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Zika virus (ZIKV) infection may lead to severe neurological consequences, including seizures, and early infancy death. However, the involved mechanisms are still largely unknown. TRPC channels play an important role in regulating nervous system excitability and are implicated in seizure development. We investigated whether TRPCs might be involved in the pathogenesis of ZIKV infection. We found that ZIKV infection increases TRPC4 expression in host cells via the interaction between the ZIKV-NS3 protein and CaMKII, enhancing TRPC4-mediated calcium influx. Pharmacological inhibition of CaMKII decreased both pCREB and TRPC4 protein levels, whereas the suppression of either TRPC4 or CaMKII improved the survival rate of ZIKV-infected cells and reduced viral protein production, likely by impeding the replication phase of the viral life cycle. TRPC4 or CaMKII inhibitors also reduced seizures and increased the survival of ZIKV-infected neonatal mice and blocked the spread of ZIKV in brain organoids derived from human-induced pluripotent stem cells. These findings suggest that targeting CaMKII or TRPC4 may offer a promising approach for developing novel anti-ZIKV therapies, capable of preventing ZIKV-associated seizures and death. Synopsis: ZIKV exhibits a high neurotropism and poses significant risks to the developing nervous system. We show that inhibition of the host TRPC4 channel or CaMKII impedes ZIKV propagation in human brain organoids and improves survival in a neonatal mouse model of ZIKV infection. ZIKV upregulates the expression of TRPC4 in host cells through the NS3-CaMKII-CREB pathway. Inhibition of the TRPC4 channel effectively disrupts the replication stage of the ZIKV life cycle. TRPC4 and CaMKII inhibitors successfully block proliferation and spread of ZIKV in human induced pluripotent stem cell (iPSC)-derived brain organoids. Treatment with TRPC4 and CaMKII inhibitors reduces seizures and improves survival rates in newborn mice infected with ZIKV. Thus, targeting TRPC4 holds promise as a potential approach for developing anti-ZIKV drugs, offering new treatment strategies for neurological dysfunction caused by ZIKV virus infection. ZIKV exhibits a high neurotropism and poses significant risks to the developing nervous system. We show that inhibition of the host TRPC4 channel or CaMKII impedes ZIKV propagation in human brain organoids and improves survival in a neonatal mouse model of ZIKV infection. [ABSTRACT FROM AUTHOR]

Golden buckwheat, also called Fagopyrum dibotrys (D. Don) H. Hara, is a plant of the genus Buckwheat in the buckwheat family. The aim of this study was to screen the bioactive ingredients of golden buckwheat extract and investigate the protective effect on acute lung injury (ALI). The ethyl acetate extract (EAE) was identified as the active fraction in LPS‐induced RAW264.7 cells, with gallic acid, proanthocyanidin B2, and epicatechin at 0.0563%, 0.3707%, and 0.3868%, respectively. At the same time, 20 compounds (mainly flavonoids and organic acids) were identified by UPLC‐Q‐Exactive Orbitrap‐HRMS in EAE. Furthermore, the EAE reduced lung histopathology scores in mice with ALI, decreased the dry‐to‐wet weight ratio of lung tissue, and significantly inhibited the concentrations of IL‐1β, TNFα, and IL‐6 in bronchoalveolar lavage fluid (BALF). It also reduced the number of leukocytes, decreased the activity of MPO in lung tissue, and inhibited the levels of TLR4/NLRP3 pathway mRNA and protein in lung tissue. Our study indicated that golden buckwheat as a source of functional food prevents or treats associated lung diseases by modulating the activation of the TLR4/NLRP3 signaling pathway. [ABSTRACT FROM AUTHOR]

In this study, the surface of pyrolysis carbon black (CBp) is modified by integrating the ball milling process with plasma treatment. High‐energy mechanical ball milling enabled more uniform contact and sufficient reaction temperature for the silane coupling agent and CBp. In addition, the impact of plasma activated the ash and surface deposits of CBp, reducing its inertness. Herein, the filler dispersion grade, Payne effect, vulcanization characteristics, and mechanical and dynamic mechanical properties are investigated by considering modified CBp/natural rubber (NR) composites. The ball milling plasma process can reduce the polarity of CBp. Compared with untreated CBp/NR composites, the plasma‐treated SCA‐CBp/NR composites exhibited increased CBp dispersion grades, higher processing safety, better processing fluidity, and improved mechanical properties. The reduced Payne effect ensured more filler‐rubber network structure, resulting in a reduction in rolling resistance. Highlights: The coupling agent and CBp are treated by low‐temperature plasma and ball milling. The process promotes the formation of the filler‐rubber network. The dispersion grade of composites increased by 26.29%. The tensile strength increased by 5.57%, and the rolling resistance decreased by 19.44%. [ABSTRACT FROM AUTHOR]

Differentiation of human embryonic stem cells (hESCs) into human embryonic stem cells‐derived parathyroid‐like cells (hESC‐PT) has clinical significance in providing new therapies for congenital and acquired parathyroid insufficiency conditions. However, a highly reproducible, well‐documented method for parathyroid differentiation remains unavailable. By imitating the natural process of parathyroid embryonic development, we proposed a new hypothesis about the in vitro differentiation of parathyroid‐like cells. Transcriptome, differentiation marker protein detection and parathyroid hormone (PTH) secretion assays were performed after the completion of differentiation. To optimize the differentiation protocol and further improve the differentiation rate, we designed glial cells missing transcription factor 2 (GCM2) overexpression lentivirus transfection assays and constructed hESCs‐derived parathyroid organoids. The new protocol enabled hESCs to differentiate into hESC‐PT. HESC‐PT cells expressed PTH, GCM2 and CaSR proteins, low extracellular calcium culture could stimulate hESC‐PT cells to secrete PTH. hESC‐PT cells overexpressing GCM2 protein secreted PTH earlier than their counterpart hESC‐PT cells. Compared with the two‐dimensional cell culture environment, hESCs‐derived parathyroid organoids secreted more PTH. Both GCM2 lentiviral transfection and three‐dimensional cultures could make hESC‐PT cells functionally close to human parathyroid cells. Our study demonstrated that hESCs could differentiate into hESC‐PT in vitro, which paves the road for applying the technology to treat hypoparathyroidism and introduces new approaches in the field of regenerative medicine. [ABSTRACT FROM AUTHOR]

Boulenophrys sangzhiensis and Boulenophrys tuberogranulata, two narrow‐distributed toad species within the Megophryidae family in southern China, are experiencing population declines due to habitat loss and degradation. Despite their critical conservation status, the two species remain largely overlooked in public and scientific spheres. This study presented the first sequencing, assembly, and annotation of the complete mitogenomes of both species using next‐generation sequencing. The mitogenome of B. sangzhiensis was 16,950 bp, while that of B. tuberogranulata was 16,841 bp, each comprising 13 protein‐coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and a noncoding control region (D‐loop). The gene content, nucleotide composition, and evolutionary rates of each mitogenome were analyzed. Both mitogenomes exhibited negative AT skew and GC skew with high A + T content. ATP8 exhibited the highest evolutionary rate, while COI had the lowest. A phylogenetic analysis based on 28 mitogenomes revealed two major clades of Megophryidae, supporting the classification of two subfamilies, Megophryinae and Leptobrachiinae. Within the subfamily Megophryinae, the genus Boulenophrys was divided into two species groups. Intriguingly, despite coexisting in Zhangjiajie City, B. sangzhiensis and B. tuberogranulata exhibited distinct origins from the two different species groups, underscoring the unique role of the coexisting area Zhangjiajie in driving their speciation and preserving their current populations. A parallel pattern was also identified in the Leptobrachiinae genus Leptobrachium within the same region. This study provided valuable data references and enhanced our understanding of the molecular characteristics of these threatened amphibian species. [ABSTRACT FROM AUTHOR]

