Clinical Significance of Sarcopenia in Elderly Patients Undergoing Endoscopic Submucosal Dissection: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: As global life expectancy rises and gastrointestinal tumor incidence increases, more elderly patients are undergoing endoscopic submucosal dissection (ESD) for tumor treatment. The current situation highlights the importance of sarcopenia assessment before ESD. This systematic review and meta-analysis aim to assess sarcopenia's role in predicting post-ESD adverse outcomes in the elderly. METHODS: We conducted a systematic review and meta-analysis to investigate the impact of sarcopenia on the prognosis of elderly patients undergoing ESD treatment. A comprehensive search was conducted across three databases (PubMed, Embase, Web of Science). We were using NEWCASTLE-OTTAWA ASSESSMENT SCALE for risk of bias assessment. The data were synthesized using Review Manager 5.3. RESULTS: A total of 9 reports were identified, analyzing 7 indicators, with a combined sample size of 6044. Through a series of analyses, we have derived several highly credible research findings: the overall OR and 95% CI for gastric and colorectal post-ESD perforation between sarcopenia and nonsarcopenia groups were 1.34 [0.92, 1.97], for CTCAE grade > 2 was 2.65 [1.45, 4.82], for upper gastrointestinal post-ESD pneumonia were 1.97 [1.30, 2.99], and for gastric post-ESD mortality within 5 years were 2.96 [1.33, 6.58]. CONCLUSIONS: Sarcopenia is a risk factor for increased incidence of complications (CTCAE > 2) after undergoing gastric and colorectal ESD, increased pneumonia rates, and higher mortality rates within five years following gastric ESD treatment in elderly patients. However, sarcopenia does not lead to an increased perforation rate in elderly patients undergoing gastric and colorectal ESD treatments. Registration and protocol: The protocol for this study was registered on the Open Science Framework in 2024 https://doi.org/10.17605/OSF.IO/7B2CZ . We also conducted pre-registration on PROSPERO (CRD42024532547).

Enhanced degradation of enrofloxacin in mariculture wastewater based on marine bacteria and microbial carrier.

This study aimed to isolate marine bacteria to investigate their stress response, inhibition mechanisms, and degradation processes under high-load conditions of salinity and enrofloxacin (ENR). The results demonstrated that marine bacteria exhibited efficient pollutant removal efficiency even under high ENR stress (up to 10 mg/L), with chemical oxygen demand (COD), total phosphorus (TP), total nitrogen (TN) and ENR removal efficiencies reaching approximately 88%, 83%, 61%, and 73%, respectively. The predominant families of marine bacteria were Bacillaceae (50.46%), Alcanivoracaceae (32.30%), and Rhodobacteraceae (13.36%). They responded to ENR removal by altering cell membrane properties, stimulating the activity of xenobiotic-metabolizing enzymes and antioxidant systems, and mitigating ENR stress through the secretion of extracellular polymeric substance (EPS). The marine bacteria exhibited robust adaptability to environmental factors and effective detoxification of ENR, simultaneously removing carbon, nitrogen, phosphorus, and antibiotics from the wastewater. The attapulgite carrier enhanced the bacteria's resistance to the environment. When treating actual mariculture wastewater, the removal efficiencies of COD and TN exceeded 80%, TP removal efficiency exceeded 90%, and ENR removal efficiency approached 100%, significantly higher than reported values in similar salinity reactors. Combining the constructed physical and mathematical models of tolerant bacterial, this study will promote the practical implementation of marine bacterial-based biotechnologies in high-loading saline wastewater treatment.

Synergistic Effect of Layered Double Hydroxides Nanodosage Form to Induce Apoptosis and Ferroptosis in Breast Cancer.

