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Abstract Low-grade heat is abundant and ubiquitous, but it is generally discarded due to the lack of cost-effective recovery technologies. Ion thermoelectric cells are an affordable and straightforward approach of converting low-grade heat into usable electricity for sustainable power. Despite their potential, ion thermoelectric cells face challenges such as limited Seebeck coefficient and required series integration. Here, we demonstrate that the N-type and P-type conversion of ion thermoelectric cells can be achieved through the phase transition of temperature-sensitive hydrogel containing the triiodide/iodide redox couple. Through the strong interaction between the hydrophobic region of the hydrogel and triiodide, the hydrophobic side selectively captures triiodide and the hydrophilic side repels triiodide, raising the concentration difference of triiodide and thereby increasing the Seebeck coefficient. Specifically, the Seebeck coefficient of the N-type ion thermoelectric cells is 7.7 mV K−1, and the Seebeck coefficient of P-type ion thermoelectric cells is −6.3 mV K−1 (ΔT = 15 K). By connecting 10 pairs of the N-type and P-type ion thermoelectric cells, we achieve a voltage of 1.8 V and an output power of 85 μW, surpassing the reported triiodide/iodide-based ion thermoelectric cells. Our work proposes a phase transition strategy for the N-P conversion of ion thermoelectric cells, and highlights the prospect of series integrated hydrogel ion thermoelectric cells for low-grade heat harvesting.

Abstract Background Rapidly expanding human activities have profoundly changed the habitat use of both large carnivores and their prey, but whether and how human activities affect the interactions between them has received relatively less attention. In this study, we conducted a systematically designed camera-trapping survey on an endangered large carnivore (North Chinese leopard Panthera pardus japonensis) and its wild ungulate prey (Siberian roe deer Capreolus pygargus and wild boar Sus scrofa) in the Taihang Mountains of central North China. Using conditional two-species occupancy model based on data derived from the extensive sampling effort (15,654 camera-days at 102 camera sites), we examined the relationship of spatial use between leopards and each prey species under the effects of human presence, free-ranging cattle, roads and settlements. Results Humans and cattle had contrasting effects on the relationship of spatial use between leopard and roe deer, with higher and lower spatial segregation between them at human and cattle-frequented sites, respectively. Roads might create a shelter for wild boar from leopard predation, with less spatial segregation between them at sites close to the roads. Conclusions Our findings demonstrate that human activities are reshaping the spatial overlap between large carnivores and their prey, and have non-equivalent effects among different types of human activity. Such effects may further alter the strength of interspecific interactions between predator and prey, with far-reaching influences on the community and ecosystem that require more research.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Synergistic effects of herbicidal rice husks and pyrolysis liquid from waste wood-based panels were studied relative to the germination of three common weed species in a tea plantation. The pyrolysis liquid consisted of various organic acids, phenols, alcohols, ketones, and nitrogen compounds, with organic acids accounting for up to 46.8% of the content. Three seeds of smooth crabgrass (Digitaria ischaemum), annual fleabane (Erigeron annuus), and hedge-parsley (Torilis scabra (Thunb.) DC) were treated with 2000 and 4000 L/ha of pyrolysis liquid, as well as 50, 100, and 200 m3/ha of pyrolysis liquid as a cover material. The pre-emergence herbicide tests demonstrated that the combination of rice husks and pyrolysis liquid effectively inhibited seed germination and aboveground biomass of the weeds. The weed control effect increased with the increase in the amount applied. The combination of rice husks (200 m3/ha) and pyrolysis liquid (4000 L/ha) exhibited the highest weed control efficacy, reducing seed germination and aboveground biomass by 69.1%, 79.5%, and 97.6% for smooth crabgrass, annual fleabane, and hedge-parsley, respectively. Discarded furniture materials and rice husks can both be used as sustainable materials for weed control, offering a fresh approach to the efficient utilization of waste materials.

Abstract Background Even with advances in primary health care, depressive disorders remain a major global public health problem. We conducted an in-depth analysis of global, regional and national trends in depressive disorders incidence over the past 30 years. Methods Data on the incidence of depressive disorders were obtained by sex (female, male, and both), location (204 countries), age (5–84 years), year (1990–2019) from the Global Burden of Disease Study (GBD) 2019. Further, age-period-cohort modeling was used to estimate the net drift, local drift, age, period and cohort effects between 1990 and 2019. Results In 2019, although the incidence of depressive disorders has increased by 59.3% to 290 million (95% UI: 256, 328), the age-standardized incidence rate has decreased by 2.35% to 3588.25 per 100,000 people (3152.71, 4060.42) compared to 1990. There was an emerging transition of incidences from the young and middle-aged population to the old population. From 1990 to 2019, the net drift of incidence rate ranged from −0.54% (−0.61%, −0.47%) in low-middle Socio-demographic Index (SDI) regions to 0.52% (0.25%, 0.79%) in high SDI regions. Globally, the incidence rate of depressive disorders increases with age, period effects showing a decreasing risk and cohort effects beginning to decline after the 1960s. Conclusions Our current findings reflect substantial health disparities and potential priority-setting of depressive disorders incidence in the three dimensions of age, period and cohort across SDI regions, countries. The scope of healthcare to improve the progression of depressive disorders events can be expanded to include males, females of all ages.

Shell-tube PCM energy storage units are used in cold storage devices, the heat removal process is a critical factor influencing their performance. This study investigates the effects of cooling water temperature, water velocity, and tube shape on the heat removal process of shell-tube PCM energy storage units through both experiments and numerical simulations. The energy performance was analyzed based on the energy consumption of the chiller and water pump. The results show that the spiral tube has the highest heat removal rate and the greatest resistance loss, but also the lowest chiller energy consumption. Additionally, the study found that for every 1 °C increase in cooling water temperature, the heat removal time increases by approximately 13.9 %, the energy efficiency ratio (EER) decreases by about 9.5 %, and the chiller energy consumption decreases by about 5 %. Higher cooling water velocity can improve the heat removal rate but reduces the EER. Beyond tube shape, both the cooling water temperature and velocity affect the PCM liquid fraction distribution inside the shell, thereby influencing the energy consumption during the sensible heat removal of solid-state PCM. The EER of the sensible heat removal process for solid-state PCM is lower compared to that of liquid and hybrid states.

Abstract The burgeoning demand for healthcare monitoring has brought field effect transistor (FET) biosensors into the spotlight as a highly efficient detection technology. FET biosensors offer inherent advantages including high sensitivity, rapid response times, operational simplicity, integrability, and label‐free detection. These characteristics render them particularly well‐suited for detecting a diverse array of physiological parameters and biomarkers, thereby furnishing real‐time data crucial for personalized medicine and disease prevention. This review aims to elucidate recent advancements in FET biosensors within the realm of healthcare management encompassing several facets. Initially, this review systematically analyzes the device architecture, sensing mechanisms, and performance evaluation methods of FET biosensors to gain an in‐depth understanding of their operational principles and features. Subsequently, it focuses on the application of FET biosensors for detecting health‐related biomarkers encompassing nucleic acids, proteins, exosomes, viruses, etc. Lastly, the review presents engineered medical sensor prototypes predicated on FET biosensors, such as point‐of‐care testing devices, wearable sensors, and implantable sensors, underscoring their practical utility and potential in health management. In addition, the review addresses critical issues and prospects of using FET biosensors in healthcare monitoring, aiming to provide some references and insights for research and innovation in this field.

