Multi-region calcium imaging in freely behaving mice with ultra-compact head-mounted fluorescence microscopes.

To investigate the circuit-level neural mechanisms of behavior, simultaneous imaging of neuronal activity in multiple cortical and subcortical regions is highly desired. Miniature head-mounted microscopes offer the capability of calcium imaging in freely behaving animals. However, implanting multiple microscopes on a mouse brain remains challenging due to space constraints and the cumbersome weight of the equipment. Here, we present TINIscope, a Tightly Integrated Neuronal Imaging microscope optimized for electronic and opto-mechanical design. With its compact and lightweight design of 0.43 g, TINIscope enables unprecedented simultaneous imaging of behavior-relevant activity in up to four brain regions in mice. Proof-of-concept experiments with TINIscope recorded over 1000 neurons in four hippocampal subregions and revealed concurrent activity patterns spanning across these regions. Moreover, we explored potential multi-modal experimental designs by integrating additional modules for optogenetics, electrical stimulation or local field potential recordings. Overall, TINIscope represents a timely and indispensable tool for studying the brain-wide interregional coordination that underlies unrestrained behaviors.

A shock flash breaking out of a dusty red supergiant.

Shock-breakout emission is light that arises when a shockwave, generated by the core-collapse explosion of a massive star, passes through its outer envelope. Hitherto, the earliest detection of such a signal was at several hours after the explosion1, although a few others had been reported2-7. The temporal evolution of early light curves should provide insights into the shock propagation, including explosion asymmetry and environment in the vicinity, but this has been hampered by the lack of multiwavelength observations. Here we report the instant multiband observations of a type II supernova (SN 2023ixf) in the galaxy M101 (at a distance of 6.85 ± 0.15 Mpc; ref. 8), beginning at about 1.4 h after the explosion. The exploding star was a red supergiant with a radius of about 440 solar radii. The light curves evolved rapidly, on timescales of 1-2 h, and appeared unusually fainter and redder than predicted by the models9-11 within the first few hours, which we attribute to an optically thick dust shell before it was disrupted by the shockwave. We infer that the breakout and perhaps the distribution of the surrounding dust were not spherically symmetric.

Feasibility of novel intraoperative navigation for anatomical liver resection using real-time virtual sonography combined with indocyanine green fluorescent imaging technology.

To analyze the feasibility and clinical effect of novel intraoperative navigation of real-time virtual sonography (RVS) combined with indocyanine green (ICG) fluorescent imaging technology in anatomical liver resection (ALR) for hepatocellular carcinoma. The clinical data of 41 patients who underwent ALR using RVS intraoperative navigation combined with ICG fluorescent imaging technology in the Department of Hepatobiliary Surgery of Peking University International Hospital from January 2020 to May 2022 were retrospectively analyzed. RVS was applied to guide the surgical plane through fusing real-time intraoperative ultrasound images with corresponding preoperative CT or MRI images. Operation methods, operation time, intraoperative blood loss, operative margin, hospital stay and postoperative complications were analyzed. The 1-year overall survival rate and tumor-free survival rate of patients were followed up by outpatient review or telephone calls. ALR surgery was performed on each of 41 patients. There were no deaths during perioperative period and postoperative complications occurred in 7 cases (17.1%). The postoperative pathological examinations demonstrated all cases of hepatocellular carcinoma and negative operative margins. The 41 patients were followed up for 12 to 20 months, with a median follow-up time of 14 months. The overall survival rate 1 year after surgery was 100.0% (41/41), 3 patients (7.3%) experienced tumor recurrence, and the tumor-free survival rate of 1 year after surgery was 92.7% (38/41). In conclusion, novel intraoperative navigation of RVS combined with ICG fluorescent imaging technology is safe and feasible in anatomical segmental hepatectomy of hepatocellular carcinoma.

Associations of fruit, whole grain, and total energy intakes with gut microbiome diversity and composition.

