Femtosecond laser direct nanolithography of perovskite hydration for temporally programmable holograms.

Modern nanofabrication technologies have propelled significant advancement of high-resolution and optically thin holograms. However, it remains a long-standing challenge to tune the complex hologram patterns at the nanoscale for temporal light field control. Here, we report femtosecond laser direct lithography of perovskites with nanoscale feature size and pixel-level temporal dynamics control for temporally programmable holograms. Specifically, under tightly focused laser irradiation, the organic molecules of layered perovskites (PEA)2PbI4 can be exfoliated with nanometric thickness precision and subwavelength lateral size. This creates inorganic lead halide capping nanostructures that retard perovskite hydration, enabling tunable hydration time constant. Leveraging advanced inverse design methods, temporal holograms in which multiple independent images are multiplexed with low cross talk are demonstrated. Furthermore, cascaded holograms are constructed to form temporally holographic neural networks with programmable optical inference functionality. Our work opens up new opportunities for tunable photonic devices with broad impacts on holography display and storage, high-dimensional optical encryption and artificial intelligence.

Effects of graphene oxide and graphene quantum dots on enhancing CPP-ACP anti-caries ability of enamel lesion in a biofilm-challenged environment.

OBJECTIVE: To investigate the anticaries effects of graphene oxide (GO) and graphene quantum dots (GQDs) combined with casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on enamel in a biofilm-challenged environment. MATERIAL AND METHODS: GO and GQDs were synthesised using citric acid. The antibiofilm and biofilm inhibition effects for Streptococcus mutans were evaluated by scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and colony-forming units (CFU). Remineralisation ability was determined by assessing mineral loss, calcium-to-phosphorus ratio, and surface morphology. To create a biofilm-challenged environment, enamel blocks were immersed in S. mutans to create the lesion and then subjected to artificial saliva/biofilm cycling for 7 days. Anticaries effects of GO, GQDs, GQDs@CPP-ACP, GO@CPP-ACP, and CPP-ACP were determined by broth pH and mineral changes after 7-day pH cycling. Biocompatibility was tested using a Cell Counting Kit-8 (CCK8) assay for human gingival fibroblasts (HGF-1). RESULTS: GQDs and GO presented significant antibiofilm and biofilm inhibition effects compared to the CPP-ACP and control groups (P < 0.05). The enamel covered by GQDs and GO showed better crystal structure formation and less mineral loss (P < 0.05) than that covered by CPP-ACP alone. After 7 days in the biofilm-challenged environment, the GO@CPP-ACP group showed less lesion depth than the CPP-ACP and control groups (P < 0.05). GO and GQDs showed good biocompatibility compared to the control group by CCK8 (P > 0.05) within 3 days. CONCLUSION: GO and GQDs could improve the anti-caries effects of CPP-ACP, and CPP-ACP agents with GO or GQDs could be a potential option for enamel lesion management. CLINICAL SIGNIFICANCE: GO and GQDs have demonstrated the potential to significantly enhance the anticaries effects of CPP-ACP. Incorporating these nanomaterials into CPP-ACP formulations could provide innovative and effective options for the management of enamel lesions, offering improved preventive and therapeutic strategies in dental care.

Multimodal Artificial Synapses for Neuromorphic Application.

The rapid development of neuromorphic computing has led to widespread investigation of artificial synapses. These synapses can perform parallel in-memory computing functions while transmitting signals, enabling low-energy and fast artificial intelligence. Robots are the most ideal endpoint for the application of artificial intelligence. In the human nervous system, there are different types of synapses for sensory input, allowing for signal preprocessing at the receiving end. Therefore, the development of anthropomorphic intelligent robots requires not only an artificial intelligence system as the brain but also the combination of multimodal artificial synapses for multisensory sensing, including visual, tactile, olfactory, auditory, and taste. This article reviews the working mechanisms of artificial synapses with different stimulation and response modalities, and presents their use in various neuromorphic tasks. We aim to provide researchers in this frontier field with a comprehensive understanding of multimodal artificial synapses.

Effects of Limosilactobacillus reuteri strains PTA-126787 and PTA-126788 on intestinal barrier integrity and immune homeostasis in an alcohol-induced leaky gut model.