Abstract Liquid manipulation using tubular actuators finds diverse applications ranging from microfluidics, printing, liquid transfer to micro‐reactors. Achieving flexible and simple regulation of manipulated liquid droplets during transport is crucial for the tubular liquid actuators to perform complex and multiple functions, yet it remains challenging. Here, a facile tubular actuator for directional transport of various liquid droplets under the control of an externally applied magnetic field is presented. The surfaces of the actuator can be engineered with submillimeter‐sized through‐hole pores, which enables the liquid droplet to be easily modulated in the transport process. Furthermore, the liquid actuator with featured through‐hole pores is expanded to function as a switch in an integrated external electric circuit by magnetically controlling the motion of a conductive liquid droplet. This work develops a strategy for regulating liquid droplets in the tubular actuation systems, which may inspire ideas for designing functional liquid actuators with potential applications in microfluidics, microchemical reaction, liquid switch, and liquid robotics.

Abstract In this paper, Voronoi cell finite element method (VCFEM) based on assumed flux hybrid formulation has been presented for heat conduction problem of particle reinforced composites material. The heat fluxes satisfying a priori internal thermal balance are directly approximated independently in the matrix and the inclusion respectively. The temperatures on element boundary and matrix-inclusion interface are interpolated by nodal temperature. The thermal balance on the interelement boundary and matrix-inclusion interface is relaxed and introduced into the functional by taking the temperature as Lagrange multiplier. In this way, a functional containing two variables of heat flux and temperature is proposed. Full field heat flux and effective thermal conductivity are obtained. Feasibility and effectiveness of the proposed approach are verified through several numerical examples.

Cancer, a complex and heterogeneous disease, arises from genomic instability. Currently, DNA damage-based cancer treatments, including radiotherapy and chemotherapy, are employed in clinical practice. However, the efficacy and safety of these therapies are constrained by various factors, limiting their ability to meet current clinical demands. Metal nanoparticles present promising avenues for enhancing each critical aspect of DNA damage-based cancer therapy. Their customizable physicochemical properties enable the development of targeted and personalized treatment platforms. In this review, we delve into the design principles and optimization strategies of metal nanoparticles. We shed light on the limitations of DNA damage-based therapy while highlighting the diverse strategies made possible by metal nanoparticles. These encompass targeted drug delivery, inhibition of DNA repair mechanisms, induction of cell death, and the cascading immune response. Moreover, we explore the pivotal role of physicochemical factors such as nanoparticle size, stimuli-responsiveness, and surface modification in shaping metal nanoparticle platforms. Finally, we present insights into the challenges and future directions of metal nanoparticles in advancing DNA damage-based cancer therapy, paving the way for novel treatment paradigms.

Cell-free fetal DNA (cffDNA) screening is a valuable tool in clinical practice for detecting chromosomal abnormalities and autosomal dominant (AD) conditions. This study introduces a novel proof-of-concept assay designed for autosomal recessive (AR) cffDNA screening, focusing on cases involving the NPC1 gene. We aim to illustrate the significant benefits of AR cffDNA screening in managing high-risk pregnancies, specifically where biallelic pathogenic variants in NPC1 cause Niemann–Pick disease, type C1 (NPC), a disorder marked by progressive neurodegeneration. Three participants for this study were recruited and gave consent to a hospital in Saudi Arabia. These participants were either carriers of NPC or had a first- or second-degree relative affected by the disorder. No specific criteria were set for the age of the participants. All were between 15 and 18 weeks of gestation. Using amplicon-based next-generation sequencing (NGS), we analyzed the zygosity and variants in cffDNA extracted from maternal peripheral blood. After amplicon NGS, analysis was completed by a custom data analysis pipeline that included in-house-built data processing scripts and commonly used software packages. Importantly, the results were not disclosed to the patients. Our findings showed that in all three cases, AR cffDNA screening results were consistent with standard invasive diagnostic testing. This screening method offers several advantages: it provides critical information to families earlier in the pregnancy compared to invasive diagnostic tests, and it helps to alleviate parental anxiety. Moreover, this non-invasive method can determine pregnancy status in the first trimester for known familial variants. Future research may extend this approach to screen for known disease-causing variants in common AR conditions.

Abstract Background Undetermined lung nodules are common in locally advanced rectal cancer (LARC) and lack precise risk stratification. This study aimed to develop a radiomic‐based score (Rad‐score) to distinguish metastasis and predict overall survival (OS) in patients with LARC and lung nodules. Methods Retrospective data from two institutions (July 10, 2006—September 24, 2015) was used to develop and validate the Rad‐score for distinguishing lung nodule malignancy. The prognostic value of the Rad‐score was investigated in LARC cohorts, leading to the construction and validation of a clinical and radiomic score (Cli‐Rad‐score) that incorporates both clinical and radiomic information for the purpose of improving personalized clinical prognosis prediction. Descriptive statistics, survival analysis, and model comparison were performed to assess the results. Results The Rad‐score demonstrated great performance in distinguishing malignancy, with C‐index values of 0.793 [95% CI: 0.729–0.856] in the training set and 0.730 [95% CI: 0.666–0.874] in the validation set. In independent LARC cohorts, Rad‐score validation achieved C‐index values of 0.794 [95% CI: 0.737–0.851] and 0.747 [95% CI: 0.615–0.879]. Regarding prognostic prediction, Rad‐score effectively stratified patients. Cli‐Rad‐score outperformed the clinicopathological information alone in risk stratification, as evidenced by significantly higher C‐index values (0.735 vs. 0.695 in the internal set and 0.618 vs. 0.595 in the external set). Conclusions CT‐based radiomics could serve as a reliable and powerful tool for lung nodule malignancy distinction and prognostic prediction in LARC patients. Rad‐score predicts prognosis independently. Incorporation of Cli‐Rad‐score significantly enhances the persionalized clinical prognostic capacity in LARC patients with lung nodules.