Background: The relationship between fruit, whole grain, and total energy consumption and the gut microbiome in the Chinese population remains unclear. Objective: We investigated the relationship between intakes of fruits, whole grains, and energy, and the diversity and composition of gut microbiota. Design: This cross-sectional study included 167 subjects aged 40-75 years who underwent colonoscopy at Nankai Hospital in Tianjin, China. Each of the participants completed a personal history questionnaire, a 7-day dietary record, and donated a fecal sample. The V3-V4 hypervariable region of the bacterial 16S rRNAgene was amplified and sequenced using Illumina Novaseq. The relationship between diet and gut microbiota was evaluated in terms of both the overall composition and the abundance of specific taxon. Results: Fruits intake was positively related to the abundance of Bacilli, Porphyromonadaceae, Streptococcaceae, Parabacteroides, Streptococcus, and Bilophila in fecal samples. Higher whole grains intake was associated with higher microbial diversity, as measured by Shannon, Simpson, and Chao1 indices. Specifically, there was a significant increase inthe relative abundance of Lachnospiraceae and a decrease in Actinobacteria with increased whole grains intake. Moreover, higher intake of total energy was associated with a lower abundance of Anaerostipes and a higher abundance of Lactobacillales and Acidaminococcus. Conclusion: Whole grains intake was positively associated with gut microbial diversity. Fruits and total energy intake were related to the abundance of specifictaxon (e.g., Bacilli and Acidaminococcus). These findings highlight the potential importance of dietary interventions for modulating gut microbiota composition and promoting overall health.

The Association between Vitamin D Deficiency and Changes in Cognitive Functions in Chinese Older Adults: A Prospective Cohort Study.

BACKGROUND: Along with the problem of population aging, the prevalence of dementia is gradually increasing. Associations between vitamin D deficiency (VDD) and cognitive functions remain unclear. OBJECTIVES: We aimed to determine the relationship between VDD and changes in cognitive performance in community-dwelling older adults. METHODS: In this longitudinal cohort study, participants aged ≥65 years were enrolled in March, 2016. The serum level of 25-hydroxy-vitamin D was analyzed by liquid-chromatography-tandem-- mass-spectrometry at baseline. VDD was defined as less than 20 ng/mL. All participants completed a health status questionnaire. Cognitive functions were evaluated by the Wechsler Adult Intelligence Scale-Revised in China at baseline and each visit. The linear mixed-effects model was utilized to examine the association between baseline VDD and changes in cognitive functions. RESULTS: In total, 866 participants were included in our study, with a mean duration of 3 years. VDD was markedly associated with lower full intelligence quotient (FIQ) (ß: -3.355, 95% confidence interval [CI]:-4.165,-2.545), verbal intelligence quotient (VIQ) (ß: -3.420, 95%CI: -4.193,-2.647), performance intelligence quotient (PIQ) (ß: -2.610, 95%CI: -3.683,-1.537), comprehension (ß: -0.630, 95%CI: -1.022,-0.238), information (ß: -0.354, 95%CI: -0.699,-0.008), arithmetic (ß: -1.065, 95%CI: -1.228,-0.902), digit span (ß: -0.370, 95%CI: -0.547,-0.192), vocabulary (ß: -0.789, 95%CI: -1.084,-0.493), picture completion (ß: -0.391, 95%CI: -0.761,-0.022), block design (ß: -0.412, 95%CI: -0.697,-0.127), picture arrangement (ß: -0.542, 95%CI: -0.909,-0.174), and object assembly (ß: -0.492, 95%CI: -0.818,-0.165) than those with adequacy. CONCLUSION: A higher frequency of VDD was associated with lower scores of FIQ, VIQ, PIQ and subtests on memory and executive function. Future randomized controlled trials are warranted to further verify the conclusions.

Comparison of Efficacy and Safety of Anti-Programmed Cell Death-1 Antibody Plus Lenvatinib and Chemotherapy as First-Line Therapy for Patients with Stage IV Gallbladder Cancer: A Real-World Study in a Chinese Population.