Intestinal barrier is a first line of defense that prevents entry of various harmful substances from the lumen into the systemic environment. Impaired barrier function with consequent translocation of harmful substances into systemic circulation ("leaky gut") is a central theme in many gastrointestinal, autoimmune, mental, and metabolic diseases. Probiotics have emerged as a promising strategy to maintain intestinal integrity and address "leaky gut". Using in silico, in vitro and avian in vivo analyses, we previously showed that two novel L. reuteri strains, PTA-126787 (L. reuteri 3630) and PTA-126788 (L. reuteri 3632), isolated from broiler chickens possess favorable safety profiles. Consistent with a recent study, here we show that L. reuteri 3630 and 3632 are phylogenetically similar to human L. reuteri strains. Daily administration of high doses of L. reuteri 3630 and 3632 to Sprague Dawley rats for 28 days was found to be safe with no adverse effects. More importantly, administration of L. reuteri 3630 and 3632 significantly reduced markers associated with alcohol-induced leaky gut, by downregulating inflammatory cytokines and upregulating anti-inflammatory cytokines in an alcohol model of leaky gut in mice. While L. reuteri 3630 cells and supernatant showed no activation, L. reuteri 3632 cells but not supernatant showed activation of AhR, a key transcription factor that regulates gut and immune homeostasis. L. reuteri 3630 is creamish white in morphology typical of Lactobacillus species and L. reuteri 3632 displays a unique orange pigmentation, which was stable even after passaging for 480 generations. We identified a rare polyketide biosynthetic gene cluster in L. reuteri 3632 that likely encodes for the orange-pigmented secondary metabolite. Similar to L. reuteri 3632 cells, the purified orange metabolite activated AhR. All together, these data provide evidence on the phylogenetic relatedness, safety, efficacy, and one of the likely mechanisms of action of L. reuteri 3630 and 3632 for potential probiotic applications to address "leaky gut" and associated pathologies in humans.

Comprehensive research on the properties of advanced glycation end products in food and biological samples and their harmful role in inducing metabolic diseases.

Advanced glycation end products (AGEs) are formed by the Maillard reaction, a nonenzymatic process that occurs widely in cooking, food processing, and within the human body. Primarily, AGEs are formed by the glycation of reducing sugars with amino groups, and this process is heat-dependent. With changes in lifestyle, there has been an increase in the diversity of dietary habits, including those patterns associated with Western diets, which include the consumption of processed foods that are rich in AGEs. Excessive intake and exposure to AGEs are known to cause abnormalities in body function such as obesity, diabetes, and fatty liver, and the beneficial effects of AGEs in food processing in improving food flavor and quality. To obtain meaningful data regarding AGEs in a variety of food and human samples, it is necessary to more precisely characterize and analyze the AGEs extracted from samples to obtain accurate results. This review explores the recent analytical research and characterization of AGEs in foods, including casein, ß-lactoglobulin, soy protein, and meat protein, and in human samples, such as glycated-albumin, hemoglobin, and plasma. Additionally, it explores the metabolic fate of AGEs in the body and the mechanisms of disease associated with metabolic abnormalities that may be caused by the consumption of foods containing AGEs. This review aims to provide an overview of the perspectives of relevant recent and future research on metabolic abnormalities caused by foods containing AGEs or by AGEs produced in the body.

Interventions to prevent mother-to-child transmission in breastfeeding mothers with HIV: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to systematically review interventions to prevent mother-to-child transmission of HIV during breastfeeding. We conducted a systematic review and meta-analysis using specific criteria to identify randomized controlled trials that focused on pregnant and breastfeeding women living with HIV and their children from birth to 2 years of age. We extensively searched electronic databases, including Web of Science, Scopus, PubMed, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Google Scholar up to October 24, 2023. After screening 3,110 titles and abstracts, we reviewed 306 full texts. Of these, we assessed the quality and risk of bias of fifty-five articles, ultimately identifying seven studies. Four of these studies, which focused on antiretroviral therapy (ART), were included in the meta-analysis. There was little heterogeneity in study methodology and pooled estimates. The postnatal HIV transmission rate was found to be 0.01 (95%CI: 0.00 - 0.02). Therefore, the risk of mother-to-child transmission among breastfeeding mothers with HIV was significantly lower in the intervention groups than in the placebo groups. Analysis of funnel plots and Egger's test (p = 0.589) showed no evidence of publication bias. In addition to the four articles, two studies compared different ART regimens and one study compared the administration of high-dose vitamin A to the mother or the child. The results suggest that the use of ART significantly reduces the risk of postnatal HIV transmission compared with placebo. However, the effectiveness of different ART regimens or other therapies, including high-dose vitamin A, is unclear.