Abstract Precise agriculture based on intelligent agriculture plays a significant role in sustainable development. The agricultural Internet of Things (IoTs) is a crucial foundation for intelligent agriculture. However, the development of agricultural IoTs has led to exponential growth in various sensors, posing a major challenge in achieving long‐term stable power supply for these distributed sensors. Introducing a self‐powered active biochemical sensor can help, but current sensors have poor sensitivity and specificity making this application challenging. To overcome this limitation, a triboelectric nanogenerator (TENG)‐based self‐powered active urea sensor which demonstrates high sensitivity and specificity is developed. This device achieves signal enhancement by introducing a volume effect to enhance the utilization of charges through a novel dual‐electrode structure, and improves the specificity of urea detection by utilizing an enzyme‐catalyzed reaction. The device is successfully used to monitor the variation of urea concentration during crop growth with concentrations as low as 4 µm, without being significantly affected by common fertilizers such as potassium chloride or ammonium dihydrogen phosphate. This is the first self‐powered active biochemical sensor capable of highly specific and highly sensitive fertilizer detection, pointing toward a new direction for developing self‐powered active biochemical sensor systems within sustainable development‐oriented agricultural IoTs.

Weather radar holds the capability to monitor the extensive migration of bird and insect species. In particular, polarimetric weather radar can enhance aerial ecological monitoring by quantifying target shape through the measurement of polarization moments. This article introduces an intelligent algorithm to classify bird and insect migration using polarimetric weather radar data. A radar image dataset was formed by intentionally curating typical migratory data of birds and insects captured by the polarimetric weather radar. Next, point features and spatial texture features were extracted from the radar images in the dataset for training a classifier using a supervised learning approach, resulting in a classification accuracy of 93.56%. Furthermore, the importance of the features was analyzed, uncovering that the most influential attribute was the reflectivity factor at 33.83%, surpassing the cumulative influence of other dual-polarization moments. In addition, spatial textures also played an essential role for the classifier, collectively weighing 35.65%. Lastly, the proposed method was validated with bird radar data, attaining an accuracy level of 95.36%.

The fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

Abstract Background Endoplasmic reticulum (ER) stress, promoting lipid metabolism disorders and steatohepatitis, contributes significantly to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Hugan Qingzhi tablets (HQT) has a definite effect in the clinical treatment of NAFLD patients, but its mechanism is still unclear. This study aims to investigate the effects of HQT on ER stress in the liver tissues of NAFLD rats and explore the underlying mechanism. Methods The NAFLD rat model was managed with high-fat diet (HFD) for 12weeks. HQT was administrated in a daily basis to the HFD groups. Biochemical markers, pro-inflammatory cytokines, liver histology were assayed to evaluate HQT effects in HFD-induced NAFLD rats. Furthermore, the expression of ER stress-related signal molecules including glucose regulating protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), p-PERK, eukaryotic translation initiation factor 2α (EIF2α), p-EIF2α, activating transcription factor 4 (ATF4), acetyl-coenzyme A-carboxylase (ACC), activating transcription factor (ATF6), and nuclear factor-kappa B-p65 (NF-κB-p65) were detected by western blot and/or qRT-PCR. Results The histopathological characteristics and biochemical data indicated that HQT exhibited protective effects on HFD-induced NAFLD rats. Furthermore, it caused significant reduction in the expression of ERS markers, such as GRP78, PERK, p-PERK, and ATF6, and subsequently downregulated the expression of EIF2α, p-EIF2α ATF4, ACC, and NF-κB-p65. Conclusions The results suggested that HQT has protective effect against hepatic steatosis and inflammation in NAFLD rats by attenuating ER stress, and the potential mechanism is through inhibition of PERK and ATF6 pathways.

Abstract Background Circular RNAs (circRNAs) play a significant role in the tumorigenesis and progression of diverse human cancers, including lung adenocarcinoma. A previous study suggested that circ_0004140 expression was increased in lung adenocarcinoma cells. However, the molecular mechanism of circRNA circ_0004140 involved in lung adenocarcinoma is poorly defined. Methods Circ_0004140, microRNA‐330‐5p (miR‐330‐5p), and NOVA alternative splicing regulator 2 (NOVA2) expression were determined by real‐time quantitative polymerase chain reaction (RT‐qPCR). Cell proliferation, apoptosis, migration, invasion, and angiogenesis ability were assessed using 5‐ethynyl‐2’‐deoxyuridine (EdU), flow cytometry, wound healing, transwell, and capillary‐like network formation assays. Proliferating cell nuclear antigen (PCNA), cyclin D1, and NOVA2 protein levels were detected using Western blot assay. The interaction between miR‐330‐5p and circ_0004140 or NOVA2 was verified by dual‐luciferase reporter assay. Xenograft tumor model was utilized to assess the role of circ_0004140 in tumor growth in vivo. Results Circ_0004140 was upregulated in lung adenocarcinoma tissues and cell lines. Circ_0004140 silencing suppressed cell proliferation, migration, invasion and tube formation ability, and triggered the apoptosis of lung adenocarcinoma cells. Circ_0004140 acted as a molecular sponge for miR‐330‐5p, and miR‐330‐5p silencing largely reversed circ_0004140 knockdown‐induced effects in lung adenocarcinoma cells. NOVA2 was a target of miR‐330‐5p, and NOVA2 overexpression might largely overturn miR‐330‐5p overexpression‐induced influences in lung adenocarcinoma cells. Circ_0004140 upregulated NOVA2 expression via sponging miR‐330‐5p in lung adenocarcinoma cells. Circ_0004140 silencing restrained xenograft tumor growth in vivo. Conclusion Circ_0004140 knockdown might suppress the malignant biological behaviors of lung adenocarcinoma cells via miR‐330‐5p‐dependent regulation of NOVA2.

Abstract G protein-coupled receptors (GPCRs) are versatile and vital proteins involved in a wide array of physiological processes and responses, such as sensory perception (e.g., vision, taste, and smell), immune response, hormone regulation, and neurotransmission. Their diverse and essential roles in the body make them a significant focus for pharmaceutical research and drug development. Currently, approximately 35% of marketed drugs directly target GPCRs, underscoring their prominence as therapeutic targets. Recent advances in structural biology have substantially deepened our understanding of GPCR activation mechanisms and interactions with G-protein and arrestin signaling pathways. This review offers an in-depth exploration of both traditional and recent methods in GPCR structure analysis. It presents structure-based insights into ligand recognition and receptor activation mechanisms and delves deeper into the mechanisms of canonical and noncanonical signaling pathways downstream of GPCRs. Furthermore, it highlights recent advancements in GPCR-related drug discovery and development. Particular emphasis is placed on GPCR selective drugs, allosteric and biased signaling, polyphamarcology, and antibody drugs. Our goal is to provide researchers with a thorough and updated understanding of GPCR structure determination, signaling pathway investigation, and drug development. This foundation aims to propel forward-thinking therapeutic approaches that target GPCRs, drawing upon the latest insights into GPCR ligand selectivity, activation, and biased signaling mechanisms.