Background: Glucagon‐like peptide 1 receptor agonists have been shown to reduce all‐cause and cardiovascular mortality in patients with Type 2 diabetes mellitus (T2DM). The probable increase in heart rate hinders its early usage in acute myocardial infarction patients. In our study, we aimed to find out whether the use of liraglutide in patients with acute myocardial infarction as early as at the time of hospitalization would increase the heart rate. Methods: This was an observational retrospective study. From December 2020 to August 2021, 200 patients with acute myocardial infarction were included in our study and divided into three groups: T2DM + liraglutide group (n = 46), T2DM + non‐liraglutide group (n = 42), and non‐T2DM group (n = 112). The primary outcomes were the differences in heart rate. Secondary outcomes were differences in systolic and diastolic blood pressure. Results: There were no significant differences in heart rate among the three groups at admission, the day before the first shot of liraglutide, and before discharge. There was also no significant difference in heart rate between diabetic patients with acute myocardial infarction and those on liraglutide during the hospital stay. And there were no differences of beta‐blocker dosages among the three groups. Liraglutide did not affect the blood pressure during acute myocardial infarction. Conclusions: Liraglutide did not increase the heart rate in diabetic patients during acute myocardial infarction and did not lead to an increase in the dose of beta‐blockers in the patients. It also had no effect on blood pressure and showed better efficacy in lowering glucose levels without additional hypoglycemic events. [ABSTRACT FROM AUTHOR]

Background: Since the outbreak of COVID‐19, China has undertaken a variety of preventative and control measures, effectively reducing the incidence of numerous infectious diseases among the pediatric population in Hangzhou. We aim to investigate the genetic and epidemiological characteristics of Human parainfluenza virus‐3 (HPIV‐3) in pediatric patients during this period. Methods: A total of 1442 pharyngeal swab samples were collected from outpatients and inpatients with a diagnosis of acute respiratory tract infections (ARTIs) from November 2020 to March 2021. HPIV‐3 was detected by quantitative real time polymerase chain reaction (qRT‐PCR). The L gene of HPIV‐3 positive samples was amplified and sequenced. Results: Among 1442 children with ARTI, the positive rate of HPIV‐3 was 7.07% (102/1442). The positive detection rate was the highest in the 6‐month to 1‐year age group. Coinfection was observed in 36 HPIV‐3‐positive samples (35.29%, 36/102), and adenovirus (ADV) was the most common coinfecting virus (63.89%, 23/36). The L gene of 48 HPIV‐3 positive samples was sequenced. The nucleotide sequence analysis showed high consistency (92.10%–99.40%), and all strains belonged to C3a. Conclusions: During study periods, the positive detection rate of HPIV‐3 among children is high, and the highest proportion of coinfection was observed in HPIV‐3 mixed ADV infection. Phylogenetic analysis revealed that the nucleotide sequence of the L gene of HPIV‐3 was highly consistent, and the main epidemic strain in this area was the C3a subtype. [ABSTRACT FROM AUTHOR]

The use of trastuzumab emtansine (T‐DM1) has revealed significant efficacy in HER2‐positive metastatic breast cancer (MBC). However, optimal therapeutic strategies following T‐DM1 failure remain a subject of debate in clinical practice. In this multicenter, retrospective, real‐world study, we sought to examine the effectiveness and safety of tyrosine kinase inhibitors (TKIs) as a therapeutic strategy in HER2‐positive MBC who developed T‐DM1 resistance. Between September 2018 and December 2022, 66 patients were enrolled. The median progression‐free survival of TKIs‐based therapy was 10.1 months (95% CI, 4.7–15.6). Objective response rate and clinical benefit rate were 18.2 and 66.7%, respectively. TKIs‐based therapy demonstrated better effectiveness in patients who had previously derived benefit from T‐DM1 and featured acquired resistance to trastuzumab. The most common adverse events were diarrhea (36, 54.5%), hand‐foot syndrome (31, 47.0%), and leucopenia (30, 45.5%). In conclusion, TKIs‐based therapy showed promising effectiveness and safety in HER2‐positive MBC patients after T‐DM1 failure. [ABSTRACT FROM AUTHOR]

Enhancing sensitivity to sorafenib can significantly extend the duration of resistance to it, offering substantial benefits for treating patients with hepatocellular carcinoma (HCC). However, the role of ferroptosis in influencing sorafenib sensitivity within HCC remains pivotal. The enhancer of zeste homolog 2 (EZH2) plays a significant role in promoting malignant progression in HCC, yet the relationship between ferroptosis, sorafenib sensitivity, and EZH2 is not entirely clear. Bioinformatic analysis indicates elevated EZH2 expression in HCC, predicting an unfavorable prognosis. Overexpressing EZH2 can drive HCC cell proliferation while simultaneously reducing ferroptosis. Further analysis reveals that EZH2 amplifies the modification of H3K27 me3, thereby influencing TFR2 expression. This results in decreased RNA polymerase II binding within the TFR2 promoter region, leading to reduced TFR2 expression. Knocking down EZH2 amplifies sorafenib sensitivity in HCC cells. In sorafenib‐resistant HepG2(HepG2‐SR) cells, the expression of EZH2 is increased. Moreover, combining tazemetostat—an EZH2 inhibitor—with sorafenib demonstrates significant synergistic ferroptosis‐promoting effects in HepG2‐SR cells. In conclusion, our study illustrates how EZH2 epigenetically regulates TFR2 expression through H3K27 me3, thereby suppressing ferroptosis. The combination of the tazemetostat with sorafenib exhibits superior synergistic effects in anticancer therapy and sensitizes the HepG2‐SR cells to sorafenib, shedding new light on delaying and ameliorating sorafenib resistance. [ABSTRACT FROM AUTHOR]

As a very prospective solid‐state electrolyte, Li10GeP2S12 (LGPS) exhibits high ionic conductivity comparable to liquid electrolytes. However, severe self‐decomposition and Li dendrite propagation of LGPS will be triggered due to the thermodynamic incompatibility with Li metal anode. Herein, by adopting a facile chemical vapor deposition method, an artificial solid electrolyte interphase composed of Li2S is proposed as a single ionic conductor to promote the interface stability of LGPS toward Li. The good electronic insulation coupled with ionic conduction property of Li2S effectively blocks electron transfer from Li to LGPS while enabling smooth passage of Li ions. Meanwhile, the generated Li2S layer remains good interface compatibility with LGPS, which is verified by the stable Li‐plating/stripping operation for over 500 h at 0.15 mA cm−2. Consequently, the all‐solid‐state Li–S batteries (ASSLSBs) with a Li2S layer demonstrate superb capacity retention of 90.8% at 0.2 mA cm−2 after 100 cycles. Even at the harsh condition of 90 °C, the cell can deliver a high reversible capacity of 1318.8 mAh g−1 with decent capacity retention of 88.6% after 100 cycles. This approach offers a new insight for interface modification between LGPS and Li and the realization of ASSLSBs with stable cycle life. [ABSTRACT FROM AUTHOR]

