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Sisi Mo,1– 3,* Haiming Ru,1– 3,* Maosen Huang,1– 3 Linyao Cheng,1– 3 Xianwei Mo,1– 3 Linhai Yan1– 3 1Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Guangxi Clinical Research Center for Colorectal Cancer, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 3Guangxi Key Laboratory of Colorectal Cancer Prevention and Treatment, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linhai YanDepartment of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Hedi Road No. 71, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Tel +86 139 78839969, Email lhyan@gxmu.edu.cnAbstract: It is widely recognized that microbial disorders are involved in the pathogenesis of many malignant tumors. The oral and intestinal tract are two of the overriding microbial habitats in the human body. Although they are anatomically and physiologically continuous, belonging to the openings at both ends of the digestive tract, the oral and intestinal microbiome do not cross talk with each other due to a variety of reasons, including intestinal microbial colonization resistance and chemical barriers in the upper digestive tract. However, this balance can be upset in certain circumstances, such as disruption of colonization resistance of gut microbes, intestinal inflammation, and disruption of the digestive tract chemical barrier. Evidence is now accruing to suggest that the oral microbiome can colonize the gut, leading to dysregulation of the gut microbes. Furthermore, the oral-gut microbes create an intestinal inflammatory and immunosuppressive microenvironment conducive to tumorigenesis and progression of colorectal cancer (CRC). Here, we review the oral to intestinal microbial transmission and the inflammatory and immunosuppressive microenvironment, induced by oral-gut axis microbes in the gut. A superior comprehension of the contribution of the oral-intestinal microbes to CRC provides new insights into the prevention and treatment of CRC in the future.Keywords: oral-intestinal microbiota, colorectal cancer, inflammatory microenvironment, immunosuppressive microenvironment

Abstract Anaplastic thyroid cancer (ATC) is among the most aggressive and metastatic malignancies, often resulting in fatal outcomes due to the lack of effective treatments. Prosapogenin A (PA), a bioactive compound prevalent in traditional Chinese herbs, has shown potential as an antineoplastic agent against various human tumors. However, its effects on ATC and the underlying mechanism remain unclear. Here, we demonstrate that PA exhibits significant anti-ATC activity both in vitro and in vivo by inducing GSDME-dependent pyroptosis in ATC cells. Mechanistically, PA promotes lysosomal membrane permeabilization (LMP), leading to the release of cathepsins that activate caspase 8/3 to cleave GSDME. Remarkably, PA significantly upregulates three key functional subunits of V-ATPase—ATP6V1A, ATP6V1B2, and ATP6V0C—resulting in lysosomal over-acidification. This over-acidification exacerbates LMP and subsequent lysosomal damage. Neutralization of lysosomal lumen acidification or inhibition/knockdown of these V-ATPase subunits attenuates PA-induced lysosomal damage, pyroptosis and growth inhibition of ATC cells, highlighting the critical role for lysosomal acidification and LMP in PA’s anticancer effects. In summary, our findings uncover a novel link between PA and lysosomal damage-dependent pyroptosis in cancer cells. PA may act as a V-ATPase agonist targeting lysosomal acidification, presenting a new potential therapeutic option for ATC treatment.

Objective: This study compares endoscopic thyroidectomy by gasless unilateral axillary approach (ETGUA) and sternocleidomastoid leading-edge approach (SLEA) with conventional open thyroidectomy (COT) in hemithyroidectomy. The main focus is on the protection of neck muscles (sternocleidomastoid, omohyoid, sternothyroid) and the postoperative function of voice and swallowing yielded through these common approaches. Methods: A total of 302 patients who underwent hemithyroidectomy were enrolled and divided into three groups: ETGUA (n = 101), SLEA (n = 100), and COT (n = 101). Ultrasound was used to measure the thickness of bilateral neck muscles, including the sternocleidomastoid, omohyoid, and sternothyroid. The changes in thickness on the surgical side compared to the non-surgical side. Analyzed factors included muscle thickness changes, Swallowing Impairment Score (SIS), Voice Handicap Index (VHI), Scar Cosmesis Assessment and Rating (SCAR), Neck Injury Index (NII), surgery duration, drainage volume, hospitalization, and number of lymph nodes. Results: The clinical characteristics among the three groups were consistent except for differences in sex, age, and BMI. Metrics such as sternocleidomastoid muscle, NII, hypocalcemia, postoperative PTH, transient hoarseness, and number of lymph nodes showed no significant differences among the three groups. However, significant differences were found in the duration of surgery, drainage volume, hospitalization period omohyoid muscle, Sternohyoid muscle, VHI, SIS, and SCAR (all p