Background: Breast cancer is the most common cancer in women and one of the leading causes of cancer death worldwide. Ferroptosis, a promising mechanism of killing cancer cells, has become a research hotspot in cancer therapy. Simvastatin (SIM), as a potential new anti-breast cancer drug, has been shown to cause ferroptosis of cancer cells and inhibit breast cancer metastasis and recurrence. The purpose of this study is to develop a novel strategy boosting ferroptotic cascade for synergistic cancer therapy. Methods: In this paper, iron base form of layered double hydroxide supported simvastatin (LDHs-SIM) was synthesized by hydrothermal co-precipitation method. The characterization of LDHs-SIM were assessed by various analytical techniques, including ultraviolet-visible (UV-vis) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). Biological activity, ferroptosis mechanism and biocompatibility were analyzed through in vivo and in vitro analysis, so as to evaluate its therapeutic effect on breast cancer. Results: The constructed LDHs-SIM nanosystem can not only release SIM through mevalonate (MVA) pathway, inhibit the expression of glutathione peroxidase 4 (GPX4), inhibit the expression of SLC7A11 and reduce the synthesis efficiency of GSH, but also promote the accumulation of Fe2+ in cells through the release of Fe3+, and increase the intracellular ROS content. In addition, LDHs-SIM nanosystem can induce apoptosis of breast cancer cells to a certain extent, and achieve the synergistic effect of apoptosis and ferroptosis. Conclusion: In the present study, we demonstrated that nanoparticles of layered double hydroxides (LDHs) loaded with simvastatin were more effective than a free drug at inhibiting breast cancer cell growth, In addition, superior anticancer therapeutic effects were achieved with little systemic toxicity, indicating that LDHs-SIM could serve as a safe and high-performance platform for ferroptosis-apoptosis combined anticancer therapy.

Drug Screening and Validation Targeting TDP-43 Proteinopathy for Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) stands as a rare, yet severely debilitating disorder marked by the deterioration of motor neurons (MNs) within the brain and spinal cord, which is accompanied by degenerated corticobulbar/corticospinal tracts and denervation in skeletal muscles. Despite ongoing research efforts, ALS remains incurable, attributed to its intricate pathogenic mechanisms. A notable feature in the pathology of ALS is the prevalence of TAR DNA-binding protein 43 (TDP-43) proteinopathy, detected in approximately 97% of ALS cases, underscoring its significance in the disease's progression. As a result, strategies targeting the aberrant TDP-43 protein have garnered attention as a potential avenue for ALS therapy. This review delves into the existing drug screening systems aimed at TDP-43 proteinopathy and the models employed for drug efficacy validation. It also explores the hurdles encountered in the quest to develop potent medications against TDP-43 proteinopathy, offering insights into the intricacies of drug discovery and development for ALS. Through this comprehensive analysis, the review sheds light on the critical aspects of identifying and advancing therapeutic solutions for ALS.

Empagliflozin, a sodium-glucose cotransporter inhibitor enhancing mitochondrial action and cardioprotection in metabolic syndrome.

Metabolic syndrome (MetS) has a large clinical population nowadays, usually due to excessive energy intake and lack of exercise. During MetS, excess nutrients stress the mitochondria, resulting in relative hypoxia in tissues and organs, even when blood supply is not interrupted or reduced, making mitochondrial dysfunction a central pathogenesis of cardiovascular disease in the MetS. Sodium-glucose cotransporter 2 inhibitors were designed as a hyperglycemic drug that acts on the renal tubules to block sugar reabsorption in primary urine. Recently they have been shown to have anti-inflammatory and other protective effects on cardiomyocytes in MetS, and have also been recommended in the latest heart failure guidelines as a routine therapy. Among these inhibitors, empagliflozin shows better clinical promise due to less influence from glomerular filtration rate. This review focuses on the mitochondrial mechanisms of empagliflozin, which underlie the anti-inflammatory and recover cellular functions in MetS cardiomyocytes, including stabilizing calcium concentration, mediating metabolic reprogramming, maintaining homeostasis of mitochondrial quantity and quality, stable mitochondrial DNA copy number, and repairing damaged mitochondrial DNA.

Clinicopathological Characteristics and Risk Factors of Young-Onset Gastric Carcinoma: A Systematic Review and Meta-analysis.

