic breast cancer patients, using perturbational profiles of clinically relevant drugs, identified drugs predicted to invert the activity of MR proteins governing the transcriptional state of chemoresistant CSLCs, which were then validated by CROP-seq assays. The top drug, the anthelmintic albendazole, depleted this subpopulation in vivo without noticeable cytotoxicity. Moreover, sequential cycles of albendazole and paclitaxel-a commonly used chemotherapeutic -displayed significant synergy in a patient-derived xenograft (PDX) from a TNBC patient, suggesting that network-based approaches can help develop mechanism-based combinatorial therapies targeting complementary subpopulations.

Exposure to polycyclic aromatic hydrocarbons promotes the progression of low-grade cervical intraepithelial neoplasia: A population-based cohort study in China.

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.

Vaginal micro-environment disorder promotes malignant prognosis of low-grade cervical intraepithelial neoplasia: a prospective community cohort study in Shanxi Province, China.

PURPOSE: Emerging evidence suggests that vaginal micro-environment disorder is closely related to the development of cervical lesions. Low-grade cervical intraepithelial neoplasia (CIN1), as an early stage of cervical lesions, exhibits a high risk of progressing to high-grade lesions or even cervical cancer. However, the effect of vaginal micro-environment on the malignant prognosis of CIN1 remains uncertain. METHODS: A total of 504 patients diagnosed with CIN1 by pathology, who were from the population-based cohorts established in Shanxi Province, China, were enrolled and followed up for 2 years. Micro-environmental factors such as vaginal pH, cleanliness, hydrogen peroxide (H2O2), ß-glucuronidase (GUSB), leucocyte esterase (LE), and sialidase (SNA) were detected to evaluate their effect on the malignant prognosis of CIN1. RESULTS: Abnormal vaginal pH (HR = 1.472, 95%CI 1.071-2.022), cleanliness (HR = 1.446, 95%CI 1.067-1.960), H2O2 (HR = 1.525, 95%CI 1.155-2.013), GUSB (HR = 1.739, 95%CI 1.235-2.448), LE (HR = 1.434, 95%CI 1.038-1.981), and SNA (HR = 1.411, 95%CI 1.065-1.870) could promote a higher incidence of CIN1 malignant prognosis, and the combined effects of these micro-environmental factors resulted in a nearly twofold increased risk (HR = 2.492, 95%CI 1.773-3.504) compared to any single factor alone, especially under the high-risk human papillomavirus (HR-HPV) infection. Notably, the cumulative incidence of malignant prognosis for CIN1 gradually increased during the early follow-up period, reaching its peak at approximately 8 months, and then stabilizing. CONCLUSION: Vaginal micro-environment disorder could promote CIN1 malignant prognosis, particularly in HR-HPV-infected women. Taking micro-environmental factors as the breakthrough, our study provides a feasible vision for preventing early stage cervical lesions.

Postoperative delayed massive bleeding in gastric cancer: a case report.

BACKGROUND: Postoperative delayed bleeding of gastric cancer is a complication of radical gastrectomy with low incidence rate and high mortality. CASE PRESENTATION: This case report presents the case of a 63-year-old female patient of Mongolian ethnicity who was diagnosed with gastric malignancy during a routine medical examination and underwent Billroth's I gastric resection in our department. However, on the 24th day after the surgery, she was readmitted due to sudden onset of hematemesis. Gastroscopy, abdominal CT, and digital subtraction angiography revealed postoperative anastomotic fistula, rupture of the duodenal artery, and bleeding from the abdominal aorta. The patient underwent three surgical interventions and two arterial embolizations. The patient's condition stabilized, and she was discharged successfully. CONCLUSION: Currently, there are no specific guidelines for the diagnosis and treatment of pseudoaneurysms in the abdominal cavity resulting from gastric cancer surgery. Early digital subtraction angiography examination should be performed to assist in formulating treatment plans. Early diagnosis and treatment contribute to an improved overall success rate of rescue interventions.

Ultrahigh-reflective optical thin films prepared by reactive magnetron sputtering with RF-induced substrate bias.

Optical thin films with high-reflectivity (HR) are essential for applications in quantum precision measurements. In this work, we propose a coating technique based on reactive magnetron sputtering with RF-induced substrate bias to fabricate HR-optical thin films. First, atomically flat SiO2 and Ta2O5 layers have been demonstrated due to the assistance of radio-frequency plasma during the coating process. Second, a distributed Bragg reflector (DBR) mirror with an HR of ∼99.999 328% centered at 1397 nm has been realized. The DBR structure is air-H{LH}19-substrate, in which the L and H denote a single layer of SiO2 with a thickness of 237.8 nm and a single layer of Ta2O5 with a thickness of 171.6 nm, respectively. This novel coating method would facilitate the development of HR reflectors and promote their wide applications in precision measurements.

