Isoquercitrin alleviates pirarubicin-induced cardiotoxicity in vivo and in vitro by inhibiting apoptosis through Phlpp1/AKT/Bcl-2 signaling pathway.

Introduction: Due to the cardiotoxicity of pirarubicin (THP), it is necessary to investigate new compounds for the treatment of THP-induced cardiotoxicity. Isoquercitrin (IQC) is a natural flavonoid with anti-oxidant and anti-apoptosis properties. Thus, the present study aimed to investigate the influence of IQC on preventing the THP-induced cardiotoxicity in vivo and in vitro. Methods: The optimal concentration and time required for IQC to prevent THP-induced cardiomyocyte damage were determined by an MTT assay. The protective effect was further verified in H9c2 and HCM cells using dichlorodihydrofluorescein diacetate fluorescent probes, MitoTracker Red probe, enzyme-linked immunosorbent assay, JC-1 probe, and real time-quantitative polymerase chain reaction (RT-qPCR). Rats were administered THP to establish cardiotoxicity. An electrocardiogram (ECG) was performed, and cardiac hemodynamics, myocardial enzymes, oxidative stress indicators, and hematoxylin-eosin staining were studied. Voltage-dependent anion channel 1 (VDAC1), adenine nucleotide translocase 1 (ANT1), and cyclophilin D (CYPD) were detected by qRT-PCR, and the Phlpp1/AKT/Bcl-2 axis proteins were detected by western blot, confirming that IQC markedly increased cell viability and superoxide dismutase (SOD) levels, diminished the levels of ROS and MDA, and elevated mitochondrial function and apoptosis in vivo and in vitro. Results: Results showed that IQC reduced THP-induced myocardial histopathological injury, electrocardiogram (ECG) abnormalities, and cardiac dysfunction in vivo. IQC also decreased serum levels of MDA, BNP, CK-MB, c-TnT, and LDH, while increasing levels of SOD and GSH. We also found that IQC significantly reduced VDAC1, ANT1, and CYPD mRNA expression. In addition, IQC controlled apoptosis by modulating Phlpp1/AKT/Bcl-2 signaling pathways. IQC markedly increased H9c2 and HCM cell viability and SOD levels, diminished the levels of ROS and MDA, and elevated mitochondrial function in H9c2 and HCM cells to defend against THP-induced cardiomyocyte apoptosis in vitro. The AKT inhibitor IMQ demonstrated that IQC lacked antioxidant and anti-apoptotic properties. Moreover, our data showed that IQC regulates Phlpp1 expression, thereby influencing the expression levels of p-AKT, cytochrome c, caspase-3, caspase-9, Bcl-2, and Bax. Discussion: In conclusion, our results indicate that IQC protects the changes in mitochondrial membrane permeability in cardiomyocytes by regulating the Phlpp1/AKT/Bcl-2 signaling pathway, inhibits the release of cytc from the mitochondrial inner membrane to the cytoplasm, forms apoptotic bodies, induces cell apoptosis, and reduces THP induced cardiotoxicity.

Dietary tryptophan improves growth and intestinal health by promoting the secretion of intestinal ß-defensins against enterotoxigenic E. coli F4 in weaned piglets.

Adequate dietary L-tryptophan (Trp) governs intestinal homeostasis in piglets. However, the defensive role of Trp in the diet against enterotoxigenic E. coli F4 (K88) in pigs is still poorly understood. Here, sixty (6.15 ± 1.52 kg, 24-day-old, Duroc × Landrace × Yorkshire) weaned piglets were used for an E. coli F4 attack test in a 2 × 2 factorial design. The growth (ADG, ADFI, GH), immune factors (IL-10, IgA, IgG, IgM), Trp metabolite 5-HT, intestinal morphology (jejunal and colonic VH), mRNA expression of ß-defensins (jejunal BD-127, BD-119, ileal BD-1, BD-127), and abundance of beneficial microorganisms in the colon (Prevotella 9, Lactobacillus, Phascolarctobacterium, Faecalibacterium) were higher in the piglets in the HT (High Trp) and HTK (High Trp, K88) groups than in the LT (Low Trp) and LTK (Low Trp, K88) groups (P < 0.05), while FCR, diarrhea rate, diarrhea index, serum Trp, Kyn, IDO, D-LA, ET, and abundance of harmful microorganisms in the colon (Spirochaetes, Fusobacteria, Prevotella, Christensenellaceae R7) were lower in the HT and HTK groups than in the LT and LTK groups (P < 0.05). High Trp reduced the expression of virulence genes (K88 and LT) after E. coli F4 attack (P < 0.05). The IL-6, TNF-α was lower in the HTK group than in the LT, LTK group (P < 0.05). In short, a diet containing 0.35% Trp protected piglets from enterotoxigenic E. coli F4 (K88) via Trp metabolism promoting BD expression in the intestinal mucosa, which improved growth and intestinal health.