Corona Virus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has presented unprecedented challenges to the world. Changes after acute COVID-19 have had a significant impact on patients with neurodegenerative diseases. This study aims to explore the mechanism of neurodegenerative diseases by examining the main pathways of central nervous system infection of SARS-CoV-2. Research has indicated that chronic inflammation and abnormal immune response are the primary factors leading to neuronal damage and long-term consequences of COVID-19. In some COVID-19 patients, the concurrent inflammatory response leads to increased release of pro-inflammatory cytokines, which may significantly impact the prognosis. Molecular imaging can accurately assess the severity of neurodegenerative diseases in patients with COVID-19 after the acute phase. Furthermore, the use of FDG-PET is advocated to quantify the relationship between neuroinflammation and psychiatric and cognitive symptoms in patients who have recovered from COVID-19. Future development should focus on aggressive post-infection control of inflammation and the development of targeted therapies that target ACE2 receptors, ERK1/2, and Ca2+.

【Objective】 To clarify the water requirement law of sunflower and improve the coupling effect of water and nitrogen. 【Method】 A plot experiment was conducted to set three irrigation amounts, namely, rain-fed W0, supplementary W1 67.5 mm and conventional irrigation W2 135 mm, and three nitrogen application levels, namely, N0 (no nitrogen application), recommended nitrogen N1 135 kg/hm2 and excess nitrogen N2 270 kg/hm2, respectively. The effects of water and nitrogen coupling on yield, water consumption, water use efficiency, fertilizer utilization rate and water and nitrogen coupling effect of sunflower were studied. 【Result】 A plot experiment was conducted to set three irrigation amounts, namely, rain-fed W0, supplementary W1 67.5 mm and conventional irrigation W2 135 mm, and three nitrogen application levels, namely, N0 (no nitrogen application), recommended nitrogen N1 135 kg/hm2 and excess nitrogen N2 270 kg/hm2, respectively. The effects of water and nitrogen coupling on yield, water consumption, water use efficiency, fertilizer utilization rate and water and nitrogen coupling effect of sunflower were studied. 【Conclusion】 The suitable fertilization and irrigation mode for Sunflowers at the North Foot of Yinshan Mountain is the supplementary irrigation amount of 159.2~177.1 mm and the nitrogen rates of 166~218.3 kg/hm2. The 12-leaf - opening stage is the key period of water and fertilizer demand, and the supply of water and fertilizer should be ensured.

Abstract The PI3K/AKT pathway plays an essential role in tumour development. NOD-like receptors (NLRs) regulate innate immunity and are implicated in cancer, but whether they are involved in PI3K/AKT pathway regulation is poorly understood. Here, we report that NLRP6 potentiates the PI3K/AKT pathway by binding and destabilizing p85α, the regulatory subunit of PI3K. Mechanistically, NLRP6 recruits the E3 ligase RBX1 to p85α and ubiquitinates lysine 256 on p85α, which is recognized by the autophagy cargo receptor OPTN, causing selective autophagic degradation of p85α and subsequent activation of the PI3K/AKT pathway by reducing PTEN stability. We further show that loss of NLRP6 suppresses cell proliferation, colony formation, cell migration, and tumour growth in glioblastoma cells in vitro and in vivo. Disruption of the NLRP6/p85α interaction using the Pep9 peptide inhibits the PI3K/AKT pathway and generates potent antitumour effects. Collectively, our results suggest that NLRP6 promotes p85α degradation via selective autophagy to drive tumorigenesis, and the interaction between NLRP6 and p85α can be a promising therapeutic target for tumour treatment.

Ni-rich Li(NixCoyMnz)O2 (x ≥ 0.8)-layered oxide materials are highly promising as cathode materials for high-energy-density lithium-ion batteries in electric and hybrid vehicles. However, their tendency to undergo side reactions with electrolytes and their structural instability during cyclic lithiation/delithiation impairs their electrochemical cycling performance, posing challenges for large-scale applications. This paper explores the application of an Al2O3 coating using an atomic layer deposition (ALD) system on Ni-enriched Li(Ni0.8Co0.1Mn0.1)O2 (NCM811) cathode material. Characterization techniques, including X-ray diffraction, scanning electron microscopy, and transmission electron microscopy, were used to assess the impact of alumina coating on the morphology and crystal structure of NCM811. The results confirmed that an ultrathin Al2O3 coating was achieved without altering the microstructure and lattice structure of NCM811. The alumina-coated NCM811 exhibited improved cycling stability and capacity retention in the voltage range of 2.8–4.5 V at a 1 C rate. Specifically, the capacity retention of the modified NCM811 was 5%, 9.11%, and 11.28% higher than the pristine material at operating voltages of 4.3, 4.4, and 4.5 V, respectively. This enhanced performance is attributed to reduced electrode–electrolyte interaction, leading to fewer side reactions and improved structural stability. Thus, NCM811@Al2O3 with this coating process emerges as a highly attractive candidate for high-capacity lithium-ion battery cathode materials.

The in vitro maturation efficiency of porcine oocytes is relatively low, and this limits the production of in vitro porcine embryos. Since melatonin is involved in mammalian reproductive physiology, in this study, we have explored whether endogenously produced melatonin can help in porcine oocyte in vitro maturation. We have found, for the first time in the literature, that mitochondria are the major sites for melatonin biosynthesis in porcine oocytes. This mitochondrially originated melatonin reduces ROS production and increases the activity of the mitochondrial respiratory electron transport chain, mitochondrial biogenesis, mitochondrial membrane potential, and ATP production. Therefore, melatonin improves the quality of oocytes and their in vitro maturation. In contrast, the reduced melatonin level caused by siRNA to knockdown AANAT (siAANAT) is associated with the abnormal distribution of mitochondria, decreasing the ATP level of porcine oocytes and inhibiting their in vitro maturation. These abnormalities can be rescued by melatonin supplementation. In addition, we found that siAANAT switches the mitochondrial oxidative phosphorylation to glycolysis, a Warburg effect. This metabolic alteration can also be corrected by melatonin supplementation. All these activities of melatonin appear to be mediated by its membrane receptors since the non-selective melatonin receptor antagonist Luzindole can blunt the effects of melatonin. Taken together, the mitochondria of porcine oocytes can synthesize melatonin and improve the quality of oocyte maturation. These results provide an insight from a novel aspect to study oocyte maturation under in vitro conditions.

Abstract Background The majority of epidemiological studies on migraine have been conducted in a specific country or region, and there is a lack of globally comparable data. We aim to report the latest information on global migraine incidence overview trends from 1990 to 2019. Methods In this study, the available data were obtained from the Global Burden of Disease 2019. We present temporal trends in migraine for the world and its 204 countries and territories over the past 30 years. Meanwhile, an age-period-cohort model be used to estimate net drifts (overall annual percentage change), local drifts (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks. Results In 2019, the global incidence of migraine increased to 87.6 million (95% UI: 76.6, 98.7), with an increase of 40.1% compared to 1990. India, China, United States of America, and Indonesia had the highest number of incidences, accounting for 43.6% of incidences globally. Females experienced a higher incidence than males, the highest incidence rate was observed in the 10–14 age group. However, there was a gradual transition in the age distribution of incidence from teenagers to middle-aged populations. The net drift of incidence rate ranged from 3.45% (95% CI: 2.38, 4.54) in high-middle Socio-demographic Index (SDI) regions to -4.02% (95% CI: -4.79, -3.18) in low SDI regions, 9 of 204 countries showed increasing trends (net drifts and its 95% CI were > 0) in incidence rate. The age-period-cohort analysis results showed that the relative risk of incidence rate generally showed unfavorable trends over time and in successively birth cohorts among high-, high-middle-, and middle SDI regions, but low-middle- and low-SDI regions keep stable. Conclusions Migraine is still an important contributor to the global burden of neurological disorders worldwide. Temporal trends in migraine incidence are not commensurate with socioeconomic development and vary widely across countries. Both sexes and all age groups should get healthcare to address the growing migraine population, especially adolescents and females.