Impact of cesarean section on metabolic syndrome components in offspring rats.

INTRODUCTION: Epidemiological evidence suggests an association between CS and offspring metabolic syndrome (MetS), but whether a causal relationship exists is unknown. METHODS: In this study, timed-mated Wistar rat dams were randomly assigned to cesarean section (CS), vaginal delivery (VD), and surrogate groups. The offspring from both CS and VD groups were reared by surrogate dams until weaning, and weaned male offspring from both groups were randomly assigned to receive normal diet (ND) or high-fat/high-fructose diet (HFF) ad libitum for 39 weeks. RESULTS: By the end of study, CS-ND offspring gained 17.8% more weight than VD-ND offspring, while CS-HFF offspring gained 36.4% more weight than VD-HFF offspring. Compared with VD-ND offspring, CS-ND offspring tended to have increased triglycerides (0.27 mmol/l, 95% CI, 0.05 to 0.50), total cholesterol (0.30 mmol/l, -0.08 to 0.68), and fasting plasma glucose (FPG) (0.30 mmol/l, -0.01 to 0.60); more pronounced differences were observed between CS-HFF and VD-HFF offspring in these indicators (triglyceride, 0.66 mmol/l, 0.35 to 0.97; total cholesterol, 0.46 mmol/l, 0.13 to 0.79; and FPG, 0.55 mmol/l, 0.13 to 0.98). CONCLUSIONS: CS offspring were more prone to adverse metabolic profile and HFF might exacerbate this condition, indicating the association between CS and MetS is likely to be causal. IMPACT: Whether the observed associations between CS and MetS in non-randomized human studies are causally relevant remains undetermined. Compared with vaginally born offspring rats, CS born offspring gained more body weight and tended to have compromised lipid profiles and abnormal insulin sensitivity, suggesting a causal relationship between CS and MetS that may be further amplified by a high-fat/high-fructose diet. Due to the high prevalence of CS births globally, greater clinical consideration must be given to the potential adverse effects of CS, and whether these risks should be made known to patients in clinical practice merits evaluation.

PM2.5 induces cardiac defects via AHR-SIRT1-PGC-1α mediated mitochondrial damage.

Recent evidence indicates that PM2.5 poses a risk for congenital heart diseases, but the mechanisms remain unclear. We hypothesized that AHR activated by PM2.5 might cause mitochondrial damage via PGC-1α dysregulation, leading to heart defects. We initially discovered that the PGC-1α activator ZLN005 counteracted cardiac defects in zebrafish larvae exposed to EOM (extractable organic matter) from PM2.5. Moreover, ZLN005 attenuated EOM-induced PGC-1α downregulation, mitochondrial dysfunction/biogenesis, and apoptosis. EOM exposure not only decreased PGC-1α expression levels, but suppressed its activity via deacetylation, and SIRT1 activity is required during both processes. We then found that SIRT1 expression levels and NAD+/NADH ratio were reduced in an AHR-dependent way. We also demonstrated that AHR directly suppressed the transcription of SIRT1 while promoted the transcription of TiPARP which consumed NAD+. In conclusion, our study suggests that PM2.5 induces mitochondrial damage and heart defects via AHR/SIRT1/PGC-1α signal pathway.

AHR/cyp1b1 signaling-mediated extrinsic apoptosis contributes to 6PPDQ-induced cardiac dysfunction in zebrafish embryos.

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPDQ) has raised significant concerns due to its widespread distribution and high toxicity to aquatic organisms. However, the cardiac developmental toxicity of 6PPDQ and the underlying mechanisms remain unclear. In this study, we observed no notable alterations in heart morphology or embryo survival in zebrafish embryos exposed to 6PPDQ (0.2-2000 µg/L) up to 3 days post-fertilization (dpf). However, concentrations at 2 µg/L or higher induced cardiac dysfunctions, leading to lethal effects at later stages (6-8 dpf). We further found that the aryl hydrocarbon receptor (AHR) inhibitor CH22351 attenuated 6PPDQ-induced cardiac dysfunctions, implicating the involvement of AHR signal pathway. Moreover, 6PPDQ exposure led to an overproduction of reactive oxygen species (ROS) and an upregulation of genes associated with oxidative stress (sod1, sod2, and nrf2a). This was accompanied by an increase in oxidative DNA damage and the induction of p53-dependent extrinsic apoptosis. Co-exposure to the ROS scavenger N-acetylcysteine effectively counteracted the DNA damage and apoptosis induced by 6PPDQ. Importantly, inhibition of AHR or its downstream target cyp1b1 attenuated 6PPDQ-induced oxidative stress, DNA damage, and apoptosis. In conclusion, our results provide evidence that 6PPDQ induces oxidative stress through the AHR/cyp1b1 signaling pathway, leading to DNA damage and extrinsic apoptosis, ultimately resulting in cardiac dysfunction.