Background: The present study aimed to evaluate and compare the efficacy and safety of anti-programmed cell death protein 1 (anti-PD-1) antibody plus lenvatinib (tyrosine kinase inhibitor) therapy and chemotherapy as the first-line treatment to unresectable stage IV gallbladder cancer (GBC). Methods: We retrospectively analyzed the clinical data of patients with stage IV GBC who received chemotherapy or anti-PD-1 antibody combined with lenvatinib therapy at our hospital from March 2018 to October 2022. Patients with previous antitumor treatment were excluded. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were assessed. Results: A total of 64 patients were enrolled, of which 33 patients received chemotherapy (gemcitabine + cisplatin) in the chemotherapy group, and 31 patients received anti-PD-1antibody (camrelizumab) combined with lenvatinib therapy in the combined therapy group. The median OS was 12.00 months in the combined therapy group and 10.00 months in the chemotherapy group (hazard ratio (HR), 0.57; 95% CI: 0.32-1.03; p < 0.05). The median PFS was 9.00 months in the combined therapy group and 6.00 months in the chemotherapy group (HR, 0.46; 95% CI: 0.25-0.84; p < 0.01). The ORR was 54.84% and 39.39% in the combined therapy and chemotherapy groups, respectively, and the difference was not significant (p = 0.22). The DCR was 80.65% and 72.72% in the combined therapy and chemotherapy groups, respectively (p = 0.46). One patient successfully underwent radical surgery after 8 months of combined therapy and achieved a pathological complete response. Furthermore, no patients experienced AEs of hematologic toxic effects in the combined therapy group compared with the chemotherapy group, demonstrating the advantage of the combined therapy. Conclusions: Anti-PD-1 antibody combined with lenvatinib may be a potentially effective and tolerable first-line treatment for unresectable stage IV GBC.

The Correlation between Islet ß Cell Secretion Function and Gallbladder Stone Disease: A Retrospective Study Based on Chinese Patients with Newly Diagnosed Type 2 Diabetes Mellitus.

BACKGROUND: This study aimed to analyze the correlation between islet ß cell function and gallbladder stone (GBS) in newly diagnosed type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 438 newly diagnosed T2DM patients in Peking University International Hospital from January 2017 to August 2022 were retrospectively analyzed and divided into a non-GBS group and a GBS group. RESULTS: (1) The homeostasis model assessment of the insulin resistance (HOMA-IR) of the GBS group was higher than that of the non-GBS group (p < 0.05), while the homeostasis model assessment of ß cell (HOMA-ß), disposition index (DI0), and Matsuda index of the GBS group were lower than those of the non-GBS group (all p < 0.05). (2) For male patients, HOMA-IR is an independent risk factor for GBS (OR = 2.00, 95% CI:1.03, 3.88, p < 0.05), and the Matsuda index value is a protective factor for GBS (OR = 0.76, 95% CI:0.60, 0.96, p < 0.05). For female patients, HOMA-IR is an independent risk factor for GBS (OR = 2.80, 95% CI:1.03, 7.58, p < 0.05) and the Matsuda index value is a protective factor for GBS (OR = 0.59, 95% CI:0.39, 0.90, p < 0.05). (3) For male patients, the area under curve (AUC) for predicting GBS was 0.77 (95% CI 0.67, 0.87), with a specificity of 75.26%, a sensitivity of 80.00%, and an accuracy of 75.64%. For female patients, the AUC for predicting GBS was 0.77 (95% CI 0.63, 0.88), with a specificity of 79.63%, a sensitivity of 71.43%, and an accuracy of 78.69%. CONCLUSIONS: Insulin resistance may be an independent risk factor for the incidence of GBS in patients with newly diagnosed T2DM, both male or female, which provides a new clinical basis and research direction for the prevention and treatment of GBS in patients with T2DM. This study has established a predictive model of GBS in T2DM and found it to be accurate, thus representing an effective tool for the early prediction of GBS in patients with T2DM.

Design of Novel Knot-like Structures Based on Ovotransferrin Fibril-Gum Arabic Complexes: Effective Strategies to Stabilize Pickering Emulsions.

This work aimed to clarify the effects of gum arabic (GA) on the morphology and properties of ovotransferrin fibrils (OVTFs). By constructing OVTF-GA complexes and exploring the dispersion stability, turbidity and the ζ-potential of the complexes, the optimum mass ratio of OVTFs to GA and pH for complex formation were confirmed as being 1:1 and pH 4.6, respectively. The interaction between OVTFs and GA was determined to be predominantly driven by electrostatic attraction. The OVTF-GA complexes exhibited a knot-like structure when observed using atomic force microscopy. Then, OVTFs and OVTF-GA complexes were compared in terms of contact angle, surface hydrophobicity and dynamic interfacial tension. The combination of OVTFs and GA decreased the contact angle of OVTFs from 80.85° to 70.36°. In comparison with OVTFs, OVTF-GA complexes reduced the oil-water interfacial tension to a lower level (8.14 mN/m). Furthermore, the capacities of OVTF-GA complexes in stabilizing emulsions were explored. OVTF-GA complex-stabilized oleogel-based Pickering emulsion (OGPE) was constructed, and OVTF-stabilized oleogel-based Pickering emulsion (OPE) was used as the control. OGPE had a higher emulsified phase volume fraction (EPVF) and stability index (SI). The EPVF of OGPE was 100.0% and 99.4% before and after one-month storage, respectively, compared with 98.3% and 95.7% of OPE. This work can provide some useful references for the design of biopolymers with novel structures composed of protein fibrils and polysaccharides, which may also help to construct and apply protein fibril-polysaccharide complexes under specific needs.