Necrosis in solid tumors is commonly associated with poor prognostic but how these lesions expand remains unclear. Studies have found that neutrophils associate with and contribute to necrosis development in glioblastoma by inducing tumor cell ferroptosis through transferring myeloperoxidase-containing granules. However, the mechanism of neutrophilic granule transfer remains elusive. We performed an unbiased small molecule screen and found that statins inhibit neutrophil-induced tumor cell death by blocking the neutrophilic granule transfer. Further, we identified a novel process wherein neutrophils are engulfed by tumor cells before releasing myeloperoxidase-containing contents into tumor cells. This neutrophil engulfment is initiated by integrin-mediated adhesion, and further mediated by LC3-associated phagocytosis (LAP), which can be blocked by inhibiting the Vps34-UVRAG-RUBCN-containing PI3K complex. Myeloperoxidase inhibition or Vps34 depletion resulted in reduced necrosis formation and prolonged mouse survival in an orthotopic glioblastoma mouse model. Thus, our study unveils a critical role for LAP-mediated neutrophil internalization in facilitating the transfer of neutrophilic granules, which in turn triggers tumor cell death and necrosis expansion. Targeting this process holds promise for improving glioblastoma prognosis. Synopsis: Neutrophils induce ferroptosis in glioblastoma, thus promoting necrosis during early tumor progression but the underlying mechanisms remain unclear. Here, neutrophil engulfment by tumor cells is uncovered as a critical step facilitating the transfer of neutrophilic granules and tumor cell ferroptosis. Statins inhibit neutrophil-induced tumor cell death by blocking neutrophilic granule transfer. Integrin-mediated cell adhesion is required for tumor cell killing by neutrophils. Neutrophils are engulfed by tumor cells before releasing myeloperoxidase-containing contents into tumor cells. LC3-associated phagocytosis is responsible for neutrophil internalization by tumor cells. Myeloperoxidase inhibition or Vps34 depletion reduces necrosis in glioblastomas and prolongs survival of tumor-bearing mice. Neutrophil engulfment by tumor cells facilitates transfer of neutrophilic granules and ferroptosis in brain cancer. [ABSTRACT FROM AUTHOR]

Acid coagulation is the most traditional latex coagulation technology, but this coagulation process leads to delayed vulcanization, corrosiveness, and environmental pollution. Different coagulation processes significantly impact the raw rubber network structure, leading to differences in the properties of both raw rubber and rubber vulcanizates. Raw rubber was prepared by three acid‐free coagulation processes: freeze, microwave, and flash drying. The network density, molecular chain flexibility, molecular weight, processing fluidity, and plasticity retention of the raw rubber were characterized, and the vulcanization characteristics, viscoelasticity, mechanical properties, and dynamic mechanical properties of the cured rubber composites were investigated. Raw rubbers prepared by microwave drying and flash drying had higher crosslink density, more flexible molecular chains, larger molecular weight, and wider molecular weight distribution, thereby increasing the crosslink density of rubber vulcanizates. The crosslink density of the raw rubber prepared by microwave drying versus the acid coagulated raw rubber increased by 51% to 105.71 mol/m3, the tensile strength increased by 16% to reach 28.12 MPa, and the elastic modulus and rolling resistance under dynamic stress increased. This paper provides a new idea for analyzing the relationship between the raw rubber network structure and the properties of vulcanized rubber. Highlights: Acid‐free raw rubbers are prepared by freeze, microwave, and flash drying.Coagulation processes significantly impact the raw rubber network structures.Effects of raw rubber network structures on properties are investigated.Crosslink density, plasticity retention, and tensile strength are improved. [ABSTRACT FROM AUTHOR]

This article discusses a study published in Cell Proliferation that investigates the changes in mRNA isoforms during zygotic genome activation (ZGA) in mice. ZGA is the first transcriptional event after fertilization and involves the degradation of maternal mRNA and the transcription of new mRNAs from the zygotic genome. The study compares the transcriptomes of embryos with different parental genomes and stages of development to identify differential alternative splicing and alternative promoter usage events. The findings suggest that there are specific patterns of mRNA isoforms generated from the paternal and maternal genomes during ZGA, providing insights into how sperm and oocyte genomes regulate mammalian development. The study also examines the differences in mRNA isoforms before and after ZGA in mice and humans, identifying changes that can have functional implications beyond differences in mRNA abundance. The study provides insights into the regulatory mechanisms involved in early embryonic development and suggests that isoform changes can serve as markers for ZGA events, although further validation is needed to understand the specific functions of each isoform. The study was supported by various funding sources and the authors declare no conflicts of interest. [Extracted from the article]

The fast recombination of photogenerated electrons and holes remains a major issue in hindering photocatalytic efficiency. Apart from traditional methods, such as rare metal deposition and element doping, the introduction of a built‐in electric field has been proven an efficient way in recent years. Ferroelectrics, which possess spontaneous polarization and associated polarization electric fields, are attracting more attention as photocatalysts. In this study, Bi2MoO6 spheres with different hierarchical upper nanostructures are synthesized through a one‐pot hydrothermal method. With this porous structure and the intrinsic ferroelectricity, BMO spheres present excellent physisorption and photodegradation ability toward dye molecules. After corona poling treatment, the ferroelectric field of the BMO samples was enhanced, and the recombination of charges was suppressed, leading to an obvious increase in photocatalytic rate. The origin BMO‐5 can reach a total degradation of RhB in 20 min, and the polarized BMO‐5 (BMO‐5P) can remove all RhB molecules instantly through the physisorption process. Apart from BMO‐5, other samples also present excellent catalytic behavior. Origin BMO‐2 can fully degrade the RhB in 40 min, and the degradation time of polarized BMO‐2P is 30 min. The hierarchical structure and internal polarized electric field endow BMO spheres with outstanding adsorption purification and photodegradation ability and provide a new comprehensive strategy for the catalyst design. [ABSTRACT FROM AUTHOR]

Deep coal‐rock formations are subjected to complex stress environments characterized by high static stresses and dynamic disturbances. To study the damage, fracture, and energy evolution characteristics of coal‐rock under dynamic–static combined loading, a new multiscale constitutive model for coal‐rock under dynamic–static combined loading is proposed based on micromechanics, and it is implemented into the LS‐DYNA solver. A numerical model of coal‐rock Split Hopkinson Pressure Bar under dynamic–static combined loading is established using LS‐DYNA, and research on the mechanical and energy evolution characteristics of coal‐rock under one‐dimensional and three‐dimensional dynamic–static combined loading is conducted. The results show that under one‐dimensional dynamic–static combined loading, with the increase of precompression, the dynamic peak stress linearly decreases while the combined peak stress linearly increases, and the dissipated energy of the specimen shows a decreasing trend. The fracture patterns of the coal‐rock specimen include internal shear fracture and external tensile fracture, and eventually, these two modes of fracture intersect to form macroscopic mesh cracks. As the axial pressure increases, the degree of specimen fragmentation gradually increases. Under three‐dimensional dynamic–static combined loading, with the increase of preconfining pressure, the stress–strain curve of the specimen will transition from “stress drop” to “stress rebound” after the peak. The peak stress increases with the increase of confining pressure, and the energy dissipation density of the specimen increases first and then decreases with the increase of confining pressure. With the increase of confining pressure, the hoop deformation of the specimen plays a constraining role, and the degree of specimen fracture gradually weakens, and the time of fracture occurrence gradually delays. The research results contribute to revealing the mechanical and energy mechanisms of rockburst disasters in deep coal mines. [ABSTRACT FROM AUTHOR]

Summary: Calcium ion (Ca2+) serves as a versatile and conserved second messenger in orchestrating immune responses. In plants, plasma membrane‐localized Ca2+‐permeable channels can be activated to induce Ca2+ influx from extracellular space to cytosol upon pathogen infection. Notably, different immune elicitors can induce dynamic Ca2+ signatures in the cytosol. During pattern‐triggered immunity, there is a rapid and transient increase in cytosolic Ca2+, whereas in effector‐triggered immunity, the elevation of cytosolic Ca2+ is strong and sustained. Numerous Ca2+ sensors are localized in the cytosol or different intracellular organelles, which are responsible for detecting and converting Ca2+ signals. In fact, Ca2+ signaling coordinated by cytosol and subcellular compartments plays a crucial role in activating plant immune responses. However, the complete Ca2+ signaling network in plant cells is still largely ambiguous. This review offers a comprehensive insight into the collaborative role of intracellular Ca2+ stores in shaping the Ca2+ signaling network during plant immunity, and several intriguing questions for future research are highlighted. [ABSTRACT FROM AUTHOR]