Efficient adsorption of phosphorus by macroscopic MOF/chitosan composites and preliminary investigation of subsequent phosphorus recovery through electrochemically-driven struvite precipitation.

The proper management of phosphorus (P) from wastewater is crucial for sustainable development consideration. Herein, we developed a strategy which combines adsorption via tailored adsorbents and electrochemically-driven struvite precipitation (ESP) for P recovery. Novel polydopamine-modified Ce-MOF/chitosan composite beads (PDA@Ce-MOF-CS) were prepared by a facile in situ growth of Ce-MOF crystals incorporated natural polymers and PDA coating. The physicochemical properties of PDA@Ce-MOF-CS were characterized. Both batch and fixed-bed column experiments were conducted to evaluate its adsorption performances. Representatively, PDA@Ce-MOF-CS performed good selectivity for P removal and exhibited a maximum adsorption capacity of 161.13 mg P/g at pH 3 and 318 K. Meanwhile, the developed adsorbent showed great reusability after ten regeneration cycles as well as good adsorption stability. The dominant mechanism for efficient P adsorption included electrostatic attraction, surface precipitation and ligand exchange. Interestingly, PDA@Ce-MOF-CS exhibited a remarkable adsorption capacity of 92.86 mg P/g by treating real P-rich electroplating wastewater, and the desorbed P in the eluate could be effectively recovered and converted into a solid fertilizer as struvite via ESP. Overall, this work provided a new research direction for P recovery from wastewater as struvite by combined technologies with the help of macroscopic MOF architectures.

Transformer-based light-evoked retinal spiking activity prediction.

Retinal visual prosthetic devices aim to restore vision via electrical stimulation delivered on the retina. While a number of devices have been commercially available, the stimulation strategies applied have not met the expectations of end-users. These stimulation strategies involve the neurons being activated based on their spatial properties, regardless of their functions, which may lead to lower visual acuity. The ability to predict light-evoked neural activities thus becomes crucial for the development of a retinal prosthetic device with better visual acuity. In addition to temporal nonlinearity, the spatial relationship between the 2-dimensional light stimulus and the spiking activity of neuron populations is the main barrier to accurate predictions. Recent advances in deep learning offer a possible alternative for neural activity prediction tasks. With proven performance on nonlinear sequential data in fields such as natural language processing and computer vision, the emerging transformer model may be adapted to predict neural activities. In this study, we built and evaluated a deep learning model based on the transformer to explore its predictive capacity in light-evoked retinal spikes. Our preliminary results show that the model is possible to achieve good performance in this task. The high versatility of deep learning models may allow us to make retinal activity predictions in more complex physiological environments and potentially enhance the visual acuity of retinal prosthetic devices in the future by enabling us to anticipate the desired neural responses to electrical stimuli.

Cross-View Gait Recognition Method Based on Multi-Teacher Joint Knowledge Distillation.

Aiming at challenges such as the high complexity of the network model, the large number of parameters, and the slow speed of training and testing in cross-view gait recognition, this paper proposes a solution: Multi-teacher Joint Knowledge Distillation (MJKD). The algorithm employs multiple complex teacher models to train gait images from a single view, extracting inter-class relationships that are then weighted and integrated into the set of inter-class relationships. These relationships guide the training of a lightweight student model, improving its gait feature extraction capability and recognition accuracy. To validate the effectiveness of the proposed Multi-teacher Joint Knowledge Distillation (MJKD), the paper performs experiments on the CASIA_B dataset using the ResNet network as the benchmark. The experimental results show that the student model trained by Multi-teacher Joint Knowledge Distillation (MJKD) achieves 98.24% recognition accuracy while significantly reducing the number of parameters and computational cost.

Acute flare of systemic lupus erythematosus with extensive gastrointestinal involvement: A case report and review of literature.