Decrease in UCP1 by sustained high lipid promotes NK cell necroptosis to exacerbate nonalcoholic liver fibrosis.

Uncoupling protein 1 (UCP1) catalyzes the leak of protons across the mitochondrial inner membrane for thermogenesis. Compromised NK cell activity is involved in the occurrence of nonalcoholic liver fibrosis. Here, decreased UCP1 in NK cells was identified in patients with advanced nonalcoholic fatty liver disease. Although no obvious changes were observed in the NK cells of physiologic UCP1-/- mice (8-10 weeks old), impaired NK cell bioactivity was shown in methionine-choline-diet (MCD)-fed UCP1-/- mice and involved in the acerbation of nonalcoholic steatohepatitis (NASH) progress to liver fibrosis. Moreover, UCP1-deficient NK cells were responsible for the aggravation of liver fibrosis, as confirmed in MCD-fed UCP1flox/flox-NCR1cre mice. Acerbation of liver fibrosis was also seen in wild-type mice when their endogenous NK cells were replaced with UCP1-/- NK cells. Transcriptions of mitophagy-associated molecules in UCP1-/- NK cells were enhanced according to RNA-seq. Electron microscopic results showed mitochondrial injuries and autophagic vesicles in MCD-fed NKWT cells, PA-treated NKWT cells, or physiologic NKKO cells. However, the co-existence of UCP1 deficiency and high lipid can synergistically induce NK cell necroptosis via DRP1S616 accompanied with reduced mitophagy. Finally, The UCP1 in NK cells was downregulated when treated by sustained high PA (600 µM) via the PPARγ/ATF2 axis. Thus, persistent high-lipid treatment not only decreases UCP1 expression but also combines with reduced UCP1 to promote NK cell necroptosis, and it is involved in NASH progression to fibrosis.

ROS responsive hydrogel for inhibition of MUC5AC against allergic rhinitis: A new delivery strategy for Ipratropium Bromide.

Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa mediated by immunoglobulin E (IgE) after exposure to allergens. The bothersome symptoms of AR, such as runny nose and nasal congestion, affect millions of people worldwide. Ipratropium Bromide (IB), commonly used in clinical practice for treating AR, requires frequent administration through nasal spray and may cause significant irritation to the nasal mucosa. The induction of ROS is closely related to the initiation and symptoms of AR, and ROS will continue to accumulate during the onset of AR. To address these challenges, we have designed a drug delivery system that can be administered in liquid form and rapidly crosslink into a ROS-responsive gel in the nasal cavity. This system enables sustained ROS responsive release of IB in a high-concentration ROS environment at AR lesions, thereby alleviating AR symptoms. The gel demonstrated prolonged release of IB for up to 24 hours in rats. In the treatment of AR rat models, it improved their symptoms, reduced the expression of various inflammatory factors, suppressed MUC5AC protein expression, and decreased mucus secretion through a ROS responsive IB release pattern. Overall, this system holds promise as a better option for AR treatment and may inspire the design of nanogel-based nasal drug delivery systems.

Lindera obtusiloba Blume Alleviates Non-Alcoholic Fatty Liver Disease Promoted by Nε-(carboxymethyl)lysine.

Non-alcoholic fatty liver disease (NAFLD) is a major issue because it is closely associated with metabolic diseases. Advanced glycation end products (AGEs) are implicated as risk factors for steatosis during NAFLD progression. AGEs influence NAFLD progression through a receptor-independent pathway involving AGE cross-link formation and a receptor-dependent pathway that binds to receptors like receptors for advanced glycation end products (RAGE). The objectives of this study are to examine the effect of Lindera obtusiloba Blume (LO) on NAFLD promoted by Nε-(carboxymethyl)lysine (CML), one of the most common dietary AGEs. The anti-glycation effects of LO were evaluated by inhibiting the AGEs formation and AGEs-collagen cross-links breaking. The efficacy of LO against NAFLD promoted by CML was assessed using both in vitro and in vivo models. NAFLD was induced in mice by feeding a high-fat diet and orally administering CML over a period of 12 weeks, and the effects of LO on lipid metabolism and its regulatory mechanisms were investigated. LO showed the effect of inhibited AGEs formation and breakage, and collagen cross-linking. Fed a high-fat diet with administered CML by gavage, LO administration resulted in a reduction in body weight, fat mass, serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels. LO reduced hepatic CML accumulation and RAGE expression in mice fed a high-fat diet and orally administered CML. LO alleviated hepatic steatosis accompanied by lipid accumulation and histological damage by suppressing the expression of sterol regulatory element-binding protein 1c, carbohydrate response element binding protein, fatty acid synthase, stearoyl-CoA desaturase1, tumor necrosis factor-α, and interleukin-1ß. LO alleviated the MAPK/NF-κB expression by attenuating CML and RAGE expression. Taken together, our results demonstrate that LO alleviates the progression of NAFLD by lowering the levels of AGEs by downregulating CML/RAGE expression.