Melanoma, a malignant skin cancer arising from melanocytes, exhibits rapid metastasis and a high mortality rate, especially in advanced stages. Current treatment modalities, including surgery, radiation, and immunotherapy, offer limited success, with immunotherapy using immune checkpoint inhibitors (ICIs) being the most promising. However, the high mortality rate underscores the urgent need for robust, non-invasive biomarkers to predict patient response to adjuvant therapies. The immune microenvironment of melanoma comprises various immune cells, which influence tumor growth and immune response. Melanoma cells employ multiple mechanisms for immune escape, including defects in immune recognition and epithelial-mesenchymal transition (EMT), which collectively impact treatment efficacy. Single-cell analysis technologies, such as single-cell RNA sequencing (scRNA-seq), have revolutionized the understanding of tumor heterogeneity and immune microenvironment dynamics. These technologies facilitate the identification of rare cell populations, co-expression patterns, and regulatory networks, offering deep insights into tumor progression, immune response, and therapy resistance. In the realm of biomarker discovery for melanoma, single-cell analysis has demonstrated significant potential. It aids in uncovering cellular composition, gene profiles, and novel markers, thus advancing diagnosis, treatment, and prognosis. Additionally, tumor-associated antibodies and specific genetic and cellular markers identified through single-cell analysis hold promise as predictive biomarkers. Despite these advancements, challenges such as RNA-protein expression discrepancies and tumor heterogeneity persist, necessitating further research. Nonetheless, single-cell analysis remains a powerful tool in elucidating the mechanisms underlying therapy response and resistance, ultimately contributing to the development of personalized melanoma therapies and improved patient outcomes.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease characterized by intestinal barrier dysfunction, inflammatory synergistic effects and excessive tissue injury. Gallic acid (GA) is renowned for its remarkable biological activity, encompassing anti-inflammatory and antioxidant properties. However, the underlying mechanisms by which GA protects against intestinal inflammation have not been fully elucidated. The aim of this study is to investigate the effect of GA on the inflammation of a lipopolysaccharide (LPS)-stimulated human colon carcinoma cell line (Caco-2) and on the intestinal barrier dysfunction, and explore the underlying molecular mechanism involved. Our findings demonstrate that 5 μg/mL GA restores the downregulation of the mRNA and protein levels of Claudin-1, Occludin, and ZO-1 and decreases the expressions of inflammatory factors such as IL-6, IL-1β and TNF-α induced by LPS. In addition, GA exhibits a protective effect by reducing the LPS-enhanced early and late apoptotic ratios, downregulating the mRNA levels of pro-apoptotic factors (Bax, Bad, Caspase-3, Caspase-8, and Caspase-9), and upregulating the mRNA levels of anti-apoptotic factor Bcl-2 in Caco-2 cells. GA also reduces the levels of reactive oxygen species increased by LPS and restores the activity of antioxidant enzymes, namely, superoxide dismutase and catalase, as well as the level of glutathione. More importantly, GA exerts its anti-inflammatory effects by inhibiting the LPS-induced phosphorylation of key signaling molecules in the NF-κB/MAPK pathway, including p65, IκB-α, p38, JNK, and ERK, in Caco-2 cells. Overall, our findings show that GA increases the expressions of tight junction proteins, reduces cell apoptosis, relieves oxidative stress and suppresses the activation of the NF-κB/MAPK pathway to reduce LPS-induced intestinal inflammation in Caco-2 cells, indicating that GA has potential as a therapeutic agent for intestinal inflammation.

Abstract Introduction Herpes zoster (HZ) can cause substantial patient morbidity and lead to large healthcare costs. However, the disease burden of HZ in Southeast Asia may be underestimated. This study aimed to estimate the public health burden of HZ and the impact of vaccinating adults aged ≥ 50 years old in five Southeast Asian countries (Indonesia, Malaysia, Philippines, Thailand, and Vietnam), with adjuvanted recombinant zoster vaccine (RZV) compared with no vaccination. Methods For each country, we adapted a static multicohort Markov model developed with a 1-year cycle length and lifetime horizon. Demographics were obtained from the World Health Organization, HZ incidence from a worldwide meta-regression reporting Asian-specific values, proportions of postherpetic neuralgia (PHN) and non-PHN complications from local/regional studies, and vaccine efficacy from a long-term follow-up trial. First-dose coverage and second-dose compliance were assumed to be 30% and 70%, respectively. A one-way deterministic sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA) were performed to assess the robustness and uncertainty of inputs for each country. Results Without RZV, it was estimated that there would be a total of approximately 10 million HZ cases, 2.1 million PHN cases, and 1.4 million non-PHN complications in individuals aged ≥ 50 years included in the model. Introducing RZV under 30% coverage could avoid approximately 2.2 million (22%) HZ cases, almost 500,000 (21%) PHN cases, and around 300,000 (22%) non-PHN complications. OWSA showed that first-dose coverage and initial HZ incidence had the largest impact on the estimated number of HZ cases avoided. The number needed to vaccinate ranged from 15 to 21 to prevent one case of HZ and from 68 to 104 to prevent one case of PHN across each country. Conclusions This study demonstrated that there is substantial HZ disease burden in older adults for the five selected countries in Southeast Asia, negatively impacting national healthcare systems. Introducing RZV could potentially reduce this burden. A graphical abstract is available with this article. Graphical Abstract

Abstract Conventional circuit elements are constrained by limitations in area and power efficiency at processing physical signals. Recently, researchers have delved into high-order dynamics and coupled oscillation dynamics utilizing Mott devices, revealing potent nonlinear computing capabilities. However, the intricate yet manageable population dynamics of multiple artificial sensory neurons with spatiotemporal coupling remain unexplored. Here, we present an experimental hardware demonstration featuring a capacitance-coupled VO2 phase-change oscillatory network. This network serves as a continuous-time dynamic system for sensory pre-processing and encodes information in phase differences. Besides, a decision-making module for special post-processing through software simulation is designed to complete a bio-inspired dynamic sensory system. Our experiments provide compelling evidence that this transistor-free coupling network excels in sensory processing tasks such as touch recognition and gesture recognition, achieving significant advantages of fewer devices and lower energy-delay-product compared to conventional methods. This work paves the way towards an efficient and compact neuromorphic sensory system based on nano-scale nonlinear dynamics.