INTRODUCTION: The characteristics of gastric carcinoma in young individuals differ from that in older individuals. We conducted a systematic review and meta-analysis to explore the clinicopathological features and risk factors associated with young-onset (younger than 50 years) gastric carcinoma. METHODS: We searched for studies published between January 1, 1990, and September 1, 2023, on patients with young-onset gastric carcinoma in PubMed, EMBASE, Web of Science, and MEDLINE to explore clinicopathological characteristics among this specific patient group. Extracted information included the proportion of patients with symptoms or family history of gastric cancer, tumor location, and histological features such as Lauren or World Health Organization histological classification and degree of differentiation. Additional analyses were conducted on risk factors such as positive family history, Helicobacter pylori infection, or high-risk nutritional or behavioral factors. The estimates were derived using random or fixed-effect models and included subgroup analyses based on different sex and age groups. This study was registered in PROSPERO (CRD42023466131). RESULTS: We identified 5,696 records, 1,292 were included in the quality assessment stage. Finally, 84 studies from 18 countries or regions including 89,447 patients with young-onset gastric carcinoma were included. Young-onset gastric carcinoma has slight female predominance (53.7%, 95% confidence interval [CI]: 51.6-55.7%), with most having symptoms (87.0%, 95% CI: 82.4%-91.7%). Family history was reported in 12.1% (95% CI: 9.5%-14.7%). H. pylori infection was detected in 60.0% of cases (95% CI: 47.1%-72.8%). Most of these carcinomas were in the non-cardia region (89.6%, 95% CI: 82.4%-96.8%), exhibiting Lauren diffuse-type histology (71.1%, 95% CI: 66.8%-75.3%) and poor/undifferentiated features (81.9%, 95% CI%: 79.7-84.2%). A positive family history of gastric cancer was the most important risk factor associated with the development of gastric carcinoma in young individuals (pooled odds ratios 4.0, 95% CI: 2.8-5.2), followed by H. pylori infection (odds ratio 2.3; 95% CI: 1.4-3.2) and dietary and other lifestyle risk factors. DISCUSSION: Young-onset gastric carcinoma exhibits specific clinicopathological characteristics, with positive family history being the most important risk factor. Most of the patients were symptomatic at diagnosis. These findings could help to inform future strategies for the early detection of gastric carcinoma among young individuals.

AttMOT: Improving Multiple-Object Tracking by Introducing Auxiliary Pedestrian Attributes.

Multiobject tracking (MOT) is a fundamental problem in computer vision with numerous applications, such as intelligent surveillance and automated driving. Despite the significant progress made in MOT, pedestrian attributes, such as gender, hairstyle, body shape, and clothing features, which contain rich and high-level information, have been less explored. To address this gap, we propose a simple, effective, and generic method to predict pedestrian attributes to support general reidentification (Re-ID) embedding. We first introduce attribute multi-object tracking (AttMOT), a large, highly enriched synthetic dataset for pedestrian tracking, containing over 80k frames and six million pedestrian identity switches (IDs) with different times, weather conditions, and scenarios. To the best of authors' knowledge, AttMOT is the first MOT dataset with semantic attributes. Subsequently, we explore different approaches to fuse Re-ID embedding and pedestrian attributes, including attention mechanisms, which we hope will stimulate the development of attribute-assisted MOT. The proposed method attribute-assisted method (AAM) demonstrates its effectiveness and generality on several representative pedestrian MOT benchmarks, including MOT17 and MOT20, through experiments on the AttMOT dataset. When applied to the state-of-the-art trackers, AAM achieves consistent improvements in multi-object tracking accuracy (MOTA), higher order tracking accuracy (HOTA), association accuracy (AssA), IDs, and IDF1 scores. For instance, on MOT17, the proposed method yields a + 1.1 MOTA, + 1.7 HOTA, and + 1.8 IDF1 improvement when used with FairMOT. To further encourage related research, we release the data and code at https://github.com/HengLan/AttMOT.

Global burden of young-onset gastric cancer: a systematic trend analysis of the global burden of disease study 2019.

BACKGROUND: While gastric cancer is generally declining globally, the temporal trend of young-onset (< 40 years) gastric cancer remains uncertain. We performed this analysis to determine the temporal trends of young-onset gastric cancer compared to late-onset cancer (≥ 40 years). METHODS: We extracted cross-sectional data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The burden of gastric cancer from 1990 to 2019 was assessed through indicators including incidence and mortality rates, which were classified at global, national, and regional levels, and according to socio-demographic indexes (SDI) and age or sex groups. Joinpoint regression analysis was used to identify specific years with significant changes. The correlation between AAPC with countries' average SDI was tested by Pearson's Test. RESULTS: The global incidence rate of young-onset gastric cancer decreased from 2.20 (per 100,000) in 1990 to 1.65 in 2019 (AAPC: - 0.95; 95% confidence interval [CI] - 1.25 to - 0.65; P < 0.001). Late-onset cancer incidence also decreased from 59.53 (per 100,000) in 1990 to 41.26 in 2019 (AAPC: - 1.23; 95% CI - 1.39 to - 1.06, P < 0.001). Despite an overall decreasing trend, the incidence rate of young-onset cancer demonstrated a significant increase from 2015 to 2019 (annual percentage change [APC]: 1.39; 95% CI 0.06 to 2.74; P = 0.041), whereas no upward trend was observed in late-onset cancer. Mortality rates of young- and late-onset cancer both exhibited a significant decline during this period (AAPC: - 1.82; 95% CI - 2.15 to - 1.56; P < 0.001 and AAPC: - 1.69, 95% CI - 1.79 to - 1.59; P < 0.001). The male-to-female rate ratio for incidence and mortality in both age groups have been increasing since 1990. While countries with high SDI have had a greater decline in the incidence of late-onset gastric cancer (slope of AAPC change: - 0.20, P = 0.004), it was not observed in young-onset cancer (slope of AAPC change: - 0.11, P = 0.13). CONCLUSIONS: The global incidence and mortality rates of both young- and late-onset gastric cancer have decreased since 1990. However, the incidence rate of young-onset cancer has demonstrated a small but significant upward trend since 2015. There was disparity in the decline in young-onset gastric cancer among male and high SDI countries. These findings could help to inform future strategies in preventing gastric cancer in younger individuals.