Machine Learning Algorithms for the Diagnosis of Class III Malocclusions in Children.

Artificial intelligence has been applied to medical diagnosis and decision-making but it has not been used for classification of Class III malocclusions in children. OBJECTIVE: This study aims to propose an innovative machine learning (ML)-based diagnostic model for automatically classifies dental, skeletal and functional Class III malocclusions. METHODS: The collected data related to 46 cephalometric feature measurements from 4-14-year-old children (n = 666). The data set was divided into a training set and a test set in a 7:3 ratio. Initially, we employed the Recursive Feature Elimination (RFE) algorithm to filter the 46 input parameters, selecting 14 significant features. Subsequently, we constructed 10 ML models and trained these models using the 14 significant features from the training set through ten-fold cross-validation, and evaluated the models' average accuracy in test set. Finally, we conducted an interpretability analysis of the optimal model using the ML model interpretability tool SHapley Additive exPlanations (SHAP). RESULTS: The top five models ranked by their area under the curve (AUC) values were: GPR (0.879), RBF SVM (0.876), QDA (0.876), Linear SVM (0.875) and L2 logistic (0.869). The DeLong test showed no statistical difference between GPR and the other models (p > 0.05). Therefore GPR was selected as the optimal model. The SHAP feature importance plot revealed that he top five features were SN-GoMe (the ratio of the length of the anterior skull base SN to that of the mandibular base GoMe), U1-NA (maxillary incisor angulation to NA plane), Overjet (the distance between two lines perpendicular to the functional occlusal plane from U1 and L), ANB (the difference between angles SNA and SNB), and AB-NPo (the angle between the AB and N-Pog line). CONCLUSIONS: Our findings suggest that ML models based on cephalometric data could effectively assist dentists to classify dental, functional and skeletal Class III malocclusions in children. In addition, features such as SN_GoMe, U1_NA and Overjet can as important indicators for predicting the severity of Class III malocclusions.

Myricetin mitigates motor disturbance and decreases neuronal ferroptosis in a rat model of Parkinson's disease.

Ferroptosis is an iron-dependent cell death form characterized by reactive oxygen species (ROS) overgeneration and lipid peroxidation. Myricetin, a flavonoid that exists in numerous plants, exhibits potent antioxidant capacity. Given that iron accumulation and ROS-provoked dopaminergic neuron death are the two main pathological hallmarks of Parkinson's disease (PD), we aimed to investigate whether myricetin decreases neuronal death through suppressing ferroptosis. The PD models were established by intraperitoneally injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into rats and by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP+), respectively. Ferroptosis was identified by assessing the levels of Fe2+, ROS, malondialdehyde (MDA), and glutathione (GSH). The results demonstrated that myricetin treatment effectively mitigated MPTP-triggered motor impairment, dopamine neuronal death, and α-synuclein (α-Syn) accumulation in PD models. Myricetin also alleviated MPTP-induced ferroptosis, as evidenced by decreased levels of Fe2+, ROS, and MDA and increased levels of GSH in the substantia nigra (SN) and serum in PD models. All these changes were reversed by erastin, a ferroptosis activator. In vitro, myricetin treatment restored SH-SY5Y cell viability and alleviated MPP+-induced SH-SY5Y cell ferroptosis. Mechanistically, myricetin accelerated nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and subsequent glutathione peroxidase 4 (Gpx4) expression in MPP+-treated SH-SY5Y cells, two critical inhibitors of ferroptosis. Collectively, these data demonstrate that myricetin may be a potential agent for decreasing dopaminergic neuron death by inhibiting ferroptosis in PD.