Healthy aging, early screening, and interventions for frailty in the elderly.

With the intensification of population aging worldwide, the health problems of the elderly have become a particular concern. Functional disability is a prominent problem in the aging of this population, resulting in the decreased quality of life of senile people. Risk factors for functional disability in the elderly include geriatric syndromes and the associated diseases such as frailty. The influence of frailty on the health of the elderly has been a hot topic in recent years. As a dynamic and reversible geriatric syndrome, it has become one of the important public health problems emerging around the world. Frailty lies between self-reliance and the need for care and is reversible. Reasonable preventive interventions can restore the elderly to an independent life. If no interventions are implemented, the elderly will face a dilemma. There is no gold standard for frailty screening around the world. In order to alleviate frailty in the elderly, many countries have conducted early screening for frailty, mainly focusing on nutrition, physical activity, and social participation, in order to detect and prevent frailty earlier and to reduce the incidence of frailty. This topic provides an overview of the current status of frailty, early screening for frailty, and the interventions for frailty in most countries of the world.

The prognostic ability of radiotherapy of different colorectal cancer histological subtypes and tumor sites.

The prognostic significance of radiotherapy (RT) for colorectal cancer (CRC) has shown conflicting results, particularly among different pathological subtypes, including adenocarcinoma (AC), mucinous adenocarcinoma (MC), and signet-ring cell carcinoma (SR). This study analyzed the prognosis of three pathological CRC types and focused on the prognostic significance of RT on three CRC histological subtypes. Patients diagnosed with AC (n = 54,174), MC (n = 3813), and SR (n = 664) in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database (2010-2017) were evaluated. Cox regression models and competitive risk models were built to assess the effect of RT on the risk of CRC-associated death. Potential interactions between RT and stratified variables including age, sex, and tumor location were examined by multiplicative models. Compared with AC patients, SR patients had the worst overall survival (OS) among 3 subtypes of CRC (log-rank test, p < 0.001). Compared with patients who did not receive radiotherapy, RT was associated with a 1.09-fold (HR = 1.09, 95%[CI]: 1.03, 1.15) elevated risk of death among AC patients. In the SR group, RT significantly reduced the risk of death by 39% (HR = 0.61, 95%[CI]: 0.39-0.95). However, RT did not appear to independently influence survival in the MC group (HR = 0.96, 95%[CI]: 0.77, 1.21). In the subgroup analysis, tumor location (colon and rectum) significantly modified the association between RT and the risk of death among the AC and SR patients (p for interaction < 0.05). SR patients exhibited a worse OS (overall survival) than AC patients, and the effect of RT varied according to CRC histological subtypes. This can ultimately lead to more personalized and effective treatment strategies for CRC patients.

Chemo-Free Treatment Using Anti-PD-1 Antibodies with Lenvatinib in Unresectable Gallbladder Cancer: PD-L1 May Be a Potential Biomarker for a Better Outcome.

BACKGROUND: Recently, anti-PD-1 antibodies plus lenvatinib has been administered in a series of solid tumors. Yet, the efficacy of chemo-free treatment of this combined therapy has seldom been reported in gallbladder cancer (GBC). The aim of our study was to initially evaluate the efficacy of the chemo-free treatment in unresectable GBCs. METHODS: We retrospectively collected the clinical data of unresectable GBCs treated using chemo-free anti-PD-1 antibodies plus lenvatinib in our hospital from March 2019 to August 2022. The clinical responses were assessed, and PD-1 expression was evaluated. RESULTS: Our study enrolled 52 patients, with the median progression-free survival being 7.0 months and the median overall survival being 12.0 months. The objective response rate was 46.2% and the disease control rate was 65.4%. The expression of PD-L1 in patients with objective response was significantly higher than those with progression of disease. CONCLUSIONS: For patients with unresectable GBC, when not eligible for systemic chemotherapy, chemo-free treatment using anti-PD-1 antibodies with lenvatinib may become a safe and rational choice. The expression of PD-L1 in tumor tissues may be correlated to the objective response, and thus is expected to be a predictor of efficacy, and further clinical studies are certainly needed.