Abstract Objective Metabolic risks play a key role in the progression of pancreatic cancer. This study aimed to present global, regional and national data on mortality and disability-adjusted life-year (DALY) for pancreatic cancer attributable to metabolic risk and to forecast mortality to 2030 using data from the Global Burden of Disease (GBD). Methods Data on mortality and DALYs due to pancreatic cancer attributable to metabolic risks were obtained from GBD 2019. Metabolic risks include high fasting plasma glucose (FPG) and high body mass index (BMI). Total numbers and age-standardized rates per 100,000 people for mortality and DALYs were reported by age, sex, region and country/territory from 1990 to 2019. The “Bayes age-period-cohort” method was used for projections of mortality to 2030. Results Globally, there was a 3.5-fold increase in the number of pancreatic cancer deaths attributable to metabolic risk, from 22,091 in 1990 to 77,215 in 2019. High-income North America and Central Europe had the highest age-standardized mortality rates (ASMRs) of pancreatic cancer attributable to high FPG and high BMI in 2019, respectively. From 1990 to 2019, the global ASMR of pancreatic cancer attributable to high FPG and high BMI increased. Countries with high healthcare access quality had much higher age-standardized DALY rates. In the next 10 years, the ASMR of pancreatic cancer attributable to high FPG and high BMI will continue to increase. Conclusion Pancreatic cancer mortality and DALYs attributable to metabolic factors remain high, particularly in high-income regions or countries. Studies on the metabolic mechanism of pancreatic cancer and effective treatment strategies are needed.

Field-effect transistors (FETs) switched by quantum band-to-band tunneling (BTBT) mechanism, rather than conventional thermionic emission mechanism, are emerging as an exciting device candidate for future ultralow-power electronics due to their exceptional electronic properties of subthermionic subthreshold swing. However, fundamental limitations in drive current have hindered such technology encountering for high-performance and high-speed operations, especially for silicon-based device. Here, we demonstrate a novel pathway of integrating tunneling and thermionic emission mechanisms together, to circumvent their respective limitation and design a hybrid adaptively modulated FET (HamFET) that orients power saving and performance enhancement simultaneously. This transistor architecture, utilizing a nested source configuration without cost or area penalties, exhibits both ultrasteep (subthermionic) subthreshold swing and the largest “on” and “off” current ratio over the state-of-the-art tunneling transistors. Our design methodology of hybrid switching mechanism is also applicable to other mechanism, material, and architecture systems, opening the doors to a range of high-speed application opportunities for ultralow-power but performance-insufficient electronics.

Cancer remains a significant global challenge, with escalating incidence rates and a substantial burden on healthcare systems worldwide. Herein, we present an in-depth exploration of the intricate interplay between cancer cell death pathways and tumor immunity within the tumor microenvironment (TME). We begin by elucidating the epidemiological landscape of cancer, highlighting its pervasive impact on premature mortality and the pronounced burden in regions such as Asia and Africa. Our analysis centers on the pivotal concept of immunogenic cell death (ICD), whereby cancer cells succumbing to specific stimuli undergo a transformation that elicits robust anti-tumor immune responses. We scrutinize the mechanisms underpinning ICD induction, emphasizing the release of damage-associated molecular patterns (DAMPs) and tumor-associated antigens (TAAs) as key triggers for dendritic cell (DC) activation and subsequent T cell priming. Moreover, we explore the contributions of non-apoptotic RCD pathways, including necroptosis, ferroptosis, and pyroptosis, to tumor immunity within the TME. Emerging evidence suggests that these alternative cell death modalities possess immunogenic properties and can synergize with conventional treatments to bolster anti-tumor immune responses. Furthermore, we discuss the therapeutic implications of targeting the TME for cancer treatment, highlighting strategies to harness immunogenic cell death and manipulate non-apoptotic cell death pathways for therapeutic benefit. By elucidating the intricate crosstalk between cancer cell death and immune modulation within the TME, this review aims to pave the way for the development of novel cancer therapies that exploit the interplay between cell death mechanisms and tumor immunity and overcome Challenges in the Development and implementation of Novel Therapies.

IntroductionFreshwater ecosystems are susceptible to invasion by alien macrophytes due to their connectivity and various plant dispersal vectors. These ecosystems often experience anthropogenic nutrient enrichment, favouring invasive species that efficiently exploit these resources. Propagule pressure (reflecting the quantity of introduced individuals) and habitat invasibility are key determinants of invasion success. Moreover, the enemy release hypothesis predicts that escape from natural enemies, such as herbivores, allows alien species to invest more resources to growth and reproduction rather than defense, enhancing their invasive potential. Yet, the combined impact of propagule pressure, herbivory, and nutrient enrichment on the competitive dynamics between invasive alien macrophytes and native macrophyte communities is not well understood due to a paucity of studies.MethodsWe conducted a full factorial mesocosm experiment to explore the individual and combined effects of herbivory, nutrient levels, propagule pressure, and competition on the invasion success of the alien macrophyte Myriophyllum aquaticum into a native macrophyte community comprising Vallisneria natans, Hydrilla verticillata, and Myriophyllum spicatum. This setup included varying M. aquaticum densities (low vs. high, simulating low and high propagule pressures), two levels of herbivory by the native snail Lymnaea stagnalis (herbivory vs no-herbivory), and two nutrient conditions (low vs. high). Myriophyllum aquaticum was also grown separately at both densities without competition from native macrophytes. ResultsThe invasive alien macrophyte M. aquaticum produced the highest shoot and total biomass when simultaneously subjected to conditions of high-density intraspecific competition, no herbivory, and low-nutrient availability treatments. Moreover, a high propagule pressure of M. aquaticum significantly reduced the growth of the native macrophyte community in nutrient-rich conditions, but this effect was not observed in nutrient-poor conditions. DiscussionThese findings indicate that M. aquaticum has adaptive traits enabling it to flourish in the absence of herbivory (supporting the enemy release hypothesis) and in challenging environments such as intense intraspecific competition and low nutrient availability. Additionally, the findings demonstrate that when present in large numbers, M. aquaticum can significantly inhibit the growth of native macrophyte communities, particularly in nutrient-rich environments. Consequently, reducing the propagule pressure of M. aquaticum could help control its spread and mitigate its ecological impact. Overall, these findings emphasize that the growth and impacts of invasive alien plants can vary across different habitat conditions and is shaped by the interplay of biotic and abiotic factors.