Left Bundle Branch Area Pacing With or Without Conduction System Capture in Heart Failure Models.

BACKGROUND: Left bundle branch area pacing includes left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP), which is effective in patients with dyssynchronous heart failure (DHF). However, the basic mechanisms are unknown. OBJECTIVES: This study aimed to compare LBBP with LVSP and explore potential mechanisms underlying the better clinical outcomes of LBBP. METHODS: A total of 24 beagles were assigned to the following groups: 1) control group; 2) DHF group, left bundle branch ablation followed by 6 weeks of AOO pacing at 200 ppm; 3) LBBP group, DHF for 3 weeks followed by 3 weeks of DOO pacing at 200 ppm; and 4) LVSP with the same interventions in the LBBP group. Metrics of electrocardiogram, echocardiography, hemodynamics, and expression of left ventricular proteins were evaluated. RESULTS: Compared with LVSP, LBBP had better peak strain dispersion (44.67 ± 1.75 ms vs 55.50 ± 4.85 ms; P < 0.001) and hemodynamic effect (dP/dtmax improvement: 27.16% ± 7.79% vs 11.37% ± 4.73%; P < 0.001), whereas no significant differences in cardiac function were shown. The altered expressions of proteins in the lateral wall vs septum in the DHF group were partially reversed by LBBP and LVSP, which was associated with the contraction and adhesion process, separately. CONCLUSIONS: The animal study demonstrated that LBBP offered better mechanical synchrony and improved hemodynamics than LVSP, which might be explained by the reversed expression of contraction proteins. These results supported the potential superiority of left bundle branch area pacing with the capture of the conduction system in DHF model.

Discovery of GPR84 Fluorogenic Probes Based on a Novel Antagonist for GPR84 Bioimaging.

GPR84 is a promising therapeutic target and biomarker for a range of diseases. In this study, we reported the discovery of BINOL phosphate (BINOP) derivatives as GPR84 antagonists. By investigating the structure-activity relationship, we identified 15S as a novel GPR84 antagonist. 15S exhibits low nanomolar potency and high selectivity for GPR84, while its enantiomer 15R is less active. Next, we rationally designed and synthesized a series of GPR84 fluorogenic probes by conjugating Nile red and compound 15S. The leading hybrid, probe F8, not only retained GPR84 activity but also exhibited low nonspecific binding and a turn-on fluorescent signal in an apolar environment. F8 enabled visualization and detection of GPR84 in GPR84-overexpressing HEK293 cells and lipopolysaccharide-stimulated neutrophils. Furthermore, we demonstrated that F8 can detect upregulated GPR84 protein levels in mice models of inflammatory bowel disease and acute lung injury. Thus, compound F8 represents a promising tool for studying GPR84 functions.

Amino acid mutations PB1-V719M and PA-N444D combined with PB2-627K contribute to the pathogenicity of H7N9 in mice.

H7N9 subtype avian influenza viruses (AIVs) cause 1567 human infections and have high mortality, posing a significant threat to public health. Previously, we reported that two avian-derived H7N9 isolates (A/chicken/Eastern China/JTC4/2013 and A/chicken/Eastern China/JTC11/2013) exhibit different pathogenicities in mice. To understand the genetic basis for the differences in virulence, we constructed a series of mutant viruses based on reverse genetics. We found that the PB2-E627K mutation alone was not sufficient to increase the virulence of H7N9 in mice, despite its ability to enhance polymerase activity in mammalian cells. However, combinations with PB1-V719M and/or PA-N444D mutations significantly enhanced H7N9 virulence. Additionally, these combined mutations augmented polymerase activity, thereby intensifying virus replication, inflammatory cytokine expression, and lung injury, ultimately increasing pathogenicity in mice. Overall, this study revealed that virulence in H7N9 is a polygenic trait and identified novel virulence-related residues (PB2-627K combined with PB1-719M and/or PA-444D) in viral ribonucleoprotein (vRNP) complexes. These findings provide new insights into the molecular mechanisms underlying AIV pathogenesis in mammals, with implications for pandemic preparedness and intervention strategies.

Dietary fishmeal replacement by Clostridium autoethanogenum protein meal influences the nutritional and sensory quality of turbot (Scophthalmus maximus) via the TOR/AAR/AMPK pathways.