OXPHOS-targeted nanoparticles for boosting photodynamic therapy against hypoxia tumor.

Hypoxia as an inherent feature in tumors is firmly associated with unsatisfactory clinical outcomes of photodynamic therapy (PDT) since the lack of oxygen leads to ineffective reactive oxygen species (ROS) productivity for tumor eradication. In this study, an oxidative phosphorylation (OXPHOS) targeting nanoplatform was fabricated to alleviate hypoxia and enhance the performance of PDT by encapsulating IR780 and OXPHOS inhibitor atovaquone (ATO) in triphenylphosphine (TPP) modified poly(ethylene glycol) methyl ether-block-poly(L-lactide-co-glycolide) (mPEG-PLGA) nanocarriers (TNPs/IA). ATO by interrupting the electron transfer in OXPHOS could suppress mitochondrial respiration of tumor cells, economising on oxygen for the generation of ROS. Benefiting from the mitochondrial targeting function of TPP, ATO was directly delivered to its site of action to obtain highlighted effect at a lower dosage. Furthermore, positioning the photosensitizer IR780 to mitochondria, a more vulnerable organelle to ROS, was a promising method to attenuate the spatiotemporal limitation of ROS caused by its short half-life and narrow diffusion radius. As a result, TNPs/IA exhibited accurate subcellular localization, lead to the collapse of ATP production by damaging mitochondrion and elicited significant antitumor efficacy via oxygen-augmented PDT in the HeLa subcutaneous xenograft model. Overall, TNPs/IA was a potential strategy in photodynamic eradication of tumors.

Sarcopenia among treated cancer patients before and after neoadjuvant chemotherapy: a systematic review and meta-analysis of high-quality studies.

BACKGROUND: Neoadjuvant chemotherapy, used to shrink tumors before surgery, is increasingly applied in clinical practice. However, retrospective studies indicate that it may increase sarcopenia rates and consequently result in an elevated occurrence rate of postoperative severe complications such as severe surgical incision infection, severe respiratory failure, and severe postoperative hemorrhage, especially in the elderly population. Currently, no systematic analysis examines the association between neoadjuvant chemotherapy and sarcopenia. This study aims to fill this gap with a comprehensive meta-analysis focused on this critical aspect of the field. METHODS: A systematic literature search was conducted in the PubMed and Web of Science databases from their inception to January 2024. The included studies encompassed patients who received neoadjuvant chemotherapy and underwent computed tomography (CT) scans both before and after treatment to calculate skeletal muscle index (SMI) or categorize them for the presence of sarcopenia. The determination of sarcopenia status was based on well-established and validated threshold criteria. Data extraction was performed independently by two reviewers. A meta-analysis was employed to estimate the pooled odds ratio (OR) and its corresponding 95% confidence interval (95% CI) to assess the risk of neoadjuvant chemotherapy-induced muscle reduction. RESULTS: In the 14 studies with complete categorical variable data, comprising 1853 patients, 773 patients were identified as having sarcopenia before neoadjuvant treatment and 941 patients had sarcopenia after neoadjuvant therapy. The OR and its 95% CI was calculated as 1.51 [1.31, 1.73]. Among these, 719 patients had digestive system cancer, with 357 patients having sarcopenia before neoadjuvant treatment and 447 patients after, resulting in an OR of 1.74 [1.40, 2.17]. In the remaining 1134 patients with non-digestive system cancers, 416 were identified as having sarcopenia before neoadjuvant treatment, and 494 patients had sarcopenia after, with an OR of 1.37 [1.15, 1.63]. Additionally, in seven studies with complete continuous variable data, including 1228 patients, the mean difference in the change of SMI before and after neoadjuvant treatment was - 1.13 [- 1.65, - 0.62]. After excluding low-quality small-sample studies with fewer than 50 patients, the same trend was observed in the analysis. CONCLUSION: The risk of muscle reduction significantly increases in cancer patients after neoadjuvant chemotherapy and digestive system cancers tend to have a higher risk of developing sarcopenia post-treatment compared to non-digestive system cancers.