Messenger RNA (mRNA) cancer vaccines are a new class of immunotherapies that can activate the immune system to recognize and destroy cancer cells. However, their effectiveness in treating colorectal cancer located on the mucosal surface of the gut is limited due to the insufficient activation of mucosal immune response and inadequate infiltration of cytotoxic T cells into tumors. To address this issue, a new mRNA cancer vaccine is developed that can stimulate mucosal immune responses in the gut by co‐delivering all‐trans‐retinoic acid (ATRA) and mRNA using lipid nanoparticle (LNP). The incorporation of ATRA has not only improved the mRNA transfection efficiency of LNP but also induced high expression of gut‐homing receptors on vaccine‐activated T cells. Additionally, the use of LNP improves the aqueous solubility of ATRA, eliminating the need for toxic solvents to administer ATRA. Upon intramuscular injections, ATRA‐adjuvanted mRNA‐LNP significantly increase the infiltration of antigen‐specific, cytotoxic T cells in the lamina propria of the intestine, mesenteric lymph nodes, and orthotopic colorectal tumors, resulting in significantly improved tumor inhibition and prolonged animal survival compared to conventional mRNA‐LNP without ATRA. Overall, this study provides a promising approach for improving the therapeutic efficacy of mRNA cancer vaccines against colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Tall wheatgrass is a perennial salt‐tolerant bunchgrass, which is a promising candidate for establishing a "Coastal Grass Belt" in China, particularly in the coastal saline–alkaline soils surrounding the Bohai Sea. Methods: Seven harvesting treatments were performed to explore the optimal harvesting time and frequency for tall wheatgrass in coastal area. The dry matter yield (DMY) and forage nutritional values were investigated for each cut. The correlation between harvesting time and frequency thereof among the investigated traits was also determined. Results: The results showed that the two‐cut on June 18 and October 29 produced the highest DMY. Another two‐cut on May 26 and October 29 produced a relatively high crude protein (CP) yield. The DMY, contents of neutral detergent fiber (NDF), acid detergent fiber (ADF), and crude cellulose (CC) as well as CP yield were positively correlated to plant height, while the CP content and the relative feed value (RFV) were negatively correlated to plant height. The accumulating growing degree days, accumulated precipitation, and sunshine duration were positively correlated with plant height, DMY, contents of NDF, ADF, and CC as well as CP yield, but negatively correlated with CP content and RFV for the first cut. Conclusions: The two‐cut treatment at the end of May and October may be suitable for tall wheatgrass in the "Coastal Grass Belt" targeted area. [ABSTRACT FROM AUTHOR]

Summary: Grain size is a crucial agronomic trait that affects stable yield, appearance, milling quality, and domestication in rice. However, the molecular and genetic relationships among QTL genes (QTGs) underlying natural variation for grain size remain elusive.Here, we identified a novel QTG SGW5 (suppressor of gw5) by map‐based cloning using an F2 segregation population by fixing same genotype of the master QTG GW5. SGW5 positively regulates grain width by influencing cell division and cell size in spikelet hulls. Two nearly isogenic lines exhibited a significant differential expression of SGW5 and a 12.2% increase in grain yield. Introducing the higher expression allele into the genetic background containing the lower expression allele resulted in increased grain width, while its knockout resulted in shorter grain hulls and dwarf plants.Moreover, a cis‐element variation in the SGW5 promoter influenced its differential binding affinity for the WRKY53 transcription factor, causing the differential SGW5 expression, which ultimately leads to grain size variation. GW5 physically and genetically interacts with WRKY53 to suppress the expression of SGW5.These findings elucidated a new pathway for grain size regulation by the GW5‐WRKY53‐SGW5 module and provided a novel case for generally uncovering QTG interactions underlying the genetic diversity of an important trait in crops. [ABSTRACT FROM AUTHOR]

Human enterovirus A71 (EV‐A71) is a significant etiological agent responsible for epidemics of hand, foot, and mouth disease (HFMD) in Asia‐Pacific regions. There are presently no licensed antivirals against EV‐A71, and the druggable target for EV‐A71 remains very limited. The phenotypic hit 10,10′‐bis(trifluoromethyl) marinopyrrole A derivative, herein termed MPA‐CF3, is a novel potent small‐molecule inhibitor against EV‐A71, but its pharmacological target(s) and antiviral mechanisms are not defined. Here, quantitative chemoproteomics deciphered the antiviral target of MAP‐CF3 as host factor coatomer subunit zeta‐1 (COPZ1). Mechanistically, MPA‐CF3 disrupts the interaction of COPZ1 with the EV‐A71 nonstructural protein 2C by destabilizing COPZ1 upon binding. The destruction of this interaction blocks the coatomer‐mediated transport of 2C to endoplasmic reticulum, and ultimately inhibits EV‐A71 replication. Taken together, our study disclosed that MPA‐CF3 can be a structurally novel host‐targeting anti‐EV‐A71 agent, providing a structural basis for developing the COPZ1‐targeting broad‐spectrum antivirals against enteroviruses. The mechanistic elucidation of MPA‐CF3 against EV‐A71 may offer an alternative COPZ1‐involved therapeutic pathway for enterovirus infection. [ABSTRACT FROM AUTHOR]

Chloroplasts play a vital role in plant growth and development, which are the main sites of photosynthesis and the production of hormones and metabolites. Despite their significance, the regulatory mechanisms governing chloroplast development remain unclear. In our investigation, we identified a rice mutant with defective chloroplasts in rice (Oryza sativa L.), named albino lethal 13 (osal13), which displayed a distinct albino phenotype in leaves, ultimately resulting in seedling lethality. Molecular cloning revealed that OsAL13 encodes a novel rice protein with no homologous gene or known conserved domain. This gene was located in the chloroplast and exhibited constitutive expression in various tissues, particularly in green tissues and regions of active cell growth. Our study's findings reveal that RNAi‐mediated knockdown of OsAL13 led to a pronounced albino phenotype, reduced chlorophyll and carotenoid contents, a vesicle chloroplast structure, and a decrease in the expression of chloroplast‐associated genes. Consequently, the pollen fertility and seed setting rate were lower compared with the wild type. In contrast, the overexpression of OsAL13 resulted in an increased photosynthetic rate, a higher total grain number per panicle, and enhanced levels of indole‐3‐acetic acid (IAA) in the roots and gibberellin A3 (GA3) in the shoot. These outcomes provide new insights on the role of OsAL13 in regulating chloroplast development in rice. [ABSTRACT FROM AUTHOR]

Pore‐throat structure is a key factor that influences the storage and fluid flow capacity of tight sandstone reservoirs. Taking the tight sandstone reservoir of Xu2 Fm in Zhongba area as an example, the reservoir quality, pore‐throat type and pore size distribution of tight sandstone in the study area were described by casting thin section, scanning electron microscope and high‐pressure mercury injection test. In order to quantitatively characterize the complexity and heterogeneity of pore‐throat structure, fractal analysis was performed using mercury saturation and pore size data. This study mainly reveals the relationship between the geometric shape characteristics and fractal dimension of the binary pore structure of ultra‐low permeability tight sandstone and clarifies the influence of different scale pore throats on reservoir physical properties. The results indicate that the physical properties of the reservoir in the study area are poor, the pores are mainly intergranular pores and dissolution pores, the throat is flake and necked and the pore size distribution range is large. The fractal curve obtained by the mercury saturation method shows a significant turning point, and the pore‐throat system is divided into two types: small‐scale and large‐scale. The fractal dimension of large‐scale pore throat is greater than the three‐dimensional Euclidean space dimension, which does not conform to the fractal theory. The fractal dimension of small‐scale pore throat is closely related to the pore‐throat structure and has obvious fractal characteristics. The geometric shape of binary pore‐throat structure in tight sandstone is the main factor affecting the difference of fractal dimension. The development of small pores in sandstone is positively correlated with the total porosity, but its contribution to permeability is relatively low. The physical properties of tight sandstone are mainly controlled by the development degree of large‐scale pore throat. [ABSTRACT FROM AUTHOR]