Clostridium autoethanogenum protein (CAP) is a promising protein source for aquaculture; however, how CAP influences fish quality is worth extensive research. We randomly allocated 630 turbot with initial body weights of about 180 g into 6 groups, with fishmeal-based control diet or diet with CAP replacing 15% (CAP15), 30% (CAP30), 45% (CAP45), 60% (CAP60), or 75% (CAP75) of fishmeal protein. After a 70-d feeding trial, the fillet yield (P = 0.015) and content of protein (P = 0.017), collagen (P < 0.001), hydroxyproline (P < 0.001), C20:5n-3 (P = 0.007), and ∑n-3/∑n-6 polyunsaturated fatty acids ratio (P < 0.001) in turbot muscle was found to decrease linearly with increasing CAP. However, turbot fed CAP15 diet maintained these parameters (P > 0.05). By contrast, the muscle hardness increased linearly with increasing CAP (P = 0.004), accompanied by linear reduction of muscle fiber area (P = 0.003) and expression of myogenesis-related genes, including cathepsin D (ctsd P < 0.001) and muscle ring finger protein 1 (murf 1, P < 0.001). Phosphorylation of protein kinase B (Akt, P < 0.001), target of rapamycin (TOR, P = 0.001), eukaryotic initiation factor 4E-binding protein 1 (4E-BP1, P < 0.001), and ribosomal protein S6 (S6, P < 0.001) decreased linearly; however, phosphorylation of AMP-activated protein kinase (AMPK, P < 0.001), eukaryotic initiation factor 2α (eIF2α, P < 0.001), and the abundance of activating transcription factor 4 (ATF4, P < 0.001) increased with increasing CAP, suggesting that the TOR signaling pathway was inhibited, and the amino acid response (AAR) and AMPK pathways were activated. Additionally, expression of genes related to protein degradation, including myogenic factor 5 (myf 5, P < 0.001), myogenic differentiation (myod, P < 0.001), paired box 7 (pax 7, P < 0.001), and ctsd (P < 0.001), decreased linearly with increasing CAP. In conclusion, CAP could be used to replace up to 15% of fishmeal without negatively impacting turbot quality. However, higher levels of CAP decreased fillet yield, muscle protein content, and muscle fiber diameter while increasing muscle hardness, which could be attributed to the inhibition of the TOR pathway and activation of the AAR and AMPK pathways.

The combined association of physical activity and alcohol use with long-term mortality: an age-stratified analysis.

BACKGROUND: The combined association of physical activity (PA) and alcohol use (AU) with long-term mortality is yet to be investigated. METHODS: For the current study, 12,621 participants aged ≥ 20 years were enrolled from the National Health and Nutrition Examination Survey (1999-2004). The study endpoint was all-cause mortality. Cox proportional hazards regression models were used to examine the combined effect of PA and AU on long-term mortality. RESULTS: The study population was divided into young (< 60 years, N = 8,258) and old (≥ 60 years, N = 4,363) groups. The median follow-up time was 203 months. In both young and old group, sedentary lifestyle combined with even minimal AU were associated with elevated risk of death (all P < 0.05). In young group, the integration of high volume AU with any degree of PA, including sedentary PA (HR = 2.35, 95% CI 1.24-4.44, P = 0.009), low PA (HR = 1.64, 95% CI 1.01-2.68, P = 0.047), and moderate-to-vigorous PA (HR = 1.99, 95% CI 1.03-3.84, P = 0.041), was associated with an increased risk of mortality. This relationship persisted as significant after adjusting for potential confounders (all P < 0.05). In old group, combining moderate-to-vigorous PA and low volume AU (HR = 0.59, 95% CI 0.37-0.94, P = 0.027) was associated with a reduction in mortality. After adjustment, the combination of moderate-to-vigorous PA and low volume AU was independently associated with favorable prognostic outcomes (all P < 0.05). CONCLUSIONS: In both age groups, combining sedentary lifestyle with even minimal AU was a risk factor for death. In young group, combining any level of PA with high volume AU was associated with increased mortality. In old group, combining moderate-to-vigorous PA with low volume AU was related to reduced mortality.

Achromatic CMOS-Integrated Four-Bit Orbital Angular Momentum Mode Detector at Three Wavelengths.