An Adaptive Brain-Computer Interface to Enhance Motor Recovery After Stroke.

Brain computer interfaces (BCIs) have been demonstrated to have the potential to enhance motor recovery after stroke. However, some stroke patients with severe paralysis have difficulty achieving the BCI performance required for participating in BCI-based rehabilitative interventions, limiting their clinical benefits. To address this issue, we presented a BCI intervention approach that can adapt to patients' BCI performance and reported that adaptive BCI-based functional electrical stimulation (FES) treatment induced clinically significant, long-term improvements in upper extremity motor function after stroke more effectively than FES treatment without BCI intervention. These improvements were accompanied by a more optimized brain functional reorganization. Further comparative analysis revealed that stroke patients with low BCI performance (LBP) had no significant difference from patients with high BCI performance in rehabilitation efficacy improvement. Our findings suggested that the current intervention may be an effective way for LBP patients to engage in BCI-based rehabilitation treatment and may promote lasting motor recovery, thus contributing to expanding the applicability of BCI-based rehabilitation treatments to pave the way for more effective rehabilitation treatments.

A new paradigm of learned cooperation reveals extensive social coordination and specific cortical activation in mice.

Cooperation is a social behavior crucial for the survival of many species, including humans. Several experimental paradigms have been established to study cooperative behavior and related neural activity in different animal species. Although mice exhibit limited cooperative capacity in some behavioral paradigms, it is still interesting to explore their cooperative behavior and the underlying neural mechanisms. Here, we developed a new paradigm for training and testing cooperative behavior in mice based on coordinated lever-pressing and analyzed social interactions between the animals during cooperation. We observed extensive social contact and waiting behavior in cooperating animals, with the number of such events positively correlated with the success of cooperation. Using c-Fos immunostaining and a high-speed volumetric imaging with synchronized on-the-fly scan and readout (VISoR) system, we further mapped whole-brain neuronal activity trace following cooperation. Significantly higher levels of c-Fos expression were observed in cortical areas including the frontal pole, motor cortex, anterior cingulate area, and prelimbic area. These observations highlight social interaction and coordination in cooperative behavior and provide clues for further study of the underlying neural circuitry mechanisms.

Metabolomic analysis of maternal mid-gestation plasma and cord blood in autism spectrum disorders.

The discovery of prenatal and neonatal molecular biomarkers has the potential to yield insights into autism spectrum disorder (ASD) and facilitate early diagnosis. We characterized metabolomic profiles in ASD using plasma samples collected in the Norwegian Autism Birth Cohort from mothers at weeks 17-21 gestation (maternal mid-gestation, MMG, n = 408) and from children on the day of birth (cord blood, CB, n = 418). We analyzed associations using sex-stratified adjusted logistic regression models with Bayesian analyses. Chemical enrichment analyses (ChemRICH) were performed to determine altered chemical clusters. We also employed machine learning algorithms to assess the utility of metabolomics as ASD biomarkers. We identified ASD associations with a variety of chemical compounds including arachidonic acid, glutamate, and glutamine, and metabolite clusters including hydroxy eicospentaenoic acids, phosphatidylcholines, and ceramides in MMG and CB plasma that are consistent with inflammation, disruption of membrane integrity, and impaired neurotransmission and neurotoxicity. Girls with ASD have disruption of ether/non-ether phospholipid balance in the MMG plasma that is similar to that found in other neurodevelopmental disorders. ASD boys in the CB analyses had the highest number of dysregulated chemical clusters. Machine learning classifiers distinguished ASD cases from controls with area under the receiver operating characteristic (AUROC) values ranging from 0.710 to 0.853. Predictive performance was better in CB analyses than in MMG. These findings may provide new insights into the sex-specific differences in ASD and have implications for discovery of biomarkers that may enable early detection and intervention.

Associations of types of grains and lifestyle with all-cause mortality among Chinese adults aged 65 years or older: a prospective cohort study.