The β3-adrenoceptor agonist mirabegron is available for the treatment of storage symptoms of overactive bladder, including frequency, urgency, and incontinence. The off-target effects of mirabegron include binding to α1-adrenoceptors, which are central in the treatment of voiding symptoms. Here, we examined the structure–function relationships in the binding of mirabegron to a cryo-electron microscopy structure of α1A. The binding was simulated by docking mirabegron to a 3D structure of a human α1A-adrenoceptor (7YMH) using Autodock Vina. The simulations identified two binding states: slope orientation involving 10 positions and horizontal binding to the receptor surface involving 4 positions. No interactions occurred with positions constituting the α1A binding pocket, including Asp-106, Ser-188, or Phe-312, despite the positioning of the phenylethanolamine moiety in transmembrane regions close to the binding pocket by contact with Phe-288, -289, and Val-107. Contact with the unique positions of α1A included the transmembrane Met-292 during slope binding and exosite Phe-86 during horizontal binding. Exosite binding in slope orientation involved contact of the anilino part, rather than the aminothiazol end, to Ile-178, Ala-103, and Asn-179. In conclusion, contact with Met-292 and Phe-86, which are unique positions of α1A, accounts for mirabegron binding to α1A. Because of its lack of interactions with the binding pocket, mirabegron has lower affinity compared to α1A-blockers and no effects on voiding symptoms.

Colorectal cancer (CRC), known for its high metastatic potential, remains a leading cause of cancer-related death. This review emphasizes the critical role of immune responses in CRC metastasis, focusing on the interaction between immune cells and tumor microenvironment. We explore how immune cells, through cytokines, chemokines, and growth factors, contribute to the CRC metastasis cascade, underlining the tumor microenvironment’s role in shaping immune responses. The review addresses CRC’s immune evasion tactics, especially the upregulation of checkpoint inhibitors like PD-1 and CTLA-4, highlighting their potential as therapeutic targets. We also examine advanced immunotherapies, including checkpoint inhibitors and immune cell transplantation, to modify immune responses and enhance treatment outcomes in CRC metastasis. Overall, our analysis offers insights into the interplay between immune molecules and the tumor environment, crucial for developing new treatments to control CRC metastasis and improve patient prognosis, with a specific focus on overcoming immune evasion, a key aspect of this special issue.

Abstract Radiation tolerance is determined as the ability of crystalline materials to withstand the accumulation of the radiation induced disorder. Nevertheless, for sufficiently high fluences, in all by far known semiconductors it ends up with either very high disorder levels or amorphization. Here we show that gamma/beta (γ/β) double polymorph Ga2O3 structures exhibit remarkably high radiation tolerance. Specifically, for room temperature experiments, they tolerate a disorder equivalent to hundreds of displacements per atom, without severe degradations of crystallinity; in comparison with, e.g., Si amorphizable already with the lattice atoms displaced just once. We explain this behavior by an interesting combination of the Ga- and O- sublattice properties in γ-Ga2O3. In particular, O-sublattice exhibits a strong recrystallization trend to recover the face-centered-cubic stacking despite the stronger displacement of O atoms compared to Ga during the active periods of cascades. Notably, we also explained the origin of the β-to-γ Ga2O3 transformation, as a function of the increased disorder in β-Ga2O3 and studied the phenomena as a function of the chemical nature of the implanted atoms. As a result, we conclude that γ/β double polymorph Ga2O3 structures, in terms of their radiation tolerance properties, benchmark a class of universal radiation tolerant semiconductors.

Abstract Background Mouse embryonic stem cells (mESCs) not only retain the property of self-renewal but also have the ability to develop into primordial germ cell-like cells (PGCLCs). However, knowledge about the mechanisms of transcriptional regulation is still limited. Rhox6, a member of the homeobox family that is located on the X chromosome, is highly expressed within PGCLCs in vivo and in vitro. However, the detailed effects of Rhox6 on PGCLC specification and mESC maintenance remain unclear. Results In this study, we found that overexpression of Rhox6 favors the formation of PGCLCs, while depletion of Rhox6 inhibits the generation of PGCLCs. Mechanistically, Rhox6 directly induces the expression of Nanos3 during the specification of PGCLCs. Subsequently, downregulation of Nanos3 expression is sufficient to decrease the ability of Rhox6 to induce PGCLC formation. Moreover, we found that depletion of Rhox6 expression facilitates the self-renewal of mESCs. High-throughput sequencing revealed that suppression of Rhox6 transcription significantly increases the expression of pluripotency genes. Functional studies further demonstrated that Rhox6 directly represses the transcription of Tbx3. Therefore, knockdown of the expression of the latter impairs the self-renewal of mESCs promoted by Rhox6 downregulation. Conclusions Our study reveals that overexpression of Rhox6 is beneficial for PGCLC generation through induction of Nanos3, while downregulation of Rhox6 contributes to mESC self-renewal by increasing Tbx3. These findings help elucidate the early development of mouse embryos.