The triple‐network model has been widely applied in neuropsychiatric disorders including autism spectrum disorder (ASD). However, the mechanism of causal regulations within the triple‐network and their relations with symptoms of ASD remains unclear. 81 male ASD and 80 well matched typically developing control (TDC) were included in this study, recruited from Autism Brain Image Data Exchange‐I datasets. Spatial reference‐based independent component analysis was used to identify the anterior and posterior part of default‐mode network (aDMN and pDMN), salience network (SN), and bilateral executive‐control network (ECN) from resting‐state functional magnetic resonance imaging data. Spectral dynamic causal model and parametric empirical Bayes with Bayesian model reduction/average were adopted to explore the effective connectivity (EC) within triple‐network and the relationship between EC and autism diagnostic observation schedule (ADOS) scores. After adjusting for age and site effect, ASD and TDC groups both showed inhibition patterns. Compared with TDC, ASD group showed weaker self‐inhibition in aDMN and pDMN, stronger inhibition in pDMN→aDMN, weaker inhibition in aDMN→LECN, pDMN→SN, LECN→SN, and LECN→RECN. Furthermore, negative relationships between ADOS scores and pDMN self‐inhibition strength, as well as with the EC of pDMN→aDMN were observed in ASD group. The present study reveals imbalanced effective connections within triple‐networks in ASD children. More attentions should be focused at the pDMN, which modulates the core symptoms of ASD and may serve as an important region for ASD diagnosis and the target region for ASD treatments. [ABSTRACT FROM AUTHOR]

As the global data strategy deepens and data elements accelerate integrating and flowing more rapidly, the demand for data security and privacy protection has become increasingly prominent. Confidential computing emerges as a crucial security technology to solve security and privacy problem, and it is also a hot subject of in contemporary security technologies. Leveraging collaborative security in both hardware and software, it builds a trusted execution environment to ensure confidentiality and integrity protection for data in use. This paper provides a comprehensive overview of the development process of confidential computing, summarizing its current research status and issues, which focuses on the security requirements for data security and privacy protection. Furthermore, it deeply analyses the common technical features of confidential computing, and proposes a trusted confidential computing architecture based on collaborative hardware and software trust. Then, it elaborates on the research status and issues of confidential computing from four aspects: hardware security, architecture and key technologies, applications, and standards and evaluation. Finally, this paper provides a synthesis and outlook for the future development of confidential computing. In summary, confidential computing is currently in a rapidly developing stage and will play an important role in cyber security in the future. [ABSTRACT FROM AUTHOR]

CRISPR‐based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9 and Cas12a restricts their efficient delivery by the adeno‐associated virus (AAV) for in vivo gene editing. Being exceptionally small, the recently engineered type V‐F CRISPR‐Cas12f1 systems can overcome the cargo packaging bottleneck and present as strong candidates for therapeutic applications. In this study, the pairwise editing efficiencies of different engineered Cas12f1/sgRNA scaffold combinations are systemically screened and optimized, and the CasMINI_v3.1/ge4.1 system is identified as being able to significantly boost the gene editing activity. Moreover, packaged into single AAV vectors and delivered via subretinal injection, CasMINI_v3.1/ge4.1 achieves remarkably high in vivo editing efficiencies, over 70% in transduced retinal cells. Further, the efficacy of this Cas12f1 system‐based gene therapy to treat retinitis pigmentosa in RhoP23H mice is demonstrated by the therapeutic benefits achieved including rescued visual function and structural preservation. And minimal bystander editing activity is detected. This work advances and expands the therapeutic potential of the miniature Cas12f1 system to support efficient and accurate in vivo gene therapy. [ABSTRACT FROM AUTHOR]

Secondary trastuzumab resistance represents an evolutionary adaptation of HER2‐positive breast cancer during anti‐HER2 treatment. Most current studies have tended to prioritize HER2 and its associated signaling pathways, often overlooking broader but seemingly less relevant cellular processes, along with their associated genetic and epigenetic mechanisms. Here, transcriptome data is not only characterized but also examined epigenomic and 3D genome architecture information in both trastuzumab‐sensitive and secondary‐resistant breast cancer cells. The findings reveal that the global metabolic reprogramming associated with trastuzumab resistance may stem from genome‐wide alterations in both histone modifications and chromatin structure. Specifically, the transcriptional activities of key genes involved in lipid metabolism appear to be regulated by variant promoter H3K27me3 and H3K4me3 modifications, as well as promoter‐enhancer interactions. These discoveries offer valuable insights into how cancer cells adapt to anti‐tumor drugs and have the potential to impact future diagnostic and treatment strategies. [ABSTRACT FROM AUTHOR]

Introduction: Intrahepatic cholangiocarcinoma (ICC) is characterized by a dismal prognosis with limited therapeutic alternatives. To explore phosphatase and tension homolog (PTEN) as a biomarker for proteasome inhibition in ICC, we conducted a phase II trial to assess the second‐line efficacy of bortezomib in PTEN‐deficient advanced ICC patients. Methods: A total of 130 patients with advanced ICC in our centre were screened by PTEN immunohistochemical staining between 1 July 2017, and 31 December 2021, and 16 patients were ultimately enrolled and treated with single‐agent bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21‐day cycle. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1. Results: The median follow‐up was 6.55 months (95% confidence interval [CI]: 0.7–19.9 months). Among the 16 enrolled patients, the ORR was 18.75% (3/16) and the disease control rate was 43.75% (7/16). The median progress‐free survival was 2.95 months (95% CI: 2.1–5.1 months) and the median overall survival (mOS) was 7.2 months (95% CI: 0.7–21.6 months) in the intent‐to‐treat‐patients. Treatment‐related adverse events of any grade were reported in 16 patients, with thrombopenia being the most common toxicity. Patients with PTEN staining scores of 0 were more likely to benefit from bortezomib than those with staining scores > 0. Conclusions: Bortezomib yielded an encouraging objective response and a favourable OS as a second‐line agent in PTEN‐deficient ICC patients. Our findings suggest bortezomib as a promising therapeutic option for patients with PTEN‐deficient ICC. Highlights: There is a limited strategy for the second‐line option of intrahepatic cholangiocarcinoma (ICC).This investigator‐initiated phase 2 study evaluated bortezomib in ICC patients with phosphatase and tension homology deficiency.The overall response rate was 18.75% and the overall survival was 7.2 months in the intent‐to‐treat cohort.These results justify further developing bortezomib in ICC patients with PTEN deficiency. [ABSTRACT FROM AUTHOR]

Predators significantly impact the development process and subsequently influence the metamorphic decisions of amphibian larvae. Larvae often exhibit induced growth and metamorphic plasticity in response to the presence of predators. However, growth and development rates are not always perfectly correlated, growth responses can vary throughout ontogeny. It is crucial to consider the stage‐specific growth responses induced by predators. Here, we employ a critical windows experimental design and examine development‐related growth and metamorphic responses to predators in the endangered Chinhai spiny newt (Echinotriton chinhaiensis). Our findings reveal that predators constrain the development process of spiny newt larvae and also impact survival to metamorphosis. Inducible plasticity predominantly exhibits in the early and middle stages of larval development. Our results also suggest that diverse developmental plasticity has been adopted by larvae in response to predators. The presence of predators during early stage induces larvae to exhibit a same size at metamorphosis but a prolonged time to metamorphosis, while predators present during middle stage induce larvae to exhibit a large size at metamorphosis but a same time to metamorphosis. The presence of predators at the late developmental stage does not induce any plasticity in larval growth and metamorphosis. Moreover, these results also suggest that several stages of larval development are likely critical developmental windows for spiny newt larvae. This study not only provides basic biological information on predator‐induced developmental plasticity of the endangered Chinhai spiny newt but also likely provides biological insights for the implementation of in situ conservation and preservation efforts for endangered species. [ABSTRACT FROM AUTHOR]