BACKGROUND: Little is known on the association of types of grains with mortality and the moderating effect of lifestyle on this association. This study aims to evaluate the single or joint associations of types of grains and lifestyle with all-cause mortality among Chinese older adults. METHODS: Data were derived from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 1998 to 2018. Subjects aged ≥ 65 years were eligible. The types of grains included wheat, total rice, and coarse cereals. Lifestyle was derived using smoking, alcohol consumption, physical activity, and dietary pattern. All-cause mortality was the primary outcome. RESULTS: This study included 30275 participants with a mean age 87 ± 11 years and documented 19261 deaths during a mean follow-up of 4.8 years. Compared to wheat, in those with healthy and intermediate lifestyle, total rice was associated with a 13% (HR: 0.87, 95% CI 0.80, 0.93) and 6% (HR: 0.94, 95% CI 0.90, 1.00) lower risk of mortality, respectively, and coarse cereals were associated with a 14% (HR: 0.86, 95% CI 0.74, 1.00) and 12% (HR: 0.88, 95% CI 0.79, 0.97) lower risk of mortality, respectively. Meanwhile, an increase per SD in intakes of wheat and coarse cereals was associated with a 10% (HR: 1.10, 95% CI 1.03, 1.18) and 25% (HR: 1.25, 95% CI 1.08, 1.44) higher mortality rate in those with healthy lifestyle, and a 13% (HR: 1.13, 95% CI 1.08, 1.19) and 29% (HR: 1.29, 95% CI 1.17, 1.44) higher mortality in females but not males. In addition, a U-shaped association of intake of total grains with all- cause mortality was observed (P for non-linearity = 0.002), and a J-shaped association of intake of total rice with all- cause mortality was observed (P for non-linearity = 0.003). CONCLUSIONS: Specific types of grains and lifestyle were separately or jointly associated with all-cause mortality. Compared to wheat, total rice and coarse cereals were advanced grains for participants with a relatively healthy lifestyle. Intake of total rice was related to all-cause mortality in a dose-response manner. Therefore, a combination of intermediate intake of total rice and healthy lifestyle should be encouraged in older adults.

Remain or return? An empirical study of influencing factors on the return of Chinese international students during the COVID-19 pandemic.

Background: COVID-19 is now a global public health crisis with unprecedented political, economic, and social consequences affecting nations across the world. It also has a profound impact on the mobility of international students. When the COVID-19 was under control in China, and it was spreading dramatically in the United Kingdom, Chinese international students studying in the United Kingdom have been caught in a double bind over whether to return home or not. Objective: This study aims to explore the factors that influenced Chinese international students' choices of return during the COVID-19 pandemic when the COVID-19 was under control in China, while it was spreading dramatically in the United Kingdom. Methods: Taking Chinese international students studying in the United Kingdom as an empirical case, this study used qualitative and quantitative research methods to explore the factors that influenced their choices of return. Based on the Rational Choice Theory and qualitative analysis of text data, this paper constructed the influencing factors model of returning to China. On this basis, we developed a questionnaire and collected data from 1,333 students in late April and early May 2020. Binary Logistic Regression with 95% CI for odds ratio (OR) was used to identify significant factors. Results: The reserve of epidemic prevention supplies (OR = 0.712), transportation expenses (OR = 0.618), and quarantine expenses (OR = 0.702) negatively affected the return choice of overseas students. The supply of daily necessities (OR = 1.495), the anti-epidemic policy of the United Kingdom (OR = 1.684), and the demand for job hunting after graduation (OR = 1.661) had positive effects. Conclusion: The institutional rationality had the biggest promoting effect, replaced development rationality, and became the most important factor for overseas students to return to China during the COVID-19 pandemic. Economic rationality, which has a significant negative effect, is the biggest obstacle to returning home. These conclusions have policy implications for governments' response to the COVID-19 epidemic and improvement of the quality of services for overseas students.

Single-cell RNA sequencing combined with whole exome sequencing reveals the landscape of the immune pathogenic response to chronic mucocutaneous candidiasis with STAT1 GOF mutation.