Abstract Traffic forecasting, as a fundamental and challenging problem of intelligent transportation systems (ITS), has always been the focus of researchers. Nevertheless, accurate traffic forecasting still exists some problems due to the complex spatial‐temporal dependencies and irregularities of traffic flows. Most of the existing methods typically use the spatial adjacency matrix and complicated mechanism to model spatial‐temporal relationships separately, while ignoring the latent spatial‐temporal correlations. In this paper, a novel architecture is proposed named spatial‐temporal correlation graph convolutional networks (STCGCN) for traffic prediction. First, an informative fused graph structure is constructed to better learn the complex spatial‐temporal correlations, which breaks the limitation that the general spatial adjacency matrix cannot reflect temporal correlations. Moreover, spatial‐temporal correlation graph convolution and gated temporal convolution are performed in parallel and they are integrated into a unified layer, which enables capturing both local and global spatial‐temporal dependencies simultaneously. By stacking multiple layers, STCGCN can learn more long‐range spatial‐temporal dependencies. Experimental results on five public traffic datasets demonstrate the effectiveness and robustness of the proposed STCGCN in urban traffic forecasting.

To address the issues of recast layer and heat affected zone (HAZ) in laser processing in the air, a new waterjet-assisted laser scanning machining (WALSM) was adopted. Laser processing experiments were conducted on DD6 single crystal (SC) superalloy plate to study the effects of various parameters on the microgroove and microhole machining quality, efficiency and taper angle. Results show that WALSM process can eliminate the recast layer, decrease the taper angle, and reduce the HAZ thickness with no microcracks. Orthogonal analysis shows that the waterjet velocity and pulse frequency are the most significant factors affecting the efficiency of WALSM. To further improve the machining efficiency of WALSM in a larger depth, a hybrid laser processing and WALSM process were proposed for drilling large depth holes with high machining efficiency, high accuracy and good surface quality. The hybrid machining process holds great potential in drilling shaped cooling holes on the turbine blades in the aviation industry. [ABSTRACT FROM AUTHOR]

A fluorogenic aptamer (FA)-based hybridization chain reaction (HCR) could provide a sensitive and label-free signal amplification method for imaging molecules in living cells. However, existing FA-HCR methods usually face some problems, such as a complicated design and significant background leakage, which greatly limit their application. Herein, we developed an FA-centered HCR (FAC-HCR) method based on a remote toehold-mediated strand displacement reaction. Compared to traditional HCRs mediated by four hairpin probes (HPs) and two HPs, the FAC-HCR displayed significantly decreased background leakage and improved sensitivity. Furthermore, the FAC-HCR was used to test a non-nucleic acid target, apurinic/apyrimidinic endonuclease 1 (APE1), an important BER-involved endonuclease. The fluorescence analysis results confirmed that FAC-HCR can reach a detection limit of 0.1174 U/mL. By using the two HPs for FAC-HCR with polyetherimide-based nanoparticles, the activity of APE1 in living cells can be imaged. In summary, this study could provide a new idea to design an FA-based HCR and improve the performance of HCRs in live cell imaging.

Abstract Physiological signal processing plays a key role in next-generation human-machine interfaces as physiological signals provide rich cognition- and health-related information. However, the explosion of physiological signal data presents challenges for traditional systems. Here, we propose a highly efficient neuromorphic physiological signal processing system based on VO2 memristors. The volatile and positive/negative symmetric threshold switching characteristics of VO2 memristors are leveraged to construct a sparse-spiking yet high-fidelity asynchronous spike encoder for physiological signals. Besides, the dynamical behavior of VO2 memristors is utilized in compact Leaky Integrate and Fire (LIF) and Adaptive-LIF (ALIF) neurons, which are incorporated into a decision-making Long short-term memory Spiking Neural Network. The system demonstrates superior computing capabilities, needing only small-sized LSNNs to attain high accuracies of 95.83% and 99.79% in arrhythmia classification and epileptic seizure detection, respectively. This work highlights the potential of memristors in constructing efficient neuromorphic physiological signal processing systems and promoting next-generation human-machine interfaces.

Introduction This study aimed to investigate the potential role of moxibustion (MOX) in the treatment of lung infection in patients bed-ridden due to osteoporotic fracture of the spine. Material and methods 96 senile patients with pulmonary infection who were bed-ridden due to osteoporotic fracture of the spine were grouped into a MOX (–) group and a MOX (+) group. An animal model was established as a SHAM group, a PRIMED group, a MOX 15’ group and a MOX 30’ group. Results For the patients’ study, we found that the survival rate was higher for patients who received MOX. Moreover, tumor necrosis factor-, interleukin (IL) 1, IL-6 and IL-18 were down-regulated while IL-10 was up-regulated by MOX. MOX time-dependently increased the survival while reducing the bacteria left in infected mice. Conclusions Moxibustion significantly alleviated the inflammatory responses, thus leading to a better survival rate of patients bed-ridden due to osteoporotic fracture of the spine.