Iodide Vacancy Defects Clustering in Pairs Rather Than in Isolation in a Lead Iodide Perovskite: Identification, Origin, and Implications.

Iodide (I-) vacancy defects are strongly related to the stability of perovskite optoelectronic devices. The I- vacancy in lead iodide perovskites is normally considered to exist in the form of a single isolated defect. However, we determined that the I- vacancies cluster in pairs in specific ways in the typical perovskite of tetragonal CsPbI3. This I- vacancy-vacancy dimer is energetically more favorable than two isolated I- monovacancies. It breaks the symmetry of the Pb-I octahedron, resulting in lattice distortion. Its origin lies in the special lattice distortion effect caused by the electron orbital interaction of the perovskite material. Furthermore, the I- vacancy-vacancy dimer and the associated lattice distortion increase the carrier lifetime by 1.3 times compared to that of the system with two isolated I- monovacancies, but they also compromise its structural stability. This new insight into the I- vacancy defect will enhance our understanding of perovskite optoelectronic devices.

Correction: Li et al. Fabrication of Poly Dopamine@poly (Lactic Acid-Co-Glycolic Acid) Nanohybrids for Cancer Therapy via a Triple Collaboration Strategy. Nanomaterials 2023, 13, 1447.

The authors regret that, in the published article [...].

Enhanced detection of acrylamide using a versatile solid-state upconversion sensor through spectral and visual analysis.

Acrylamide (AM) generally forms in high-temperature processes and has been classified as a potential carcinogen. In this study, we put forward a maneuverable solid-state luminescence sensor using polydimethylsiloxane (PDMS) as the matrix coupled with upconversion nanoparticles as the indicator. The core-shell upconversion nanoparticles emitting cyan light were uniformly encapsulated in PDMS. Then it was further modified with complementary DNA of AM aptamer. The nanocrystalline fluorescein isothiocyanate isomer (FITC), coupled with AM aptamer, was attached to the surface of PDMS. FITC effectively quenched the upconversion luminescence through fluorescence resonance energy transfer (FRET). The introduction of AM resulted in preferentially bound to aptamer caused the separation of the quencher and the donor, and led to luminescence recovery. The developed sensor was applied for both spectral and visual monitoring, demonstrating a detection limit (LOD) of 1.00 nM and 1.07 nM, respectively. Importantly, in the actual foodstuffs detection, there is no obvious difference between the results of this study and the standard method, which indicates the developed method has good accuracy. Therefore, this solid-state sensor has the potential for on-site detection using a smartphone device and an Android application.

Prevalence and temporal trend of gastric preneoplastic lesions in Asia: A systematic review with meta-analysis.