Neurotrophic receptor tyrosine kinase 3 (NTRK3) has pleiotropic functions: it acts not only as an oncogene in breast and gastric cancers but also as a dependence receptor in tumor suppressor genes in colon cancer and neuroblastomas. However, the role of NTRK3 in upper tract urothelial carcinoma (UTUC) is not well documented. This study investigated the association between NTRK3 expression and outcomes in UTUC patients and validated the results in tests on UTUC cell lines. A total of 118 UTUC cancer tissue samples were examined to evaluate the expression of NTRK3. Survival curves were generated using Kaplan–Meier estimates, and Cox regression models were used for investigating survival outcomes. Higher NTRK3 expression was correlated with worse progression‐free survival, cancer‐specific survival, and overall survival. Moreover, the results of an Ingenuity Pathway Analysis suggested that NTRK3 may interact with the PI3K‐AKT‐mTOR signaling pathway to promote cancer. NTRK3 downregulation in BFTC909 cells through shRNA reduced cellular migration, invasion, and activity in the AKT‐mTOR pathway. Furthermore, the overexpression of NTRK3 in UM‐UC‐14 cells promoted AKT‐mTOR pathway activity, cellular migration, and cell invasion. From these observations, we concluded that NTRK3 may contribute to aggressive behaviors in UTUC by facilitating cell migration and invasion through its interaction with the AKT‐mTOR pathway and the expression of NTRK3 is a potential predictor of clinical outcomes in cases of UTUC. [ABSTRACT FROM AUTHOR]

Summary: Rutin, a flavonoid rich in buckwheat, is important for human health and plant resistance to external stresses. The hydrolysis of rutin to quercetin underlies the bitter taste of Tartary buckwheat. In order to identify rutin hydrolysis genes, a 200 genotypes mini‐core Tartary buckwheat germplasm resource was re‐sequenced with 30‐fold coverage depth. By combining the content of the intermediate metabolites of rutin metabolism with genome resequencing data, metabolite genome‐wide association analyses (GWAS) eventually identified a glycosyl hydrolase gene FtGH1, which could hydrolyse rutin to quercetin. This function was validated both in Tartary buckwheat overexpression hairy roots and in vitro enzyme activity assays. Mutation of the two key active sites, which were determined by molecular docking and experimentally verified via overexpression in hairy roots and transient expression in tobacco leaves, exhibited abnormal subcellular localization, suggesting functional changes. Sequence analysis revealed that mutation of the FtGH1 promoter in accessions of two haplotypes might be necessary for enzymatic activity. Co‐expression analysis and GWAS revealed that FtbHLH165 not only repressed FtGH1 expression, but also increased seed length. This work reveals a potential mechanism behind rutin metabolism, which should provide both theoretical support in the study of flavonoid metabolism and in the molecular breeding of Tartary buckwheat. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to illuminate the neuropathological landscape of attention deficit hyperactivity disorder (ADHD) by a multiscale macro–micro‐molecular perspective from in vivo neuroimaging data. Methods: The "ADHD‐200 initiative" repository provided multi‐site high‐quality resting‐state functional connectivity (rsfc‐) neuroimaging for ADHD children and matched typically developing (TD) cohort. Diffusion mapping embedding model to derive the functional connectome gradient detecting biologically plausible neural pattern was built, and the multivariate partial least square method to uncover the enrichment of neurotransmitomic, cellular and chromosomal gradient‐transcriptional signatures of AHBA enrichment and meta‐analytic decoding. Results: Compared to TD, ADHD children presented connectopic cortical gradient perturbations in almost all the cognition‐involved brain macroscale networks (all pBH <0.001), but not in the brain global topology. As an intermediate phenotypic variant, such gradient perturbation was spatially enriched into distributions of GABAA/BZ and 5‐HT2A receptors (all pBH <0.01) and co‐varied with genetic transcriptional expressions (e.g. DYDC2, ATOH7, all pBH <0.01), associated with phenotypic variants in episodic memory and emotional regulations. Enrichment models demonstrated such gradient‐transcriptional variants indicated the risk of both cell‐specific and chromosome‐ dysfunctions, especially in enriched expression of oligodendrocyte precursors and endothelial cells (all pperm <0.05) as well enrichment into chromosome 18, 19 and X (pperm <0.05). Conclusions: Our findings bridged brain macroscale neuropathological patterns to microscale/cellular biological architectures for ADHD children, demonstrating the neurobiologically pathological mechanism of ADHD into the genetic and molecular variants in GABA and 5‐HT systems as well brain‐derived enrichment of specific cellular/chromosomal expressions. [ABSTRACT FROM AUTHOR]

The evolution of Artificial Intelligence of Things (AIoT) pushes connectivity from human‐to‐things and things‐to‐things, to AI‐to‐things, has resulted in more complex physical networks and logical associations. This has driven the demand for Internet of Things (IoT) devices with powerful edge data processing capabilities, leading to exponential growth in device quantity and data generation. However, conventional data preprocessing methods, such as data compression and encoding, often require edge devices to allocate computational resources for decoding. Additionally, some lossy compression methods, like JPEG, may result in the loss of important information, which has negative impact on the AI training. To address these challenges, this paper proposes a two‐step attribute reduction approach, targeting devices and dimensions, to reduce the massive amount of data in the AIoT network while avoiding unnecessary utilization of edge device resources for decoding. The device‐oriented and dimension‐oriented attribute reductions identify important devices and dimensions, respectively, to mitigate the multimodal interference caused by the large‐scale devices in the AIoT network and the curse of dimensionality associated with high‐dimensional AIoT data. Numerical results and analysis show that this approach effectively eliminates redundant devices and numerous dimensions in the AIoT network while maintaining the basic data correlation. [ABSTRACT FROM AUTHOR]

Previously a ring finger protein 20 (RNF20) is found to be essential for meiotic recombination and mediates H2B ubiquitination during spermatogenesis. However, its role in meiotic division is still unknown. Here, it is shown that RNF20 is localized at both centromeres and spindle poles, and it is required for oocyte acentrosomal spindle organization and female fertility. RNF20‐depleted oocytes exhibit severely abnormal spindle and chromosome misalignment caused by defective bipolar organization. Notably, it is found that the function of RNF20 in spindle assembly is not dependent on its E3 ligase activity. Instead, RNF20 regulates spindle assembly by recruiting tropomyosin3 (TPM3) to both centromeres and spindle poles with its coiled‐coil motif. The RNF20‐TPM3 interaction is essential for acentrosomal meiotic spindle assembly. Together, the studies uncover a novel function for RNF20 in mediating TPM3 recruitment to both centromeres and spindle poles during oocyte spindle assembly. [ABSTRACT FROM AUTHOR]

The North Qinling Orogenic Belt (NQB) records the pivotal geological information for understanding the Palaeozoic evolution of the Qinling Orogenic Belt (QOB). Previous studies mainly focused on the subduction–collision process along the Shangdan suture zone before the Early Devonian. However, as the significant interim period between the Early Palaeozoic and Mesozoic orogeny, the Late Palaeozoic tectonic evolution of the NQB remains poorly understood. Fortunately, the Carboniferous magmatic rocks discovered this time provide substantial geological evidence for revealing the Late Palaeozoic tectonic history of the Qinling Orogenic Belt. This paper will provide a detailed analysis of zircon U–Pb ages, geochemical characteristics and Sr‐Nd‐Hf isotopic compositions of Carboniferous rocks. The Carboniferous magmatic rocks are categorized as highly differentiated S‐type granite and monzodiorite, formed at 350 ± 2.4 Ma and 353 ± 5.2 Ma, respectively. The granite shows weak peraluminous (A/CNK = 1.02–1.11) and shoshonite nature. Based on the isotopic composition and trace element characteristics, we propose that the Qinling Group paragneiss is the primary source of the Carboniferous granite. Monzodiorite is characterized by enriched LREEs and LILEs (Ba, K and Pb), depleted HFSEs (Th, Nb, Ta and Ti) and enriched Sr‐Nd isotopic composition. Monzodiorite magma source region consists of continental crustal material and lithospheric metasomatized mantle. Carboniferous magmatic rocks are the product of an extensional tectonic setting, which indicates the NQB tectonic regimes transition from compression to extension during the Carboniferous. [ABSTRACT FROM AUTHOR]