Asymmetric segregation of maternal mRNAs and germline-related determinants in Cephalochordate embryos: implications for the evolution of early patterning events in chordates.

How animal embryos determine their early cell fates is an important question in developmental biology. In various model animals asymmetrically localized maternal transcripts play important roles in axial patterning and cell fate specification. Cephalochordates (amphioxus), which have three living genera (Asymmetron, Epigonichthys, Branchiostoma), are an early branching chordate lineage and thus occupy a key phylogenetic position for understanding the evolution of chordate developmental mechanisms. It has been shown that in the zygote of Brachiostoma amphioxus, which possess bilateral gonads flanking both sides of their trunk region, maternal transcripts of germline determinants form a compact granule. During early embryogenesis this granule is inherited by a single blastomere that subsequently gives rise to a cluster of cells displaying typical characteristics of primordial germ cells (PGC). These PGCs then come to lie in the tailbud region and proliferate during posterior elongation of the larva to join in the gonad anlagen at the ventral tip of the developing myomeres in amphioxus larvae. However, in Asymmetron and Epigonichthys amphioxus, whose gonads are present only on the right side of their body, nothing is known about their PGC development or the cellular/morphogenetic processes resulting in the asymmetric distribution of gonads. Using conserved germline determinants as markers, we show that similarly to Brachiostoma amphioxus, Asymmetron also employ a preformation mechanism to specify their PGCs, suggesting that this mechanism represents an ancient trait dating back to the common ancestor of Cephalochordates. Surprisingly, we found that Asymmetron PGCs are initially deposited on both sides of the body during early larval development; however, the left side PGCs cease to exist in young juveniles, suggesting that PGCs are eliminated from the left body side during larval development or following metamorphosis. This is reminiscent of the PGC development in the sea urchin embryo, and we discuss the implications of this observation for the evolution of developmental mechanisms.

GPRC5A promotes paclitaxel resistance and glucose content in NSCLC.

Lung cancer is one of the most common and malignant cancers worldwide. Chemotherapy has been widely used in the clinical setting, and paclitaxel is the first-line therapy for lung cancer patients but paclitaxel resistance is the main problem. First, we successfully established paclitaxel-resistant lung cancer cells treated with elevated doses of paclitaxel for 3 months, as confirmed by the CCK-8 assay. Paclitaxel-resistant cancer cells increased glucose content. Second, Gtex, Oncomine, and gene expression omnibus database data mining identified GPRC5A, G protein-coupled receptor, as the most prominent differentially expressed gene in drug-resistant datasets including gemcitabine, paclitaxel, and gefitinib overlapped with the microarray data from cancer cell metabolism. Third, qPCR analysis and western blot technique showed that GPRC5A mRNA and protein levels were significantly enhanced in paclitaxel-resistant lung cancer cells. Fourth, functional analysis was conducted by siRNA-mediated transient knockdown of GPRC5A. Silencing GPRC5A significantly decreased paclitaxel resistance and glucose content. In the end, retinoic acid substantially upregulated GPRC5A proteins and promoted glucose content in two lung cancer cells. Kaplan-Meier plot also confirmed that lung cancer patients with high expression of GPRC5A had a relatively lower survival rate. Our study provided a potential drug target GPRC5A, which may benefit lung cancer patients with acquired paclitaxel resistance in the future and a theoretical basis for future preclinical trials.

Circulating microRNA-33b levels are associated with the presence and severity of coronary heart disease.