BACKGROUND: Lupus mesenteric vasculitis (LMV) is a serious condition that may occur as an acute manifestation of gastrointestinal (GI) involvement and is not easily diagnosed by physicians. Delayed diagnosis and treatment of LMV may lead to rapid disease progression and can be life threatening. CASE SUMMARY: A previously healthy 27-year-old woman presented with abdominal pain following a history of fatigue and consumption of cold water. Laboratory investigations, physical examinations, and enhanced abdominal computed tomography (CT) suggested systemic lupus erythematosus complicated by LMV. She received treatments, such as GI decompression, somatostatin, glucocorticoids, and immunosuppressants, and was evaluated using color ultrasonography. Twenty days later, the patient reported no stomach discomfort and was able to consume semi-liquid food. Laboratory investigations showed that inflammatory factors decreased to normal levels and complement levels increased slightly. One year after discharged, she recovered with methylprednisolone being tapered to 4 mg per day, mycophenolate mofetil to 0.75 g bid, and hydroxychloroquine to 0.2 g bid; however, only C3 complement level was slightly below the normal level. CONCLUSION: Early diagnosis of LMV is essential for successful treatment; this depends on a combination of clinical manifestations, laboratory investigations, and imaging findings. Enhanced CT is preferred, but ultrasonography can be used for prompt screening and follow-up.

A Doped Lanthanide-Based Coordination Polymer Exhibiting High Relative Sensitivity to Ratiometric Luminescent Thermometers at 440 K.

Ratiometric luminescent thermometers with excellent performance often require the luminescent materials to possess high thermal stability and relative sensitivity (Sr). However, such luminescent materials are very rare, especially in physiological (298-323 K) and high-temperature (>373 K) regions. Here we report the synthesis and luminescent property of [Tb0.995Eu0.005(pfbz)2(phen)Cl] (3), which not only exhibits high Sr in physiological temperature but also has a Sr up to 7.47% K-1 at 440 K, the largest Sr at 440 K in known lanthanide-based coordination compound luminescent materials.

Cervicovaginal microbiota disorder combined with the change of cytosine phosphate guanine motif- toll like receptor 9 axis was associated with cervical cancerization.

BACKGROUND: Convincing studies demonstrated that cervicovaginal microbiota disorder and toll-like receptor 9 (TLR9) high expression were related to cervical carcinogenesis. However, the effects of cervicovaginal microbiota integration TLR9 in cervical cancerization are unclear. Based on the biological basis that unmethylated cytosine-phosphate-guanine (CpG) motifs of bacteria could activate TLR9, we explored the effects of cervicovaginal microbiota disorder and CpG motif-TLR9 axis change in cervical carcinogenesis. METHODS: A total of 341 participants, including 124 normal cervical (NC), 90 low-grade cervical intraepithelial neoplasia (CIN1), 78 high-grade cervical intraepithelial neoplasia (CIN2/3) and 49 squamous cervical cancer (SCC), diagnosed by pathology were enrolled in the study. Here, metagenomic shotgun sequencing was used to reveal cervicovaginal microbiota characteristics, and TLR9 protein was detected by western blotting. RESULTS: Our results showed that the diversity of cervicovaginal microbiota gradually increased along with the poor development of cervical lesions, showing the abundance of Lactobacillus crispatus and Lactobacillus iners decreased, while the abundance of pathogenic bacteria gradually increased. The level of TLR9 expression was gradually increased with cervicovaginal microbiota diversity increasing, the abundance of Lactobacillus decreasing, and we found a positive correlation dependency relationship (r = 0.384, P = 0.002) between TLR9 and GTCGTT motif content. Stratified analysis based on HPV16 infection, we found that the characteristics of cervicovaginal microbiota and increased TLR9 expression were also closely related to HPV16 infection. CONCLUSIONS: Cervicovaginal microbiota dysbiosis might lead to the CpG motif increased, which was closely associated with TLR9 high expression, and ultimately might promote the progression of cervical lesions.

KLRG1 marks tumor-infiltrating CD4 T cell subsets associated with tumor progression and immunotherapy response.

Current methods for biomarker discovery and target identification in immuno-oncology rely on static snapshots of tumor immunity. To thoroughly characterize the temporal nature of antitumor immune responses, we developed a 34-parameter spectral flow cytometry panel and performed high-throughput analyses in critical contexts. We leveraged two distinct preclinical models that recapitulate cancer immunoediting (NPK-C1) and immune checkpoint blockade (ICB) response (MC38), respectively, and profiled multiple relevant tissues at and around key inflection points of immune surveillance and escape and/or ICB response. Machine learning-driven data analysis revealed a pattern of KLRG1 expression that uniquely identified intratumoral effector CD4 T cell populations that constitutively associate with tumor burden across tumor models, and are lost in tumors undergoing regression in response to ICB. Similarly, a Helios-KLRG1+ subset of tumor-infiltrating regulatory T cells was associated with tumor progression from immune equilibrium to escape and was also lost in tumors responding to ICB. Validation studies confirmed KLRG1 signatures in human tumor-infiltrating CD4 T cells associate with disease progression in renal cancer. These findings nominate KLRG1+ CD4 T cell populations as subsets for further investigation in cancer immunity and demonstrate the utility of longitudinal spectral flow profiling as an engine of dynamic biomarker discovery.