Background: Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post‐injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non‐neuronal markers or pan‐neuronal markers with constitutive expressions. Methods: In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA‐sequencing and qRT‐PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme‐linked immune‐sorbent assay (ELISA) kits. Results: Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function. Conclusions: ATF3 is an easily measurable, neuron‐specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties. Highlights: ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively.Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke.ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke. [ABSTRACT FROM AUTHOR]

High metastatic propensity of osteosarcoma leads to its therapeutic failure and poor prognosis. Although nuclear activation miRNAs (NamiRNAs) are reported to activate gene transcription via targeting enhancer and further promote tumor metastasis, it remains uncertain whether NamiRNAs regulate osteosarcoma metastasis and their exact mechanism. Here, we found that extracellular vesicles of the malignant osteosarcoma cells (143B) remarkably increased the migratory abilities of MNNG cells representing the benign osteosarcoma cells by two folds, which attributed to their high miR‐1246 levels. Specially, miR‐1246 located in nucleus could activate the migration gene expression (such as MMP1) to accelerate MNNG cell migration through elevating the enhancer activities via increasing H3K27ac enrichment. Instead, MMP1 expression was dramatically inhibited after Argonaute 2 (AGO2) knockdown. Notably, in vitro assays demonstrated that AGO2 recognized the hybrids of miR‐1246 and its enhancer DNA via PAZ domains to prevent their degradation from RNase H and these protective roles of AGO2 may favor the gene activation by miR‐1246 in vivo. Collectively, our findings suggest that miR‐1246 could facilitate osteosarcoma metastasis through interacting with enhancer to activate gene expression dependent on AGO2, highlighting the nuclear AGO2 as a guardian for NamiRNA‐targeted gene activation and the potential of miR‐1246 for osteosarcoma metastasis therapy. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) are widely used in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC); however, the toxicity profiles are inconclusive. Methods: Clinical trials evaluating ICIs for R/M HNSCC were searched from online databases. The characteristics of the studies and the results of incidences of any grade treatment‐related adverse events (trAEs), grade three or more trAEs, treatment‐related deaths, trAEs leading to discontinuation of treatment, and specific trAEs were extracted. Results: Twenty studies with 3756 patients were included. The pooled incidences of any grade trAEs, grade three or more trAEs, treatment‐related deaths, trAEs leading to discontinuation of treatment for overall population were 62.07% (95% CI, 59.07%–65.02%), 13.82% (95% CI, 11.23%–16.62%), 0.39% (95% CI, 0.15%–0.71%), 3.99% (95% CI, 2.36%–5.95%), respectively. Programmed cell death protein 1 (PD‐1) inhibitors monotherapy and ICIs combination therapy had significantly higher incidences of any grade trAEs (odds ratio [OR], 1.25, 95% CI, 1.05–1.49 and 1.36, 95% CI, 1.15–1.60, respectively), grade three or more trAEs (OR, 1.41, 95% CI, 1.08–1.84 and 1.79, 95% CI, 1.39–2.30, respectively), trAEs leading to discontinuation of treatment (OR, 3.98, 95% CI, 2.06–7.70 and 10.14, 95% CI, 5.49–18.70, respectively) compared with programmed death‐ligand 1 (PD‐L1) inhibitors monotherapy. ICIs combination therapy had a significantly higher incidence of grade three or more trAEs compared with PD‐1 inhibitors monotherapy (OR, 1.27, 95% CI, 1.03–1.55); however, the incidences of any grade trAEs and trAEs leading to discontinuation of treatment were not significant different. Conclusions: Our study suggests that the incidences of grade three or more trAEs, treatment‐related deaths, and trAEs leading to discontinuation of treatment are low in R/M HNSCC patients treated with ICIs. PD‐L1 inhibitors monotherapy may be safer compared with PD‐1 inhibitors monotherapy and ICIs combination therapy. [ABSTRACT FROM AUTHOR]

Herein, a meta‐analysis was conducted to systematically evaluate the effect of humanised care on maternal postoperative wound infections in patients who underwent caesarean section. A computerised search of Embase, Cochrane Library, PubMed, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database and Wanfang database was performed, supplemented by a manual search from database inception to September 2023, to collate randomised controlled trials (RCTs) regarding the application of humanised care during the perioperative period of caesarean section. Two researchers screened and selected studies identified according to inclusion and exclusion criteria, and the included literature was evaluated for quality, extracted information and required data. Data analysis was performed using RevMan 5.4 software. Twenty RCTs comprising 2408 patients were included. The results revealed the humanised care group had a lower incidence of postoperative wound infections (0.83% vs. 4.32%, odds ratio [OR]: 0.26, 95% confidence interval [CI]: 0.15–0.46, p < 0.00001) and fewer postoperative complications than the conventional care group (4.32% vs. 16.35%, OR: 0.23, 95% CI: 0.16–0.31, p < 0.00001), with lower anxiety scores (standardised mean difference [SMD]: −3.15, 95% CI: −3.90 to −2.40, p < 0.00001) and depression scores (SMD: −3.68, 95% CI: −4.49 to −2.88, p < 0.00001). The application of humanised care during the perioperative period of caesarean section can prevent postoperative wound infection, reduce postoperative complications and help alleviate maternal anxiety and depression, which is worthy of clinical promotion and application. [ABSTRACT FROM AUTHOR]

Atherosclerosis, a chronic inflammatory disease of aorta, remains the major cause of morbidity and mortality among cardiovascular disease patients. Macrophage foam cell formation and inflammation are critically involved in early stages of atherosclerosis, hence chemopreventive targeting of foam cell formation by nutraceuticals may be a promising approach to curbing the progression of atherosclerosis. However, many nutraceuticals including berberine and ginkgetin have low stability, tissue/cell penetration and bioavailability resulting in inadequate chemotherapeutic effects of these nutraceuticals. We have used avocado‐derived extracellular vesicles (EV) isolated from avocado (EVAvo) as a novel carrier of nutraceuticals, in a strategy to alleviate the build‐up of macrophage foam cells and expression of inflammatory genes. Our key findings are: (i) Avocado is a natural source of plant‐derived EVs as shown by the results from transmission electron microscopy, dynamic light scattering and NanoBrook Omni analysis and atomic force microscopy; (ii) EVAvo are taken up by macrophages, a critical cell type in atherosclerosis; (iii) EVAvo can be loaded with high amounts of ginkgetin and berberine; (iv) ginkgetin plus berberine‐loaded EVAvo (EVAvo(B+G)) suppress activation of NFκB and NLRP3, and inhibit expression of pro‐inflammatory and atherogenic genes, specifically Cd36, Tnfα, Il1β and Il6; (v) EVAvo(B+G) attenuate oxidized low‐density lipoprotein (oxLDL)‐induced macrophage foam cell formation and (vi) EVAvo(B+G) inhibit oxLDL uptake but not its cell surface binding during foam cell formation. Overall, our results suggest that using EVAvo as a natural carrier of nutraceuticals may improve strategies to curb the progression of atherosclerosis by limiting inflammation and pro‐atherogenic responses. [ABSTRACT FROM AUTHOR]