The simultaneous detection of the orbital angular momentum (OAM) and wavelength offers new opportunities for optical multiplexing. However, because of the dispersion of lens functions for Fourier transformation, the mode conversions at distinct wavelengths cannot be achieved in the same plane. Here we propose an ultracompact achromatic complementary metal oxide semiconductor (CMOS)-integrated OAM mode detector. Specifically, a spatial multiplexed scheme, randomly interleaving the phase distributions for distributing the superposed OAM modes into preset positions at distinct wavelengths, is presented. In addition, such a nanoprinted achromatic OAM detector featuring a microscale size and a short focal length can be integrated onto a CMOS chip. Consequently, the four-bit incident light beams at three discrete wavelengths (633, 532, and 488 nm) can be distinguished with a high degree of accuracy evaluated by the average standardized Euclidean distance of ∼0.75 between the analytical and target results. Our results showcase a miniaturized platform for achieving high-capacity information processing.

Myeloid-derived suppressor cells in the tumor microenvironment reduce uncoupling protein 1 expression to boost immunosuppressive activity.

Uncoupling protein 1 (UCP1) is located at the inner membrane of mitochondria and mediates nonshivering thermogenesis. Its abnormal expression is associated with metabolic diseases, cancer, and acute kidney injury. Myeloid-derived suppressor cells (MDSCs) with immunosuppressive activity accumulate in the tumor microenvironment (TME). Here, decreased UCP1 expression in MDSCs was observed in the peripheral blood of patients with colorectal cancer and transplanted mouse tumors. Aggravated tumor progression was observed in UCP1-knockout mice and conditional knockout mice (UCP1fl/fl-S100A8cre). The number of G-MDSCs and M-MDSCs increased in the transplanted tumor tissues from UCP1-deficient mice compared with those from wild-type mice. The tumor-promoting effect disappeared when the tumor-bearing mice were depleted of MDSCs by the α-DR5 administration. Adoptive transfer of tumor-derived MDSCs sharply promoted the tumor growth in vivo. Furthermore, these tumor-derived MDSCs enhanced the proliferation, reduced death, inhibited IFN-γ production of CD4+ and CD8+T cells, and induced Treg cells ex vivo. In conclusion, MDSCs in the TME alter the metabolic pattern by decreasing UCP1 expression to enhance immunosuppressive activity for tumor escape.

Multimodal deep learning using on-chip diffractive optics with in situ training capability.

Multimodal deep learning plays a pivotal role in supporting the processing and learning of diverse data types within the realm of artificial intelligence generated content (AIGC). However, most photonic neuromorphic processors for deep learning can only handle a single data modality (either vision or audio) due to the lack of abundant parameter training in optical domain. Here, we propose and demonstrate a trainable diffractive optical neural network (TDONN) chip based on on-chip diffractive optics with massive tunable elements to address these constraints. The TDONN chip includes one input layer, five hidden layers, and one output layer, and only one forward propagation is required to obtain the inference results without frequent optical-electrical conversion. The customized stochastic gradient descent algorithm and the drop-out mechanism are developed for photonic neurons to realize in situ training and fast convergence in the optical domain. The TDONN chip achieves a potential throughput of 217.6 tera-operations per second (TOPS) with high computing density (447.7 TOPS/mm2), high system-level energy efficiency (7.28 TOPS/W), and low optical latency (30.2 ps). The TDONN chip has successfully implemented four-class classification in different modalities (vision, audio, and touch) and achieve 85.7% accuracy on multimodal test sets. Our work opens up a new avenue for multimodal deep learning with integrated photonic processors, providing a potential solution for low-power AI large models using photonic technology.

Superconducting nanowire single-photon detector with polarization insensitivity, ultrafast response, and high efficiency.

This study proposed what we believe to be a novel method for fabricating superconducting nanowire single-photon detectors (SNSPDs) with high efficiency, polarization insensitivity, and ultrafast response. To achieve these properties in niobium nitride (NbN) SNSPDs, the periodic four-split rings (PFSR) were positioned above the nanowires. This design uses the localized surface plasmon resonance to enhance the electric field around nanowires. For an incident light with a wavelength of 1550 nm, the PFSR-SNSPD structure achieved a polarization extinction ratio of 1.0064 and absorptions of 88.94% and 88.37% under TE and TM polarizations, respectively. The nanowire length was reduced by 85% using a meandering nanowire arrangement with a fill factor of 0.074.