MicroRNA-33b (miR-33b) affected various biological pathways in regulating cholesterol homeostasis which may link to the pathogenesis of atherosclerotic lesions. However, whether this marker is associated with the presence and severity of coronary heart disease (CHD) is undetermined. We aim to explore the diagnostic value of circulating miR-33b level in the presence and severity of CHD. Altogether 320 patients were enrolled, including 240 patients diagnosed with CHD while 80 were classified as controls after CAG examination. Circulating miR-33b level was analyzed in all subjects, the Gensini score was calculated to assess the severity of stenotic lesions. The association between miR-33b and the presence and severity of CHD was analyzed, and the diagnostic potential of miR-33b of CHD was performed by the receiver operating characteristic (ROC) analysis. The CHD group had higher miR-33b levels (p < 0.001), and the miR-33b content significantly elevated following an increasing Gensini score (p for trend < 0.001). After adjustments for potential risk factors, such as several blood lipid markers, miR-33b remained a significant determinant for CHD (p < 0.001). ROC analysis disclosed that the AUC was 0.931. The optimal cutoff value of miR-33b was with a sensitivity of 81.3% and a specificity of 98.7% in differentiating CHD. It can prognosticate that the higher level of miR-33b was linked to increased severity of disease in CHD patients. Thus, the application of this marker might assist in the diagnosis and classification of CHD patients. Nevertheless, additional studies with larger sample sizes will be required to verify these results.

TDP-43 deficiency in suprachiasmatic nucleus perturbs rhythmicity of neuroactivity in prefrontal cortex.

Individuals within the amyotrophic lateral sclerosis and frontotemporal dementia disease spectrum (ALS/FTD) often experience disruptive mental behaviors and sleep-wake disturbances. The hallmark of ALS/FTD is the pathological involvement of TAR DNA-binding protein 43 (TDP-43). Understanding the role of TDP-43 in the circadian clock holds promise for addressing these behavioral abnormalities. In this study, we unveil TDP-43 as a pivotal regulator of the circadian clock. TDP-43 knockdown induces intracellular arrhythmicity, disrupts transcriptional activation regulation, and diminishes clock genes expression. Moreover, our experiments in adult mouse reveal that TDP-43 knockdown, specifically within the suprachiasmatic nucleus (SCN), induces locomotor arrhythmia, arrhythmic c-Fos expression, and depression-like behavior. This observation offers valuable insights into the substantial impact of TDP-43 on the behavioral aberrations associated with ALS/FTD. In summary, our study illuminates the significance of TDP-43 in circadian regulation, shedding light on the circadian regulatory mechanisms that may elucidate the pathological underpinnings of ALS/FTD.

Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

N6-methyladenosine-modified circSLCO1B3 promotes intrahepatic cholangiocarcinoma progression via regulating HOXC8 and PD-L1.

BACKGROUND: Refractoriness to surgical resection and chemotherapy makes intrahepatic cholangiocarcinoma (ICC) a fatal cancer of the digestive system with high mortality and poor prognosis. Important function invests circRNAs with tremendous potential in biomarkers and therapeutic targets. Nevertheless, it is still unknown how circRNAs contribute to the evolution of ICC. METHODS: CircRNAs in paired ICC and adjacent tissues were screened by circRNAs sequencing. To explore the impact of circRNAs on ICC development, experiments involving gain and loss of function were conducted. Various experimental techniques, including quantitative real-time PCR (qPCR), western blotting, RNA immunoprecipitation (RIP), luciferase reporter assays, RNA pull-down, chromatin immunoprecipitation (ChIP), ubiquitination assays and so on were employed to identify the molecular regulatory role of circRNAs. RESULTS: Herein, we reported a new circRNA, which originates from exon 9 to exon 15 of the SLCO1B3 gene (named circSLCO1B3), orchestrated ICC progression by promoting tumor proliferation, metastasis and immune evasion. We found that the circSLCO1B3 gene was highly overexpressed in ICC tissues and related to lymphatic metastasis, tumor sizes, and tumor differentiation. Mechanically, circSLCO1B3 not only promoted ICC proliferation and metastasis via miR-502-5p/HOXC8/SMAD3 axis, but also eradicated anti-tumor immunity via suppressing ubiquitin-proteasome-dependent degradation of PD-L1 by E3 ubiquitin ligase SPOP. We further found that methyltransferase like 3 (METTL3) mediated the m6A methylation of circSLCO1B3 and stabilizes its expression. Our findings indicate that circSLCO1B3 is a potential prognostic marker and therapeutic target in ICC patients. CONCLUSIONS: Taken together, m6A-modified circSLCO1B3 was correlated with poor prognosis in ICC and promoted ICC progression not only by enhancing proliferation and metastasis via potentiating HOXC8 expression, but also by inducing immune evasion via antagonizing PD-L1 degradation. These results suggest that circSLCO1B3 is a potential prognostic marker and therapeutic target for ICC.