NAC transcription factors (TFs) are one of the largest plant-specific gene families and play important roles in plant growth, development, and the biotic and abiotic stress response. Although the sequencing of Jojoba (Simmondsia chinensis) has been completed, the genome-wide identification and analysis of its NAC TFs has not been reported. In this study, a total of 57 genes were identified in Jojoba, which were divided into eight groups based on phylogenetic analysis. The genes clustered in the same groups have a similar gene structure and motif distribution. Based on the analysis of cis-elements in NAC TFs, nine cis-acting elements were identified in the promoter region that involved in light response, hormonal response, and stress response. Synteny analysis showed a greater collinearity between Jojoba and V. vinifera than Arabidopsis thaliana. The 24 genes in the Jojoba NAC TFs are derived from fragment replication, which may be the main source of NAC amplification. Gene expression analysis identified seven genes that were highly expressed in seeds. The differential expression analysis of NAC TFs in cotyledon and embryonic axis tissues showed that the expression of 10 genes was up-regulated and 1 gene was down-regulated. This study provides more information on the classification, gene structure, conserved motif, and evolution of NAC TFs in Jojoba, facilitating further exploration of their specific functional analysis in Jojoba seed development.

Introduction The preliminary result of the TORCH trial has shown a promising complete response (CR) for managing locally advanced rectal cancer with neoadjuvant short-course radiotherapy (SCRT) combined with chemotherapy and PD-1 inhibitor. For locally advanced colon cancer (LACC) with bulky nodal disease and/or clinically T4, neoadjuvant chemotherapy followed by colectomy with en bloc removal of regional lymph nodes is the suggested treatment. However, the CR rate is less than 5%. TORCH-C will aim to investigate neoadjuvant SCRT combined with chemotherapy and PD-1 inhibitor in LACC.Methods and analysis TORCH-C is a randomised, prospective, multicentre, double-arm, open, phase II trial of SCRT combined with chemotherapy and immunotherapy in LACC with microsatellite stable (MSS) patients and cT4 or bulky nodes. Eligible patients will be identified by the multidisciplinary team. 120 patients will be randomised 1:1 to the intervention or control arm. The patients in the control arm will receive four cycles of capecitabine plus oxaliplatin (CAPOX). The patients in the intervention arm will receive SCRT, followed by four cycles of CAPOX and PD-1 inhibitor (serplulimab). Both arms will receive curative surgery, followed by four cycles of CAPOX. The primary endpoint is pathological complete regression.TORCH-C (TORCH-colon) trial aims to investigate whether the combination of immunotherapy and chemoradiotherapy improves the treatment effect in LACC with MSS. TORCH-C will establish the TORCH platform, a key part of our long-term strategy to develop neoadjuvant treatment for colorectal cancer.Ethics and dissemination This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (approval number: 2211265-12).Trial registration number NCT05732493

Abstract In addressing the demand for hierarchically mesoporous metal‐organic frameworks (HMMOFs) with adjustable large mesopores, a method based on the synergistic effects of low‐temperature microemulsions and Hofmeister ions is developed. Low temperature dramatically enhanced the solubility of hydrophobic solvent in the microemulsion core, enlarging the mesopores in HMMOFs replica. Meanwhile, Hofmeister salt‐in ions continuously controlled mesopore expansion by modulating the permeability of swelling agent into the microemulsion core. The large mesopores up to 33 nm provided sufficient space for the alkaline phosphatase (ALP) enrichment, and retained the remaining channel to facilitate the free mass diffusion. Leveraging these advantages, a colorimetric sensor is successfully developed using large‐mesopore HMMOFs for femtomolar ALP detection based on the enrichment and cycling amplification principles. The sensor exhibited a linear detection range of 100 to 7500 fm and a limit of detection of 42 fm, presenting over 4000 times higher sensitivity than classic para‐nitrophenyl phosphate colorimetric methods. Such high sensitivity highlights the importance of adjustable mesoporous structures of HMMOFs in advanced sensing applications, and prefigures their potential for detecting large biomolecules in diagnostics and biomedical research.

Background: The skeletal muscle index (SMI) can serve as a surrogate for a patient’s nutritional status, which is associated with treatment toxicity. This study aims to investigate the potential of baseline skeletal muscle radiomics features to predict gastrointestinal toxicity of neoadjuvant chemoradiotherapy for rectal cancer. Methods: A total of 214 rectal cancer patients (115, 49 and 50 in the training, internal and external validation set, respectively) who underwent neoadjuvant pelvic radiotherapy with capecitabine and irinotecan were retrospectively identified. The skeletal muscle at the level of the third lumber vertebra was contoured, and the radiomics features were extracted from computed tomography scans. In the training set, the least absolute shrinkage and selection operator (LASSO) regression algorithm was applied to select features that were most significantly associated with grade 3–4 gastrointestinal toxicity (diarrhea, nausea, vomiting and proctitis). The predictive performance and clinical utility were estimated using the area under the receiver operator characteristic curve (AUC), F1-score and decision curve analysis (DCA). Results: Nine features, including the SMI and eight radiomics features, were associated with grade 3–4 gastrointestinal toxicity and included in the logistic regression. This combined predictive model, which incorporated the SMI and radiomics features, showed better discrimination than the SMI alone, with an AUC of 0.856 (95 % CI: 0.782–0.929) in the training cohort, 0.812 (95 % CI: 0.667–0.956) in the internal validation cohort and 0.745 (95 % CI: 0.600–0.890) in the external validation cohort. DCA further verified the clinical utility of the combined predictive model. Conclusion: Radiomics features of skeletal muscle were significantly associated with gastrointestinal toxicity. The predictive model incorporating the SMI and radiomics features exhibits favorable discrimination and may be highly informative for clinical decision-makings.

Abstract Immunotherapy as a rapidly developing therapeutic approach has revolutionized cancer treatment and revitalized the field of tumor immunology research. 3D in vitro models are emerging as powerful tools considering their feature to maintain tumor cells in a near-native state and have been widely applied in oncology research. The novel 3D culture methods including the co-culture of organoids and immune cells, ALI culture, 3D-microfluidic culture and 3D-bioprinting offer new approaches for tumor immunology study and can be applied in many fields such as personalized treatment, immunotherapy optimizing and adoptive cell therapy. In this review, we introduce commonly used 3D in vitro models and summarize their applications in different aspects of tumor immunology research. We also provide a preliminary analysis of the current shortcomings of these models and the outlook of future development.