This study constructs an evaluation index system based on demand competitiveness, basic competitiveness, industrial agglomeration, industrial competition, industrial innovation, supporting industries, and government policy competitiveness. The study selected 13 provinces with good development of the new energy vehicle (NEV) industry as the sample. Based on the competitiveness evaluation index system, an empirical analysis was conducted to evaluate the development level of the NEV industry in Jiangsu with grey relational analysis and three-way decisions. The results reveal: 1) Under the absolute level of temporal and spatial characteristic attributes, the development of Jiangsu's NEV industry is in a leading position in the country, and the competitiveness level is closer to that of Shanghai and Beijing; 2) Under the incremental level, Jiangsu's incremental level ranks in the upper and middle reaches of 13 provinces, second only to Shanghai; 3) Under the volatility level, Jiangsu's industrial development fluctuates greatly, and the level of volatility lies in the middle reaches of the country. There is a big gap with Shanghai; 4) From the perspective of overall temporal and spatial characteristics, Jiangsu's overall industrial development level is in the first echelon in China, second only to Shanghai and Beijing, indicating that Jiangsu's NEV industry has a relatively good overall development level.

With the technological scaling of metal–oxide–semiconductor field-effect transistors (MOSFETs) and the scarcity of circuit design margins, the characteristics of device reliability have garnered widespread attention. Traditional single-mode reliability mechanisms and modeling are less sufficient to meet the demands of resilient circuit designs. Mixed-mode reliability mechanisms and modeling have become a focal point of future designs for reliability. This paper reviews the mechanisms and compact aging models of mixed-mode reliability. The mechanism and modeling method of mixed-mode reliability are discussed, including hot carrier degradation (HCD) with self-heating effect, mixed-mode aging of HCD and Bias Temperature Instability (BTI), off-state degradation (OSD), on-state time-dependent dielectric breakdown (TDDB), and metal electromigration (EM). The impact of alternating HCD-BTI stress conditions is also discussed. The results indicate that single-mode reliability analysis is insufficient for predicting the lifetime of advanced technology and circuits and provides guidance for future mixed-mode reliability analysis and modeling.

In the electrochemical process, a continuous passivation layer of Mg(OH)2 is formed on the surface of Mg2Ni alloy particles and prevents the penetration of hydrogen atoms, which have a negative impact on the discharge capacity. In this work, Mg2Ni1-xZnx (x = 0, 0.17, or 0.33) rapid quenching alloys were prepared by partially replacing Ni with Zn in order to modify the surface of the alloy with the corrosiveness of Zn in alkaline solution. The microstructure results indicate that Zn doping promotes the corrosion of Mg2Ni alloy in the electrolyte, and many corrosion holes are formed on the surface after the electrochemical process. With the increase of Zn, the charge-transfer reaction resistance (Rct) and polarization resistance (Rp) of the alloy electrode increase from 306.24 and 366.41 mΩ to 508.76 and 526.57 mΩ, respectively, and the corrosion current density (Io) decreases from 70.08 to 48.77 mA/g. The appropriate amount of Zn atoms increases the discharge capacity, and the highest value can reach 92.94 mAh/g at x = 0.33. This reveals that corrosion holes are formed on the surface of Zn-doped alloys during the electrochemical process and destroy the continuity of the passivation layer on the Mg2Ni surface, which facilitate the penetration of hydrogen atoms.

Conventional vision systems suffer from lots of data handling between memory and processing units. Inspired by how humans recognize noisy images and the flexible modulation on the timescale of ion dynamics inside an emerging memtransistor, a novel neuromorphic vision system is reported based on the ion‐modulated memtransistors. By controlling the ion‐doping processes under adequate stimuli strengths, both short‐term and long‐term ion dynamics can be utilized to deliver energy‐efficient data processing. When dealing with image reconstructions, the short‐term accumulation effect of the device can help filter noises in a set of received noisy images while enhancing the original pattern information. The increased contrast can help distinguish the actual contents. To demonstrate systematic performances with the reconfiguration of devices, the nonlinear relationship between channel conductance variation and the amplitude of gate pulses into the network‐level simulation is extracted. Also, with the nonvolatile conductance change characteristic, the task of recognizing noisy images is performed to verify the versatility of ion‐modulated memtransistors in the neuromorphic artificial vision systems. An interactive preprint version of the article can be found here: https://doi.org/10.22541/au.167939089.96499861/v1

Coronavirus disease 2019 (COVID-19) is causing a serious impact on the people living in countries across the entire world. The spread of this pandemic globally has led people worry every day about losing their jobs or even being threatened by the virus. This pandemic caused people to experience more serious psychological problems than we realized. However, there has been little research on how COVID-19 affects the mental health of the people. In this article, we attempted to use the social text data about COVID-19 on Sina Weibo (the largest “tweet” platform in China, and we will also call Weibo as tweet in the following content), to explore the impact of COVID-19 on the mental health of Chinese people. First, we fifilter the tweet data by selecting examples that contain COVID-19 and COVID-19 correlated keywords. However, we segment the filtered tweets, extract meaningful words, and construct a word vector sparse matrix as the measurement of every tweet. Then, for the model's labels, we use sentiment knowledge enhanced pre-training model (SKEP), a deep learning framework published by Baidu that measures the user's mental state. Through SKEP, we can obtain the probabilities of the user's positive and negative mental states. Finally, we use the XGBoost algorithm to study the relationship between the word vector sparse matrix and the mental health state of users. Our research shows that social text data can, indeed, reflect the mental health state of users to a large extent, and social data can be used to explore the impact of COVID-19 on mental health, which can help frame the public health policy.