A pH/ROS-responsive antioxidative and antimicrobial GelMA hydrogel for on-demand drug delivery and enhanced osteogenic differentiation in vitro.

Long-term inflammation, including those induced by bacterial infections, contributes to the superfluous accumulation of reactive oxygen species (ROS), further aggravating this condition, decreasing the local pH, and adversely affecting bone defect healing. Conventional drug delivery scaffold materials struggle to meet the demands of this complex and dynamic microenvironment. In this work, a smart gelatin methacryloyl (GelMA) hydrogel was synthesized for the dual delivery of proanthocyanidin and amikacin based on the unique pH and ROS responsiveness of boronate complexes. Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) demonstrated the co-crosslinking of two boronate complexes with GelMA. The addition of the boronate complexes improved the mechanical properties, swelling ratio, degradation kinetics and antioxidative properties of the hydrogel. The hydrogel exhibited pH and ROS responses and a synergistic control over the drug release. Proanthocyanidin was responsively released to protect mouse osteoblast precursor cells from oxidative stress and promote their osteogenic differentiation. The hydrogel responded to pH changes and released sufficient amikacin in a timely manner, thereby exerting an efficient antimicrobial effect. Overall, the hydrogel delivery system exhibited a promising strategy for solving infectious and inflammatory problems in bone defects and promoting early-stage bone healing.

A case of cardiac tamponade occurred 1 day after transcatheter atrial septal defect closure.

Transesophageal echocardiography (TEE) shows pericardial effusion and a gap between the left atrium and the aortic sinus by atrial septal defect occluder.

Allergenicity Modulation of Casein with the Modifications of Linearization, Cross-Linking, and Glycation via the Regulation of Th1/Th2 Homeostasis.

Casein (CN) is the primary allergenic protein in cow's milk, contributing to the worldwide escalating prevalence of food allergies. However, there remains limited knowledge regarding the effect of structural modifications on CN allergenicity. Herein, we prepared three modified CNs (mCN), including sodium dodecyl sulfate and dithiothreitol-induced linear CN (LCN), transglutaminase-cross-linked CN (TCN), and glucose-glycated CN (GCN). The electrophoresis results indicated widespread protein aggregation among mCN, causing variations in their molecular weights. The unique internal and external structural characteristics of mCN were substantiated by disparities in surface microstructure, alterations in the secondary structure, variations in free amino acid contents, and modifications in functional molecular groups. Despite the lower digestibility of TCN and GCN compared to LCN, they significantly suppressed IL-8 production in Caco-2 cells without significantly promoting their proliferation. Moreover, GCN showed the weakest capacity to induce LAD2 cell degranulation. Despite the therapeutic effect of TCN, GCN-treated mice displayed the most prominent attenuation of allergic reactions and a remarkably restored Th1/Th2 imbalance, while LCN administration resulted in severe allergic phenotypes and endotypes in both cellular and murine models. This study highlighted the detrimental effect of linear modifications and underscored the significance of glycation in relation to CN allergenicity.

CCR5 and inflammatory storm.

Chemokines and their corresponding receptors play crucial roles in orchestrating inflammatory and immune responses, particularly in the context of pathological conditions disrupting the internal environment. Among these receptors, CCR5 has garnered considerable attention due to its significant involvement in the inflammatory cascade, serving as a pivotal mediator of neuroinflammation and other inflammatory pathways associated with various diseases. However, a notable gap persists in comprehending the intricate mechanisms governing the interplay between CCR5 and its ligands across diverse and intricate inflammatory pathologies. Further exploration is warranted, especially concerning the inflammatory cascade instigated by immune cell infiltration and the precise binding sites within signaling pathways. This study aims to illuminate the regulatory axes modulating signaling pathways in inflammatory cells by providing a comprehensive overview of the pathogenic processes associated with CCR5 and its ligands across various disorders. The primary focus lies on investigating the pathomechanisms associated with CCR5 in disorders related to neuroinflammation, alongside the potential impact of aging on these processes and therapeutic interventions. The discourse culminates in addressing current challenges and envisaging potential future applications, advocating for innovative research endeavors to advance our comprehension of this realm.