Non-alcoholic fatty liver disease (NAFLD) is a type of metabolic stress liver injury closely related to insulin resistance (IR) and genetic susceptibility without alcohol consumption, which encompasses a spectrum of liver disorders ranging from simple hepatic lipid accumulation, known as steatosis, to the more severe form of steatohepatitis (NASH). NASH can progress to cirrhosis and hepatocellular carcinoma (HCC), posing significant health risks. As a multisystem disease, NAFLD is closely associated with systemic insulin resistance, central obesity, and metabolic disorders, which contribute to its pathogenesis and the development of extrahepatic complications, such as cardiovascular disease (CVD), type 2 diabetes mellitus, chronic kidney disease, and certain extrahepatic cancers. Recent evidence highlights the indispensable roles of intestinal barrier dysfunction and gut microbiota in the onset and progression of NAFLD/NASH. This review provides a comprehensive insight into the role of intestinal barrier dysfunction and gut microbiota in NAFLD, including intestinal barrier function and assessment, inflammatory factors, TLR4 signaling, and the gut–liver axis. Finally, we conclude with a discussion on the potential therapeutic strategies targeting gut permeability and gut microbiota in individuals with NAFLD/NASH, such as interventions with medications/probiotics, fecal transplantation (FMT), and modifications in lifestyle, including exercise and diet.

For patients with locally recurrent rectal cancer (LRRC), the response rate to chemoradiotherapy is 40%–50%. Additionally, only approximately 40%–50% of patients with recurrent rectal cancer are able to undergo R0 resection. Recent studies in locally advanced rectal cancer (LARC) have shown promising synergistic effects when combining immunotherapy (PD-1/PD-L1 antibodies) with neoadjuvant chemoradiotherapy (nCRT). Therefore, incorporating immunotherapy into the treatment regimen for LRRC patients has the potential to further improve response rates and prognosis. To investigate this, the TORCH-R trial was conducted. This prospective, single-arm, two-cohort, phase II trial focuses on the use of hypofractionated radiotherapy, chemotherapy, and immunotherapy in LRRC patients without or with oligometastases. The trial will include two cohorts: cohort A consists of rectal cancer patients who are treatment-naive for local recurrence, and cohort B includes patients with progressive disease after first-line chemotherapy. Cohort A and cohort B patients will receive 25–40 Gy/5 Fx irradiation or 15–30 Gy/5 Fx reirradiation for pelvic recurrence, respectively. Subsequently, they will undergo 18 weeks of chemotherapy, toripalimab, and stereotactic ablative radiotherapy (SABR) for all metastatic lesions between chemoimmunotherapy cycles. Decisions regarding follow-up of complete response (CR), radical surgery, sustained treatment of non-resection, or exiting the trial are made by a multidisciplinary team (MDT). The primary endpoint of this study is the local objective response rate (ORR). The secondary endpoints include the extrapelvic response rate, duration of response, local recurrence R0 resection rate, progression-free survival (PFS), overall survival (OS), and safety and tolerability. Notably, this trial represents the first clinical exploration of inducing hypofractionated radiotherapy, chemotherapy, and immunotherapy in LRRC patients.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT05628038, identifier NCT05628038.

Background: Acute graft- versus -host disease (aGVHD) is a major complication following hematopoietic stem cell transplantation (HSCT). Objective: This study aimed to explore the risk factors for the incidence of aGVHD in patients post-HSCT. Design: This was a retrospective study. Methods: A total of 407 patients were enrolled. The patients’ data were recorded from the medical records. The exposure of cyclosporine was estimated based on a population pharmacokinetics model. The occurrence of aGVHD was clinically graded and staged in severity from grades I to IV. A proportional odds model that estimated the cumulative probabilities of aGVHD was used to analyze the data using a nonlinear mixed-effects model. Then, the model parameters and plausibility were evaluated by bootstrap and visual predictive checks. Results: The typical probabilities were 18.9% and 17.9% for grade II and grades III–IV, respectively. The incidence of grade II and grade III–IV aGVHD for human leukocyte antigen (HLA) haplo sibling donor patients was higher than that for HLA-matched donor patients. The incidence of grade II and grade III–IV aGVHD decreased with increasing early cyclosporine trough concentration; however, cyclosporine exposure was not associated with the incidence of aGVHD. Conclusion: HLA matching and early cyclosporine trough concentration were important factors for the occurrence of aGVHD.

Introduction Current standard treatment for patients with early rectal cancer is radical surgical resection. Although radical surgery provides effective local tumour control, it also increases the mortality risk and considerable adverse effects, including bowel, bladder, sexual dysfunction and loss of anal function, especially in patients with low-lying rectal cancer. Recent studies have shown promising synergistic effects of the combination of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors and radiotherapy in improving tumour regression. For patients who reach a clinical complete response (cCR) after neoadjuvant therapy, a ‘Watch & Wait’ (W&W) approach can be adopted to preserve anorectal function and improve quality of life. Thus, this study aims to explore the efficacy and safety of radiotherapy combined with chemotherapy and PD-1 antibody in patients with low early rectal cancer.Methods and analysis TORCH-E study is designed as a multicentre, prospective, phase II trial of short-course radiotherapy (SCRT) combined with chemotherapy and PD-1 inhibitor in patients with cT1-3bN0M0 low rectal cancer. The trial was initiated in December 2022 and is currently recruiting patients, with an anticipated completion of participant enrolment by June of the following year. The enrolled 34 patients will receive SCRT (25 Gy/5 Fx), followed by four cycles of capecitabine plus oxaliplatin chemotherapy and PD-1 antibody (toripalimab) and finally receive surgery or the W&W strategy. The primary endpoint is the complete response (CR) rate, that is, the rate of pathological complete response (pCR) plus cCR. The secondary endpoints include organ preservation rate, 3-year local recurrence-free survival rate, 3-year disease-free survival rate, 3-year overall survival rate, grade 3–4 adverse effects rate and patients’ quality of life.Ethics and dissemination This trial has been approved by the Ethics Committee of Fudan University Shanghai Cancer Center. Trial results will be disseminated via peer-reviewed journals and conference presentations.Trial registration number NCT05555888 (ClinicalTrials.gov).