Designing an efficient multi-agent hardware system to solve large-scale computational problems through high-parallelism processing with nonlinear interactions remains a challenge. Here, the authors demonstrate that a multi-agent hardware system deploying distributed Ag nanoclusters as physical agents enables parallel, complex computing.

A highly efficient hardware element capable of sensing and encoding multiple physical signals is still lacking. Here, the authors report a spike-based neuromorphic perception system consisting of tunable and highly uniform artificial sensory neurons based on epitaxial VO2 capable of hand gesture classification.

Pancreatic cancer is a strongly malignant gastrointestinal carcinoma characterized by late detection, high mortality rates, poor patient prognosis and lack of effective treatments. Consequently, there is an urgent need to identify novel therapeutic strategies for this disease. Pancreatic stellate cells, which constitute a significant component of the mesenchymal cellular layer within the pancreatic tumor microenvironment, play a pivotal role in modulating this environment through their interactions with pancreatic cancer cells. This paper reviews the mechanisms by which pancreatic stellate cells inhibit antitumor immune responses and promote cancer progression. We also discuss preclinical studies focusing on these cells, with the goal of providing some theoretical references for the development of new therapeutic approaches for pancreatic cancer.

Background: NUAKs promote myosin light chain phosphorlyation, actin organization, proliferation and suppression of cell death in non-muscle cells, which are critical for smooth muscle contraction and growth. In benign prostatic hyperplasia (BPH), contraction and growth in the prostate drive urethral obstruction and voiding symptoms. However, a role of NUAKs in smooth muscle contraction or prostate functions are unknown. Here, we examined effects of NUAK silencing and the presumed NUAK inhibitors, HTH01-015 and WZ4003 on contraction and growth-related functions in prostate stromal cells (WPMY-1) and in human prostate tissues.Methods: Effects of NUAK1 and -2 silencing, HTH01-015 and WZ4003 on matrix plug contraction, proliferation (EdU assay, Ki-67 mRNA), apoptosis and cell death (flowcytometry), viability (CCK-8) and actin organization (phalloidin staining) were examined in cultured WPMY-1 cells. Effects of HTH01-015 and WZ4003 on smooth muscle contraction were assessed in organ bath experirments with human prostate tissues.Results: Effects of silencing were most pronounced on proliferation and cell death, resulting in decreases of proliferation rate by 60% and 70% by silencing of NUAK1 and NUAK2 (compared to scramble siRNA-transfected controls), decreases in Ki-67 by 75% and 77%, while numbers of dead cells after silencing of NUAK1 and NUAK2 amounted to 2.8 and 4.9 fold of scramble-transfected controls. Silencing of each isoform was paralleled by reduced viability, breakdown in actin polymerization, and partial decreases in contractility (maximally 45% by NUAK1 silencing, 58% by NUAK2 silencing). Effects of silencing were mimicked by HTH01-015 and WZ4003, with numbers of dead cells amounting up to 16.1 fold or 7.8 fold with HTH01-015 or WZ4003, compared to solvent-treated controls. Using concentrations of 500 nM, neurogenic contractions of prostate tissues were inhibited partly by HTH01-015 and U46619-induced contractions were inhibited partly by HTH01-015 and WZ4003, while α1-adrenergic and endothelin-1-induced contractions remained unaffected. Using 10 μM, inhibition of endothelin-1-induced contractions by both inhibitors and inhibition of α1-adrenergic contractions by HTH01-015 added to effects seen by 500 nM.Conclusion: NUAK1 and -2 suppress cell death and promote proliferation in prostate stromal cells. A role in stromal hyperplasia appears possible in BPH. Effects of NUAK silencing are mimicked by HTH01-015 and WZ4003.

Sulodexide is a heparinoid compound with wide-ranging pharmacological activities. However, the effect of sulodexide on liver fibrogenesis has not been reported. In this study, we aim to evaluate the therapeutic potential of sulodexide in mouse model of liver fibrosis and explore the underlying antifibrotic mechanisms. We found that sulodexide treatment significantly attenuated thioacetamide (TAA) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver fibrosis in mice. Transcriptome analysis revealed that sulodexide treatment downregulated fibrosis-related genes and liver sinusoidal endothelial cells (LSECs) capillarization-associated genes in fibrotic livers. Immunohistochemistry confirmed that the increased expression of LSEC capillarization-related genes (CD34, CD31 and Laminin) in liver fibrotic tissues was reduced by sulodexide treatment. Scanning electron microscopy showed that LSECs fenestrations were preserved upon sulodexide treatment. Quantitative real-time PCR and immunofluorescence demonstrated that the expression of mesenchymal markers was downregulated by sulodexide administration, suggesting sulodexide inhibited endothelial-mesenchymal transition of LSECs during liver fibrosis. Furthermore, sulodexide administration protected primary LSECs from endothelial dysfunction in vitro. In conclusion, sulodexide attenuated liver fibrosis in mice by restoration of differentiated LSECs, indicating that sulodexide treatment may present as a potential therapy for patients with liver fibrosis.