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections with Candida of the skin, nails, and mucous membranes (e.g., mouth, esophagus, and vagina). Compared with that of other infectious diseases, the immune pathogenic mechanism of CMC is still poorly understood. We identified a signal transducer and activator of transcription 1 gain-of-function (c.Y289C) mutation in a CMC patient. Single-cell transcriptional profiling on peripheral blood mononuclear cells from this patient revealed decreases in immature B cells and monocytes. Further analysis revealed several differentially expressed genes related to immune regulation, including RGS1, TNFAIP3, S100A8/A9, and CTSS. In our review of the literature on signal transducer and activator of transcription 1 gain-of-function (c.Y289C) mutations, we identified seven cases in total. The median age of onset for CMC (n=4, data lacking for three cases) was 10.5 years (range: birth to 11 years), with an average onset age of 8 years. There were no reports linking tumors to the c.Y289C mutation, and the incidence of pre-existing clinical disease in patients with the c.Y289C mutation was similar to previous data.

Performance enhancement of deep-ultraviolet LEDs by using quaternary AlInGaN polarization-engineered multiple-symmetrical-stair quantum barriers without electron blocking layer.

In this paper, a structure design using quaternary AlInGaN as multiple-symmetrical-stair-shaped quantum barriers without an electron blocking layer is shown. The results show this design mitigates the droop effect to ∼0.1%, and the internal quantum efficiency reaches about 93.4%. It is believed that the better performance results from balanced electron and hole concentration and distribution of the current among the quantum wells, along with reduced non-radiative recombination. This work may be useful in the application of using quaternary AlInGaN materials as quantum barrier layers with computational simulations to design structures with electron-barrier-free layers.

Preferential subcortical collateral projections of pedunculopontine nucleus-targeting cortical pyramidal neurons revealed by brain-wide single fiber tracing.

The pedunculopontine nucleus (PPN) is a heterogeneous midbrain structure involved in various brain functions, such as motor control, learning, reward, and sleep. Previous studies using conventional tracers have shown that the PPN receives extensive afferent inputs from various cortical areas. To examine how these cortical axons make collateral projections to other subcortical areas, we used a dual-viral injection strategy to sparsely label PPN-targeting cortical pyramidal neurons in CaMKIIα-Cre transgenic mice. Using a high-speed volumetric imaging with on-the-fly-scan and Readout (VISoR) technique, we visualized brain-wide axonal projections of individual PPN-targeting neurons from several cortical areas, including the prelimbic region (PL), anterior cingulate area (ACA) and secondary motor cortex (MOs). We found that each PPN-projecting neuron had a unique profile of collateralization, with some subcortical areas being preferential targets. In particular, PPN-projecting neurons from all three traced cortical areas exhibited common preferential collateralization to several nuclei, with most neurons targeting the striatum (STR), lateral hypothalamic area (LHA) and periaqueductal gray (PAG), and a substantial portion of neurons also targeting the zona incerta (ZI), median raphe nucleus (MRN) and substantia nigra pars reticulata (SNr). Meanwhile, very specific collateralization patterns were found for other nuclei, including the intermediate reticular nucleus (IRN), parvicellular reticular nucleus (PARN) and gigantocellular reticular nucleus (GRN), which receive collateral inputs almost exclusively from the MOs. These observations provide potential anatomical mechanisms for cortical neurons to coordinate the PPN with other subcortical areas in performing different physiological functions.

Mir 135a inhibits tumor cell proliferation by regulating the expression of notch pathway in hepatoblastoma.

MiRNA affects the proliferation, migration and cycle of tumor cells. However, the mechanism of regulating Notch pathway expression and inhibiting tumor cell proliferation in hepatoblastoma is not clear, we need to further explore. In this study, the dact2 gene can inhibit liver fibrosis. In this experiment, we used in vitro culture of hepatoblastoma cells and flow cytometry to detect the effect of miRNA-135a on the tumor cell cycle. The expression of miRNA-135a was detected by real-time PCR in 6 tumor samples and normal controls to observe and analyze the expression level of the important signal pathway proteins in the cells after mir-135a transfection. The cells were divided into the experimental group and the control group. The experimental group was transfected with miRNA-135a cells, while the control group was not transfected. Finally, the data are analyzed and discussed. from the third day, the activity of M17 cells in the mir-135a group began to be inhibited. By the fifth day, the inhibition rate of M17 was 50.64% (P < 0.01), and M21 was 25.02% (P < 0.01). In the experimental group, 53.38% of the cells were in the G1 phase, and mir-135a could block the tumor cells in G1 phase, affect the cell cycle process, and then affect cell proliferation.