[Association of polymorphisms in SEC16B, DNAJC27, FTO and MC4R genes with overweight and obesity in Han preschool children].

OBJECTIVE: To investigate the association of polymorphisms in SEC16B rs633715, DNAJC27 rs713586, FTO rs11642015 and MC4R rs6567160 with overweight and obesity in Han Chinese preschool children. METHODS: A total of 749 Han Chinese preschool children from Henan and Guizhou Province of Long-term Health Effects Assessment Project of Infants and Toddlers Nutritional Pack were selected for the study and divided into an overweight and obese group and a normal control group in 2022. rs633715, rs713586, rs11642015 and rs6567160 were genotyped using Kompetitive allele-specific PCR(KASP) technology. The distribution of genotypic polymorphisms was compared using the χ~2 test. The association between the four loci and overweight and obesity in preschool children was analyzed using a multifactorial logistic regression model. RESULTS: The statistical analysis revealed a significant disparity(P<0.05) in the distribution of genotypic polymorphisms of rs633715 and rs6567160 among preschoolers in Henan and Guizhou Province. CC heterozygous mutant and recessive models at rs633715 locus were associated with susceptibility to overweight and obesity in preschool children [OR and 95% CI 2.915(1.163-7.305), and 2.997(1.226-7.323), respectively, both P<0.05]. TC heterozygous mutant and dominant models at rs713586 locus were also associated susceptibility to overweight and obesity in preschool children(OR and 95% CI were 2.362(1.054-5.289)and 2.362(1.054-5.289), respectively, both P<0.05). rs11642015 and rs6567160 loci were not associated with susceptibility to overweight and obesity in preschool children(P>0.05). The result of the analysis of the cumulative effect of rs633715 and rs713586 showed that the number of genotypes carrying the risk genotype was positively associated with the risk of overweight and obesity in preschool children(P_(trend)<0.01). CONCLUSION: Among Han Chinese preschool children, SEC16B rs633715 and DNAJC27 rs713586 were associated with susceptibility to overweight and obesity in preschool children. Moreover, rs633715 and rs713586 had a cumulative effect on susceptibility to overweight and obesity in preschool children, the number of risk genotypes carried was positively associated with childhood overweight and obesity risk.

A metal-organic framework and quantum dot-based ratiometric fluorescent probe for the detection of formaldehyde in food.

A green and sensitive ratio fluorescence strategy was proposed for the detection of formaldehyde (FA) in food based on a kind of metal-organic frameworks (MOFs), MIL-53(Fe)-NO2, and nitrogen-doped Ti3C2 MXene quantum dots (N-Ti3C2 MQDs) with a blue fluorescence at 450 nm. As a type of MOFs with oxidase-like activity, MIL-53(Fe)-NO2 can catalyze o-phenylenediamine (OPD) into yellow fluorescent product 2,3-diaminophenazine (DAP) with a fluorescent emission at 560 nm. DAP has the ability to suppress the blue light of N-Ti3C2 MQDs due to inner filter effect (IFE). Nevertheless, Schiff base reaction can occur between FA and OPD, inhibiting DAP production. This results in a weakening of the IFE which reverses the original fluorescence color and intensity of DAP and N-Ti3C2 MQDs. So, the ratio of fluorescence intensity detected at respective 450 nm and 560 nm was designed as the readout signal to detect FA in food. The linear range of FA detection was 1-200 µM, with a limit of detection of 0.49 µM. The method developed was successfully used to detect FA in food with satisfactory results. It indicates that MIL-53(Fe)-NO2, OPD, and N-Ti3C2 MQDs (MON) system constructed by integrating the mimics enzyme, enzyme substrate, and fluorescent quantum dots has potential application for FA detection in practical samples.

Sandwich-like CuNPs@AgNPs@PSB SERS substrates for sensitive detection of R6G and Forchlorfenuron.

The development of a highly sensitive, synthetically simple and economical SERS substrate is technically very important. A fast, economical, sensitive and reproducible CuNPs@AgNPs@ Porous silicon Bragg reflector (PSB) SERS substrate was prepared by electrochemical etching and in situ reduction method. The developed CuNPs@AgNPs@PSB has a large specific surface area and abundant "hot spot" region, which makes the SERS performance excellent. Meanwhile, the successful synthesis of CuNPs@AgNPs can not only modulate the plasmon resonance properties of nanoparticles, but also effectively prolong the time stability of Cu nanoparticles. The basic performance of the substrate was evaluated using rhodamine 6G (R6G). (Detection limit reached 10-15 M, R2 = 0.9882, RSD = 5.3 %) The detection limit of Forchlorfenuron was 10 µg/L. The standard curve with a regression coefficient of 0.979 was established in the low concentration range of 10 µg/L -100 µg/L. This indicates that the prepared substrates can accomplish the detection of pesticide residues in the low concentration range. The prepared high-performance and high-sensitivity SERS substrate have a very promising application in detection technology.