Abstract Objective Pancreatic body tail carcinoma (PBTC) is a relatively few pancreatic cancer in clinical practice, and its specific clinicopathological features and prognosis have not been fully described. In this study, we aimed to create a nomogram to predict the overall survival (OS) of patients with advanced PBTC. Methods We extracted clinical and related prognostic data of advanced PBTC patients from 2000 to 2018 from the Surveillance, Epidemiology, and End Results database. Independent prognostic factors were selected using univariate and multivariate Cox analyses, and a nomogram was constructed using R software. The C-index, area under the curve (AUC) of receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA) were used to assess the clinical utility of the nomogram. Finally, OS was assessed using the Kaplan–Meier method. Results A total of 1256 patients with advanced PBTC were eventually included in this study. Age, grade, N stage, M stage, surgery, and chemotherapy were identified as independent risk factors using univariate and multivariate Cox regression analyses (p

AIM: To evaluate the cost-utility of iStent inject® with cataract surgery vs cataract surgery alone in patients with mild-to-moderate primary open angle glaucoma (POAG) in the Japanese setting from a public payer's perspective. METHODS: A Markov model was adapted to estimate the cost-utility of iStent inject® plus cataract surgery vs cataract surgery alone in one eye in patients with mild-to-moderate POAG over lifetime horizon from the perspective of Japanese public payer. Japanese sources were used for patients' characteristics, clinical data, utility, and costs whenever available. Non-Japanese data were validated by Japanese clinical experts. RESULTS: In the probabilistic base case analysis, iStent inject® with cataract surgery was found to be cost-effective compared with cataract surgery alone over a lifetime horizon when using the ¥5 000 000/quality-adjusted life year (QALY) willingness-to-pay threshold. The incremental cost-utility ratio (ICUR) was estimated to be ¥1 430 647/QALY gained and the incremental cost-utility ratio (ICER) was estimated to be ¥12 845 154/blind eye avoided. iStent inject® with cataract surgery vs cataract surgery alone was found to increase costs (¥1 025 785 vs ¥933 759, respectively) but was more effective in increasing QALYs (12.80 vs 12.74) and avoiding blinded eyes (0.133 vs 0.141). The differences in costs were mainly driven by costs of primary surgery (¥279 903 vs ¥121 349). In the scenario analysis from a societal perspective, which included caregiver burden, iStent inject® with cataract surgery was found to dominate cataract surgery alone. CONCLUSION: The iStent inject® with cataract surgery is a cost-effective strategy over cataract surgery alone from the public payer's perspective and cost-saving from the societal perspective in patients with mild-to-moderate POAG in Japan.

Abstract Aim Whole transcriptome analysis was conducted to identify differentially expressed RNAs and regulatory networks associated with papillary thyroid carcinoma (PTC). Methods A weighted gene co‐expression network analysis based on high‐throughput sequencing data for six pairs of PTC and adjacent tissue samples was conducted to understand the biological functions and regulatory networks involving long non‐coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs). Results We detected 131, 338, 31, and 556 differentially expressed circRNAs, lncRNAs, miRNAs, and mRNAs, respectively. We identified modules that were significantly positively and negatively related to cancer and lymph node metastasis. Gray and turquoise modules were positively correlated with cancer phenotypes (p

The coal roof of the lower seam of a bifurcated coal seam is always broken and is caused by the mining of the upper seam, which results in difficult support for the coal roof. This seriously affects the safe and efficient mining of the lower seam. Pre-grouting technology is often used to reinforce the regenerated roof in advance to improve its integrity of the roof. In this study, to provide a scientific basis for the layout of surface pre-grouting boreholes, the bifurcated coal seam at the Xutuan coal mine in the Huaibei mining area in China was analyzed. The height and depth of the damage in the coal roof and floor caused by upper seam mining were calculated using theoretical analysis and numerical simulation. The porosity and permeability of the goaf in different positions were calculated by numerical simulation, and the spatial distribution of the porosity and permeability and the slurry diffusion radius of different porosities were determined. Finally, the grouting section and layout of the pre-grouting boreholes were determined. Based on the design scheme, the drilling of the surface boreholes and the addition of the grouting were carried out. The accuracy of the theoretical analysis was verified by field drilling and grouting activity. The research results can provide a basis for the layout of surface pre-grouting boreholes and the selection of the grouting zone in areas of close-distance coal seam mining.

This study aimed to: (1) estimate the disease burden of herpes zoster (HZ) and (2) assess the potential public health impact of introducing adjuvanted recombinant zoster vaccine (RZV) compared with no vaccination in adults aged ≥50 years in Argentina, Brazil, Mexico, Chile, and Colombia using the ZOster ecoNomic Analysis (ZONA) static multicohort Markov model. The model followed individuals aged ≥50 years from administration of RZV over their remaining lifetime. Inputs were based, most often, on local data. First dose coverage was assumed to be 35%, with 75% second dose compliance. It was predicted that without RZV, there would be 23,558,675 HZ cases, 6,115,981 post-herpetic neuralgia (PHN) cases, and 7,058,779 non-PHN complications in the five countries, but introducing RZV under assumed coverage could avoid 4,583,787 (19%) HZ cases, 1,130,751 (18%) PHN cases, and 1,373,419 (19%) non-PHN complications. Also, 10427,504 (20%) doctor’s office visits and 1,630,201 (19%) days of hospitalization could be averted in the three countries (Argentina, Brazil, and Mexico) with available input data. The numbers needed to be vaccinated to avoid one case of HZ were 9–10 across countries, and to avoid one case of PHN, 35–40. One-way sensitivity analyses showed that the input parameters with the largest impact on the estimated number of HZ cases avoided were first dose coverage, initial HZ incidence, and vaccine efficacy waning. In conclusion, the introduction of RZV for older adults in Latin America could greatly reduce the public health burden of HZ and reduce the related doctor visits and hospitalization days.