BACKGROUND: Gastric cancer is the fifth most common cancer globally, with about 75% of cases occurring in Asia. While chronic atrophic gastritis (CAG) and intestinal metaplasia (IM) are well-recognized preneoplastic gastric lesions, we determined the prevalence and temporal trend of CAG and IM in Asia over the past 50 years. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, MEDLINE, Scopus, and Web of Science for studies reporting the prevalence of CAG and IM in Asia (according to the United Nations geoscheme) published between 1970 and 2022. Heterogeneity was assessed by the I2 index and Cochran Q test. We adopted the random effects model to estimate the pooled prevalence and 95% confidence interval (CI). The slope of prevalence was estimated as a function of time in simple linear regression and weighted meta-regression models to demonstrate the temporal trend. Studies that reported the odds ratio (OR) of Helicobacter pylori infection and CAG/IM were analyzed separately to compile a pooled OR with a 95% CI. This study was registered in INPLASY2022120028. RESULTS: Of the 81 studies from 19 Asian countries identified, the pooled prevalence for CAG and IM in Asia was 26.1% (95%CI: 22.7-30.0) and 22.9% (95%CI: 19.7-26.6), respectively. Over the past 5 decades, there was a significant decline in the prevalence of IM (slope in adjusted meta-regression models: -0.79 [95%CI: -1.28 to -0.26], P = 0.003), but there was no significant change in the pooled prevalence of CAG. Within Asia, the prevalence varied significantly among different regions. Southern Asia reported the highest pooled prevalence of CAG (42.9%, 95%CI: 27.5%-67.1%), while Western Asia reported the lowest level (12.7%, 95%CI: 5.0%-32.3%). For IM, Eastern Asia reported the highest prevalence (27.1%, 95%CI: 21.1-34.9), with the lowest prevalence reported in Western Asia (3.1%; 95% CI 1.2%-8.0%). H. pylori infection was linked to CAG and IM with OR of 2.16 (95%CI: 2.09-2.22) and 1.64 (95%CI: 1.57-1.72), respectively. CONCLUSION: This updated meta-analysis showed that up to 26% of study individuals in Asia harbored preneoplastic gastric lesions. There was a declining temporal trend in the prevalence of IM, but not for CAG, in Asia.

Slim UNETR: Scale Hybrid Transformers to Efficient 3D Medical Image Segmentation Under Limited Computational Resources.

Hybrid transformer-based segmentation approaches have shown great promise in medical image analysis. However, they typically require considerable computational power and resources during both training and inference stages, posing a challenge for resource-limited medical applications common in the field. To address this issue, we present an innovative framework called Slim UNETR, designed to achieve a balance between accuracy and efficiency by leveraging the advantages of both convolutional neural networks and transformers. Our method features the Slim UNETR Block as a core component, which effectively enables information exchange through self-attention mechanism decomposition and cost-effective representation aggregation. Additionally, we utilize the throughput metric as an efficiency indicator to provide feedback on model resource consumption. Our experiments demonstrate that Slim UNETR outperforms state-of-the-art models in terms of accuracy, model size, and efficiency when deployed on resource-constrained devices. Remarkably, Slim UNETR achieves 92.44% dice accuracy on BraTS2021 while being 34.6x smaller and 13.4x faster during inference compared to Swin UNETR. Code: https://github.com/aigzhusmart/Slim-UNETR.

Cause of death during nasopharyngeal carcinoma survivorship: a population-based analysis.

Background: Recently, the survival rate of nasopharyngeal carcinoma (NPC) patients has improved greatly due to developments in NPC treatments. But cause-specific mortality in NPC patients remains unclear. This study aims to investigate the common causes of death in NPC patients. Methods: Eligible patients with NPC were included from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized mortality ratios(SMRs) were calculated to compare death rates in NPC patients with those in the general population. Results: A total of 3475 patients with NPC were included, of whom 1696 patients died during the follow-up period. 52.83% of deaths were caused by NPC, followed by other cancers (28.13%) and non-cancer causes (18.46%). The proportion of patients who died of NPC decreased over survival time. Moreover, non-cancer causes of death increase from 12.94% to 51.22% over time after 10 years of diagnosis. Heart diseases was the most common non-cancer cause of death in NPC patients. Conclusions: Although NPC remains the leading cause of death after NPC diagnosis, other non-NPC causes of death represent an increased number of death in NPC patients. These findings support the involvement of multidisciplinary care for follow-up strategy in NPC patients.

Near-Infrared Photothermal Manipulates Cellular Excitability and Animal Behavior in Caenorhabditis elegans.

Near-infrared (NIR) photothermal manipulation has emerged as a promising and noninvasive technology for neuroscience research and disease therapy for its deep tissue penetration. NIR stimulated techniques have been used to modulate neural activity. However, due to the lack of suitable in vivo control systems, most studies are limited to the cellular level. Here, a NIR photothermal technique is developed to modulate cellular excitability and animal behaviors in Caenorhabditis elegans in vivo via the thermosensitive transient receptor potential vanilloid 1 (TRPV1) channel with an FDA-approved photothermal agent indocyanine green (ICG). Upon NIR stimuli, exogenous expression of TRPV1 in AFD sensory neurons causes Ca2+ influx, leading to increased neural excitability and reversal behaviors, in the presence of ICG. The GABAergic D-class motor neurons can also be activated by NIR irradiation, resulting in slower thrashing behaviors. Moreover, the photothermal manipulation is successfully applied in different types of muscle cells (striated muscles and nonstriated muscles), enhancing muscular excitability, causing muscle contractions and behavior changes in vivo. Altogether, this study demonstrates a noninvasive method to precisely regulate the excitability of different types of cells and related behaviors in vivo by NIR photothermal manipulation, which may be applied in mammals and clinical therapy.