Combination strategies to improve immunotherapy response in microsatellite stable metastatic colorectal cancer (MSS mCRC) remain an unmet need. Several single-arm clinical trials have shown promising synergistic effects between regorafenib and ICIs; however, some contradictory results have also been reported. Randomized controlled trials are needed to further validate the combination of regorafenib with ICIs. In addition, low-dose radiotherapy has been demonstrated to induce local immune responses by reprogramming the tumor microenvironment when combined with high-dose radiotherapy and ICIs. In this study, we designed a prospective, randomized, controlled phase II trial to investigate the efficacy and safety of regorafenib in combination with high/low-dose radiotherapy plus toripalimab in MSS mCRC compared to regorafenib alone. Patients with MSS metastatic adenocarcinoma of the colon or rectum will be enrolled and randomly assigned into two arms: a control arm and an experimental arm. Patients in the control arm will receive regorafenib monotherapy (120 mg once daily on days 1-21 of each 28 days cycle). Patients in the experimental arm will first receive one cycle of regorafenib (80 mg once daily on days 1-21 of each 28 days cycle) and toripalimab (240mg, q3w), followed by high-dose (4-8 fractions of 8-12Gy) and low-dose (1-10Gy at 0.5-2Gy/fraction) radiotherapy, and then continue regorafenib and toripalimab treatment. The primary endpoint is the objective response rate, and the secondary endpoints are disease control rate, duration of remission, median progress-free survival, median overall survival, and adverse events. Recruitment started in August 2023 and is ongoing.Clinical Trial Registrationhttps://clinicaltrials.gov/study/NCT05963490?cond=NCT05963490&rank=1, identifier NCT05963490.

The therapeutic and pharmacological potential of isoliquiritigenin has been reported in relieving inflammation and lipid metabolism disorders, particularly in the context of non-alcoholic fatty liver disease (NAFLD). The aim of this study is to investigate the effects of isoliquiritigenin on NAFLD, obesity-associated metabolic symptoms in vivo and in vitro, and explore new mechanisms underlying its effects. Our study revealed that isoliquiritigenin effectively reduced lipid accumulation and suppressed inflammation factors expression in hepatocytes and high fat diet (HFD) mice. Additionally, it prevented body weight gain and liver damage in HFD mice. Importantly, RNA-sequencing results revealed that isoliquiritigenin exerts its anti-NAFLD effect may through the mTOR pathway and autophagy. Rescue experiments further confirmed that it inhibits inflammation by suppressing the PI3K/AKT/mTOR pathway and reduces lipid accumulation by promoting autophagy. Therefore, it holds promise as a novel treatment for NAFLD.

Background: The watch-and-wait (W&W) strategy is a novel treatment option for patients with rectal cancer who have a strong desire for organ preservation. The study aimed to explore the long-term outcomes of the W&W strategy in a large cohort of rectal cancer patients who achieved a clinical complete response (cCR) after consolidation total neoadjuvant therapy (TNT), and to compare with patients who achieved a pathological complete response (pCR) after radical surgery. Methods: The W&W group comprised patients who were assessed as having a cCR after consolidation TNT and adopted the W&W strategy. Patients who underwent standard resection and achieved a pCR were compared as a reference. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan–Meier analysis with log-rank test was used to compare survival outcomes. Results: We included 89 and 171 patients in the W&W and pCR groups, respectively. The median follow-up period was 45 and 58 months for the W&W and pCR groups, respectively. After IPTW adjustment, the 2-year local regrowth/recurrence rate for the W&W and pCR groups were 9.9% and 2.0%, respectively ( p < 0.001). The W&W and pCR groups had similar 5-year outcomes, including overall survival, disease-free survival, and distant metastasis-free survival (all p > 0.05). No significant difference was observed in the rates of distant metastasis between patients in the W&W group with local regrowth and those without local regrowth (25% versus 6.2%, p = 0.119). Conclusion: Patients who were managed with a W&W strategy after consolidation TNT had favorable survival outcomes, which were similar to those of patients with a pCR. The rate of local regrowth in W&W patients was lower in our study than in other studies as a result of the implementation of consolidation TNT.

Abstract Background Neonatal health is a cornerstone for the healthy development of the next generation and a driving force for the progress of population and society in the future. Updated information on the burden of neonatal disorders (NDs) are of great importance for evidence-based health care planning in China, whereas such an estimate has been lacking at national level. This study aims to estimate the temporal trends and the attributable burdens of selected risk factors of NDs and their specific causes in China from 1990 to 2019, and to predict the possible trends between 2020 and 2024. Methods Data was explored from the Global Burden of Disease study (GBD) 2019. Six measures were used: incidence, mortality, prevalence, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs). Absolute numbers and age-standardized rates (with 95% uncertainty intervals) were calculated. The specific causes of NDs mainly included neonatal preterm birth (NPB), neonatal encephalopathy due to birth asphyxia and trauma (NE), neonatal sepsis and other neonatal infections (NS), and hemolytic disease and other neonatal jaundice (HD). An autoregressive integrated moving average (ARIMA) model was used to forecast disease burden from 2020 to 2024. Results There were notable decreasing trends in the number of deaths (84.3%), incidence (30.3%), DALYs (73.5%) and YLLs (84.3%), while increasing trends in the number of prevalence (102.3%) and YLDs (172.7%) from 1990 to 2019, respectively. The corresponding age-standardized rates changed by -74.9%, 0.1%, -65.8%, -74.9%, 86.8% and 155.1%, respectively. Four specific causes of NDs followed some similar and different patterns. The prediction results of the ARIMA model shown that all measures still maintained the original trends in the next five years. Low birth weight, short gestation, ambient particulate matter pollution and household air pollution from solid fuels were the four leading risk factors. Conclusion The health burden due to NDs is declining and is likely to continue to decline in the future in China. Delaying the increasing burden of disability may be the next target of concern. Targeted prevention and control strategies for specific causes of NDs are urgently needed to reduce the disease burden.

Highlights 1. High-throughput screening of ATG4B inhibitors based on FDA-approved drug library 2. Ebselen can covalently bind to ATG4B at Cys74 3. Ebselen can promote ATG4B oligomerization at Cys292 and Cys361 4. Ebselen suppresses the growth of colorectal cancer cells and xenograft tumors via ATG4B inhibition

High-speed flexible circuits are essential in flexible systems for real-time information analysis and wireless communication. Here, flexible circuits are reported with a 281 ps stage delay based on scaled carbon nanotube thin film transistors.

Abstract Gene fusions can drive tumor development for multiple types of cancer. Currently, many drugs targeting gene fusions are being approved for clinical application. At present, tyrosine receptor kinase (TRK) inhibitors targeting neurotrophic tyrosine receptor kinase (NTRK) gene fusions are among the first “tumor agnostic” drugs approved for pan‐cancer use. Representative TRK inhibitors, including larotrectinib and entrectinib, have shown high efficacy for many types of cancer. At the same time, several second‐generation drugs designed to overcome first‐generation drug resistance are undergoing clinical development. Due to the rarity of NTRK gene fusions in common cancer types and technical issues regarding the complexity of fusion patterns, effectively screening patients for TRK inhibitor treatment in routine clinical practice is challenging. Different detection methods including immunohistochemistry, fluorescence in situ hybridization, reverse transcription‐polymerase chain reaction, and (DNA and/or RNA‐based) next‐generation sequencing have pros and cons. As such, recommending suitable tests for individual patients and ensuring the quality of tests is essential. Moreover, at present, there is a lack of systematic review for the clinical efficacy and development status of first‐ and second‐generation TRK inhibitors. To resolve the above issues, our expert group has reached a consensus regarding the diagnosis and treatment of NTRK gene fusion solid tumors, aiming to standardize clinical practice with the goal of benefiting patients with NTRK gene fusions treated with TRK inhibitors.