Management of incessant ventricular arrhythmias in a patient with left ventricular assist device: a case report.

BACKGROUND: The implantation of left ventricular assist devices (LVADs) as a bridge to transplantation or as destination therapy in end-stage heart failure patients is frequently complicated by the emergence of ventricular arrhythmias (VAs). These arrhythmias have been implicated in precipitating deleterious clinical outcomes, increased mortality rates and augmented healthcare expenditures. CASE PRESENTATION: We present a challenging case of a 49-year-old male with a history of dilated cardiomyopathy who received an LVAD. Post-implantation, the patient suffered from intractable VAs, leading to multiple rehospitalizations and hemodynamic deterioration. Despite exhaustive medical management and electrical cardioversion attempts, the patient's VAs persisted, ultimately necessitating prioritization for cardiac transplantation. DISCUSSION: This case highlights the challenges in managing VAs in LVAD patients and the importance of multidisciplinary collaboration. While pharmacological intervention is the initial strategy, catheter ablation may be considered in selected cases when medication is insufficient. In instances of intractable VAs, expeditious listing for heart transplantation as a high-priority candidate is advisable when feasible.

Transformation of motion pattern selectivity from retina to superior colliculus.

The superior colliculus (SC) is a prominent and conserved visual center in all vertebrates. In mice, the most superficial lamina of the SC is enriched with neurons that are selective for the moving direction of visual stimuli. Here we study how these direction selective neurons respond to complex motion patterns known as plaids, using two-photon calcium imaging in awake male and female mice. The plaid pattern consists of two superimposed sinusoidal gratings moving in different directions, giving an apparent pattern direction that lies between the directions of the two component gratings. Most direction selective neurons in the mouse SC respond robustly to the plaids and show a high selectivity for the moving direction of the plaid pattern but not of its components. Pattern motion selectivity is seen in both excitatory and inhibitory SC neurons and is especially prevalent in response to plaids with large cross angles between the two component gratings. However, retinal inputs to the SC are ambiguous in their selectivity to pattern versus component motion. Modeling suggests that pattern motion selectivity in the SC can arise from a nonlinear transformation of converging retinal inputs. In contrast, the prevalence of pattern motion selective neurons is not seen in the primary visual cortex (V1). These results demonstrate an interesting difference between the SC and V1 in motion processing and reveal the SC as an important site for encoding pattern motion.Significance Statement An important function of the visual system is to encode the direction of complex motion patterns in the environment. Studies using the plaid stimulus have revealed neurons in different cortical areas that are tuned to either pattern motion or component motion, but how neurons in the SC respond to plaids has not been studied. Here we show that direction selective neurons in the mouse SC respond to plaids with a clear pattern motion selectivity, at a level not seen in the retina or V1. Our results thus provide new information regarding the function and organization of the early visual system and highlight the importance of SC circuits in computing complex motion.

Efficacy and safety of minimally invasive laparoscopic surgery under general anesthesia for ovarian cancer.