TRPM2 as a conserved gatekeeper determines the vulnerability of DA neurons by mediating ROS sensing and calcium dyshomeostasis.

Different dopaminergic (DA) neuronal subgroups exhibit distinct vulnerability to stress, while the underlying mechanisms are elusive. Here we report that the transient receptor potential melastatin 2 (TRPM2) channel is preferentially expressed in vulnerable DA neuronal subgroups, which correlates positively with aging in Parkinson's Disease (PD) patients. Overexpression of human TRPM2 in the DA neurons of C. elegans resulted in selective death of ADE but not CEP neurons in aged worms. Mechanistically, TRPM2 activation mediates FZO-1/CED-9-dependent mitochondrial hyperfusion and mitochondrial permeability transition (MPT), leading to ADE death. In mice, TRPM2 knockout reduced vulnerable substantia nigra pars compacta (SNc) DA neuronal death induced by stress. Moreover, the TRPM2-mediated vulnerable DA neuronal death pathway is conserved from C. elegans to toxin-treated mice model and PD patient iPSC-derived DA neurons. The vulnerable SNc DA neuronal loss is the major symptom and cause of PD, and therefore the TRPM2-mediated pathway serves as a promising therapeutic target against PD.

Ion Solvation Cage Structure in Polymer Electrolytes Determined by Combining X-ray Scattering and Simulations.

Solvation structure plays a crucial role in determining ion transport in electrolytes. We combine wide-angle X-ray scattering (WAXS) and molecular dynamics (MD) simulation to identify the solvation cage structure in two polymer electrolytes, poly(pentyl malonate) (PPM) and poly(ethylene oxide) (PEO) mixed with lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) salt. As the salt concentration increases, the amorphous halo in the pure polymers is augmented by an additional peak at low scattering angles. The location of this peak and its height are, however, different in the two electrolytes. By decoupling the total intensity into species contributions and mapping scattering peaks to position-space molecular correlations, we elucidate distinct origins of the additional peak. In PPM, it arises from long-range charge-ordering between solvation cages and anions, while in PEO it is dominated by correlations between anions surrounding the same cage. TFSI- ions are present in the PPM solvation cage, but expelled from the PEO solvation cage.

Fabrication of Poly Dopamine@poly (Lactic Acid-Co-Glycolic Acid) Nanohybrids for Cancer Therapy via a Triple Collaboration Strategy.

Breast cancer is a common malignant tumor among women and has a higher risk of early recurrence, distant metastasis, and poor prognosis. Systemic chemotherapy is still the most widely used treatment for patients with breast cancer. However, unavoidable side effects and acquired resistance severely limit the efficacy of treatment. The multi-drug combination strategy has been identified as an effective tumor therapy pattern. In this investigation, we demonstrated a triple collaboration strategy of incorporating the chemotherapeutic drug doxorubicin (DOX) and anti-angiogenesis agent combretastatin A4 (CA4) into poly(lactic-co-glycolic acid) (PLGA)-based co-delivery nanohybrids (PLGA/DC NPs) via an improved double emulsion technology, and then a polydopamine (PDA) was modified on the PLGA/DC NPs' surface through the self-assembly method for photothermal therapy. In the drug-loaded PDA co-delivery nanohybrids (PDA@PLGA/DC NPs), DOX and CA4 synergistically induced tumor cell apoptosis by interfering with DNA replication and inhibiting tumor angiogenesis, respectively. The controlled release of DOX and CA4-loaded PDA@PLGA NPs in the tumor region was pH dependent and triggered by the hyperthermia generated via laser irradiation. Both in vitro and in vivo studies demonstrated that PDA@PLGA/DC NPs enhanced cytotoxicity under laser irradiation, and combined therapeutic effects were obtained when DOX, CA4, and PDA were integrated into a single nanoplatform. Taken together, the present study demonstrates a nanoplatform for combined DOX, CA4, and photothermal therapy, providing a potentially promising strategy for the synergistic treatment of breast cancer.