Abstract Background Script-based planning and knowledge-based planning are two kinds of automatic planning solutions. Hybrid automatic planning may integrate the advantages of both solutions and provide a more robust automatic planning solution in the clinic. In this study, we evaluated and compared a commercially available hybrid planning solution with manual planning and script-based planning. Methods In total, 51 rectal cancer patients in our institution were enrolled in this study. Each patient generated 7 plans: one clinically accepted manual plan ( $${plan}_{manual}$$ plan manual ), three script-based plans and three hybrid plans generated with the volumetric-modulated arc therapy technique and 3 different clinical goal settings: easy, moderate and hard ( $${plan}_{hybrid}^{easy}$$ plan hybrid easy , $${plan}_{hybrid}^{moderate}$$ plan hybrid moderate , $${plan}_{hybrid}^{hard}$$ plan hybrid hard , $${plan}_{script}^{easy}$$ plan script easy , $${plan}_{script}^{moderate}$$ plan script moderate and $${plan}_{script}^{hard}$$ plan script hard ). Planning goals included planning target volume (PTV) Dmax, bladder Dmean and femur head Dmean. The PTV prescription was the same (50.00 Gy) for the 3 goal settings. The hard setting required a lower PTV Dmax and stricter organ at risk (OAR) dose, while the easy setting was the opposite. Plans were compared using dose metrics and plan quality metric (PQM) scores, including bladder D15 and D50, left and right femur head D25 and D40, PTV D2, D98, CI (conformity index) and HI (homogeneity index). Results Compared to manual planning, hybrid planning with all settings significantly reduced the OAR dose (p

Abstract Background Tumor deposits (TDs) have been identified as an independent prognostic factor in gastric cancer (GC). However, the associated clinicopathological factors and how to simply and reasonably incorporate TD into the TNM staging system remain undetermined. The aim of the current study was therefore to assess the significance of TD among radically resected GC patients. Methods We retrospectively reviewed 1915 patients undergoing radical resection between 2007 and 2012. The patients were classified into two groups according to TD status (absent vs. present), and the clinicopathologic characteristics, DFS, and OS were compared. Associations of TD presence with other clinicopathologic factors were evaluated by logistic regression analysis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic factors for DFS and OS in the primary cohort. Propensity score matching (PSM) was performed to reduce the possibility of selection bias according to the presence of TD. External validation of previously proposed modified staging systems incorporating TD was conducted. Results The detection rate of TD was 10.5% (201/1915). The presence of TD was significantly related to unfavorable clinicopathologic variables, including advanced T and N categories. According to the multivariate Cox regression analysis, the presence of TD was identified as an independent prognostic factor for DFS and OS in the primary cohort (both P < 0.001). In the after-PSM cohort, TD presence also significantly shortened DFS and OS. In the external validation, one system that incorporated TD into the pTNM stage had the best performance. Conclusions The presence of TD was significantly associated with poor survival in radically resected GC patients. The incorporation of TD into the TNM staging system can further improve the predictive capability. A multicenter cohort with a large sample size is needed to determine the appropriate method of incorporation.

Abstract Nanozymes, featuring intrinsic biocatalytic effects and broad‐spectrum antimicrobial properties, are emerging as a novel antibiotic class. However, prevailing bactericidal nanozymes face a challenging dilemma between biofilm penetration and bacterial capture capacity, significantly impeding their antibacterial efficacy. Here, this work introduces a photomodulable bactericidal nanozyme (ICG@hMnOx), composed of a hollow virus‐spiky MnOx nanozyme integrated with indocyanine green, for dually enhanced biofilm penetration and bacterial capture for photothermal‐boosted catalytic therapy of bacterial infections. ICG@hMnOx demonstrates an exceptional capability to deeply penetrate biofilms, owing to its pronounced photothermal effect that disrupts the compact structure of biofilms. Simultaneously, the virus‐spiky surface significantly enhances the bacterial capture capacity of ICG@hMnOx. This surface acts as a membrane‐anchored generator of reactive oxygen species and a glutathione scavenger, facilitating localized photothermal‐boosted catalytic bacterial disinfection. Effective treatment of methicillin‐resistant Staphylococcus aureus‐associated biofilm infections is achieved using ICG@hMnOx, offering an appealing strategy to overcome the longstanding trade‐off between biofilm penetration and bacterial capture capacity in antibacterial nanozymes. This work presents a significant advancement in the development of nanozyme‐based therapies for combating biofilm‐related bacterial infections.

Background: The role of body mass index (BMI) in the treatment outcomes of lymphoma patients is controversial. While investigating the efficacy of ABVD-like regimen in Hodgkin lymphoma (HL) patients, we observed that obese patients had poor responses. To better understand this clinical phenomenon, we evaluated the effect of BMI on responses to ABVD-like chemotherapy in HL patients.Methods: This retrospective cohort study evaluated the clinical outcomes of all 67 patients with confirmed HL who were treated at the First Affiliated Hospital of Soochow University from November 2016 to March 2023 with an ABVD-like regimen as first-line chemotherapy. Baseline patient characteristics and clinical outcomes were compared across different BMI categories. The primary end-point was the overall response rate defined as the proportion of the HL patients who achieved complete response or partial response. The additional end-points included progression-free survival and overall survival.Results: The median age of the HL patients was 31 years old. Of the patients, 10.4% were obese, and 17.9% patients were overweight. Interim and end-term response evaluations revealed overall response rates of 98.5% and 83.6%, respectively. The proportion of patients with potential poor prognostic factors (IPS risk factors) did not differ significantly in the responders versus non-responders. However, non-responders had a higher average BMI when compared with responders (p = 0.002). Poor overall response rates in higher BMI patients indeed manifested with shorter progression free survival (p = 0.013). The minimum relative dose of the ABVD-like regimen in the overweight and obese groups was significantly lower than in the normal weight group (p < 0.001).Conclusion: Our analyses show that >80% of newly-diagnosed HL patients responded to the ABVD-like regimen. We find that being obese or overweight at the time of diagnosis correlated with a poorer overall response rate and that BMI was an independent risk factor in HL patients treated with the ABVD-like regimen. Lower doses of ABVD-like regimen contributed to the discrepant findings of responses in the high BMI groups. These findings indicate that newly-diagnosed, obese HL patients receiving an ABVD-like regimen require personalized treatment.

Optical coherence tomography (OCT) is a revolutionary imaging technology in the field of ophthalmic medical imaging [...]