BACKGROUND: Ovarian cancer is one of the most common malignant tumors in female reproductive system in the world, and the choice of its treatment is very important for the survival rate and prognosis of patients. Traditional open surgery is the main treatment for ovarian cancer, but it has the disadvantages of big trauma and slow recovery. With the continuous development of minimally invasive technology, minimally invasive laparoscopic surgery under general anesthesia has been gradually applied to the treatment of ovarian cancer because of its advantages of less trauma and quick recovery. However, the efficacy and safety of minimally invasive laparoscopic surgery under general anesthesia in the treatment of ovarian cancer are still controversial. AIM: To explore the efficacy and safety of general anesthesia minimally invasive surgery in the treatment of ovarian cancer. METHODS: The clinical data of 90 patients with early ovarian cancer in our hospital were analyzed retrospectively. According to the different surgical treatment methods, patients were divided into study group and control group (45 cases in each group). The study group received minimally invasive laparoscopic surgery under general anesthesia for ovarian cancer, while the control group received traditional open surgery for ovarian cancer. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), clinical efficacy and safety of the two groups were compared. RESULTS: The intraoperative blood loss, length of hospital stay, postoperative gas evacuation time, and postoperative EORTC QLQ-C30 score of the study group were significantly better than those of the control group (P < 0.05). The incidence of postoperative complications in the study group was significantly lower than in the control group (P < 0.05). The two groups had no significant differences in the preoperative adrenocorticotropic hormone (ACTH), androstenedione (AD), cortisol (Cor), cluster of differentiation 3 positive (CD3+), and cluster of differentiation 4 positive (CD4+) indexes (P > 0.05). In contrast, postoperatively, the study group's ACTH, AD, and Cor indexes were lower, and the CD3+ and CD4+ indexes were higher than those in the control group (P < 0.05). CONCLUSION: Minimally invasive laparoscopic surgery under general anesthesia in patients with early ovarian cancer can significantly improve the efficacy and safety, improve the short-term prognosis and quality of life of patients, and is worth popularizing.

ARID1B Deficiency Leads to Impaired DNA Damage Response and Activated cGAS-STING Pathway in Non-Small Cell Lung Cancer.

Purpose: Lung cancer is a major cause of morbidity and mortality globally, necessitating the identification of predictive markers for effective immunotherapy. Mutations in SWI/SNF chromatin remodeling complex genes were reported sensitized human tumors to immune checkpoint inhibitors (ICIs), but the underlying mechanisms are unclear. This study aims to investigate the association between SWI/SNF gene ARID1B mutation and ICI response in non-small cell lung cancer (NSCLC) patients, to explore the functional consequences of ARID1B mutation on DNA damage response, immune microenvironment, and cGAS-STING pathway activation. Methods: TCGA LUAD, LUSC, and AACR GENIE data are analyzed to assess ARID1B mutation status in NSCLC patients. Prognostic analysis evaluates the effect of ARID1B mutation on patient outcomes. In vitro experiments carried to investigate the consequences of ARID1B knockdown on DNA damage response and repair. The immune microenvironment is assessed based on ARID1B expression, and the relationship between ARID1B and the cGAS-STING pathway is explored. Results: ARID1B mutation frequency is 5.7% in TCGA databases and 4.4% in the AACR GENIE project. NSCLC patients with ARID1B mutation showed improved overall and progression-free survival following ICIs treatment. ARID1B knockdown in lung cancer cell lines enhances DNA damage, impairs DNA repair, alters chromatin accessibility, and activates the cGAS-STING pathway. ARID1B deficiency is associated with immune suppression, indicated by reduced immune scores, decreased immune cell infiltration, and negative correlations with immune-related cell types and functions. Conclusion: ARID1B mutation may predict improved response to ICIs in NSCLC patients. ARID1B mutation leads to impaired DNA damage response and repair, altered chromatin accessibility, and cGAS-STING pathway activation. These findings provide insights into ARID1B's biology and therapeutic implications in lung cancer, highlighting its potential as a target for precision medicine and immunotherapy. Further validation and clinical studies are warranted.

Wastewater-based Epidemiology for COVID-19 Surveillance: A Survey.

The pandemic of COVID-19 has imposed tremendous pressure on public health systems and social economic ecosystems over the past years. To alleviate its social impact, it is important to proactively track the prevalence of COVID-19 within communities. The traditional way to estimate the disease prevalence is to estimate from reported clinical test data or surveys. However, the coverage of clinical tests is often limited and the tests can be labor-intensive, requires reliable and timely results, and consistent diagnostic and reporting criteria. Recent studies revealed that patients who are diagnosed with COVID-19 often undergo fecal shedding of SARS-CoV-2 virus into wastewater, which makes wastewater-based epidemiology (WBE) for COVID-19 surveillance a promising approach to complement traditional clinical testing. In this paper, we survey the existing literature regarding WBE for COVID-19 surveillance and summarize the current advances in the area. Specifically, we have covered the key aspects of wastewater sampling, sample testing, and presented a comprehensive and organized summary of wastewater data analytical methods. Finally, we provide the open challenges on current wastewater-based COVID-19 surveillance studies, aiming to encourage new ideas to advance the development of effective wastewater-based surveillance systems for general infectious diseases.