Railway alignment optimization in earthquake‐prone mountainous (EPM) regions should quantify and trade off construction investments and seismic risks. Unfortunately, slight attention has been previously devoted to this trade‐off. To this end, based on the FEMA‐P58 methodology, a net present value (NPV) model of risk avoidance is presented and solved. In the model, alignment alternatives are first segmented into structural groups with different probabilistic seismic fragility curves, which are then used to generate structural repair cost and repair time curves. Afterward, a probabilistic seismic hazard curve is introduced to estimate the expected annual repair cost and time for computing railway direct and indirect seismic losses. Hence, the railway total annual loss caused by seismic activity can be obtained. Next, a benefit–cost analysis is performed to combine construction cost and seismic loss as the risk‐cost NPV. To optimize this objective function, a particle swarm algorithm is used as the basic approach. For implementing the probabilistic seismic performance analysis, a Monte Carlo simulation (MCS) is employed as the risk assessment module. Furthermore, due to the computationally intensive nature of MCS, a CPU‐based parallelization is embedded into the algorithm to expedite the search. Finally, the proposed model and method are applied to a representative real‐world railway case in an EPM region. Their effectiveness is discussed and verified in five experiments, including algorithm convergence analysis, alignment solution comparison, seismic risk interpretation, computational efficiency test, and a specific sensitivity analysis. [ABSTRACT FROM AUTHOR]

Exploration of medicines for efficient and safe management of metabolic‐associated fatty liver disease (MAFLD) remains a challenge. Obeticholic acid (OCA), a selective farnesoid X receptor agonist, has been reported to ameliorate injury and inflammation in various liver diseases. However, its clinical application is mainly limited by poor solubility, low bioavailability, and potential side effects. Herein a hepatic‐targeted nanodrugs composed of OCA and cholesterol‐lowering atorvastatin (AHT) with an ideal active pharmaceutical ingredient (API) content for orally combined treatment of MAFLD is created. Such carrier‐free nanocrystals (OCAHTs) are self‐assembled, not only improving the stability in gastroenteric environments but also achieving hepatic accumulation through the bile acid transporter‐mediated enterohepatic recycling process. Orally administrated OCAHT outperforms the simple combination of OCA and AHT in ameliorating of liver damage and inflammation in both acetaminophen‐challenged mice and high‐fat diet‐induced MAFLD mice with less systematic toxicity. Importantly, OCAHT exerts profoundly reverse effects on MAFLD‐associated molecular pathways, including impairing lipid metabolism, reducing inflammation, and enhancing the antioxidation response. This work not only provides a facile bile acid transporter‐based strategy for hepatic‐targeting drug delivery but also presents an efficient and safe full‐API nanocrystal with which to facilitate the practical translation of nanomedicines against MAFLD. [ABSTRACT FROM AUTHOR]

Apicomplexans, such as Plasmodium and Toxoplasma are obligate intracellular parasites that invade, replicate and finally EXIT their host cell. During replication within a parasitophorous vacuole (PV), the parasites establish an extensive F‐actin‐containing network that connects individual parasites and is required for material exchange, recycling and the final steps of daughter cell assembly. After multiple rounds of replication, the parasites exit the host cell involving multiple signalling cascades, disassembly of the network, secretion of microneme proteins and activation of the acto‐myosin motor. Blocking the host cell EXIT process leads to the formation of large PVs, making the screening for genes involved in exiting the cell relatively straightforward. Given that apicomplexans are highly diverse from other eukaryotes, approximately 30% of all genes are annotated as hypothetical, some apicomplexan‐specific factors are likely to be critical during EXIT. This motivated several labs to design and perform forward genetic and phenotypic screens using various approaches, such as random insertion mutagenesis, temperature‐sensitive mutants and, more recently, CRISPR/Cas9‐mediated targeted editing and conditional mutagenesis. Here we will provide an overview of the technological developments over recent years and the most successful stories that led to the identification of new critical factors in Toxoplasma gondii. [ABSTRACT FROM AUTHOR]

Cone‐beam computed tomography (CBCT) system can provide real‐time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology. [ABSTRACT FROM AUTHOR]

The effect of niobium ions with high‐valence doping on high‐voltage LiNi0.5Mn1.5O4 (LNMO) materials was investigated. LiNi0.5Mn1.5−xNbxO4 was prepared by doping high‐valent niobium ions into LiNi0.5Mn1.5O4 material using the organic assisted combustion method. The experimental samples were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X‐ray diffraction (XRD), X‐ray photoelectron spectroscopy (XPS), electrochemical impedance (EI), and cyclic voltammetry (CV) analysis. The experimental results show that ‐doping with high‐valence niobium ions changes the orientation of the crystal plane growth of spinel particles, and the morphology of these particles changes from the octahedral shape before doping to the spherical shape after doping. With the increase in doping amount, the crystal structure changes gradually, resulting in the Li0.96Nb1.01O3 impurity phase. The doping of high valence‐niobium ions increases the content of Mn3+ in the material, resulting in the appearance of a 4 V discharge platform and the formation of a 4.7 and 4 V discharge platforms. The doping of Nb can improve the cycling stability of LiNi0.5Mn1.5O4 material, but the specific capacity of the material is reduced. [ABSTRACT FROM AUTHOR]

Summary: Histone H3 lysine‐4 trimethylation (H3K4me3) activating drought‐responsive genes in plants for drought adaptation has long been established, but the underlying regulatory mechanisms are unknown.Here, using yeast two‐hybrid, bimolecular fluorescence complementation, biochemical analyses, transient and CRISPR‐mediated transgenesis in Populus trichocarpa, we unveiled in this adaptation a regulatory interplay between chromatin regulation and gene transactivation mediated by an epigenetic determinant, a PtrSDG2‐1–PtrCOMPASS (complex proteins associated with Set1)‐like H3K4me3 complex, PtrSDG2‐1–PtrWDR5a‐1–PtrRbBP5‐1–PtrAsh2‐2 (PtrSWRA).Under drought conditions, a transcription factor PtrAREB1‐2 interacts with PtrSWRA, forming a PtrSWRA–PtrAREB1‐2 pentamer, to recruit PtrSWRA to specific promoter elements of drought‐tolerant genes, such as PtrHox2, PtrHox46, and PtrHox52, for depositing H3K4me3 to promote and maintain activated state of such genes for tolerance. CRISPR‐edited defects in the pentamer impaired drought tolerance and elevated expression of PtrHox2, PtrHox46, or PtrHox52 improved the tolerance as well as growth in P. trichocarpa.Our findings revealed the identity of the underlying H3K4 trimethyltransferase and its interactive arrangement with the COMPASS for catalysis specificity and efficiency. Furthermore, our study uncovered how the H3K4 trimethyltransferase–COMPASS complex is recruited to the effector genes for elevating H3K4me3 marks for improved drought tolerance and growth/biomass production in plants. [ABSTRACT FROM AUTHOR]

A meta‐analysis was conducted to evaluate the effects of loose combined cutting seton surgery on wound healing and pain in patients with high anal fistula, aiming to provide evidence‐based medical evidence for surgical method selection for these patients. A comprehensive computerized search of PubMed, Cochrane Library, EMBASE, Wanfang and China National Knowledge Infrastructure databases was conducted to collect all relevant studies published up to November 2023, evaluating the effects of loose combined cutting seton surgery in treating patients with high anal fistulas. Two researchers independently screened, extracted data, and assessed the quality of the identified studies. RevMan 5.4 software was employed for data analysis. Overall, 16 articles were included, comprising 1124 patients, with 567 undergoing loose combined cutting seton surgery and 557 undergoing simple cutting seton surgery. The analysis revealed patients undergoing loose combined cutting seton surgery had a higher rate of postoperative wound healing (97.44% vs. 81.69%, odds ratio [OR]: 7.49, 95% confidence interval [CI]: 4.29–13.10, p < 0.00001), shorter wound healing time (standardized mean differences [SMD]: −1.48, 95% CI: −1.89 to −1.08, p < 0.00001), lower postoperative wound pain scores (SMD: −2.51, 95% CI: −3.51 to −1.51, p < 0.00001), and a lower rate of postoperative complications (3.43% vs. 20.83%, OR: 0.13, 95% CI: 0.05–0.31, p < 0.00001). The current evidence suggests that compared to simple cutting seton surgery, loose combined cutting seton surgery in treating high anal fistulas can promote postoperative wound healing, shorten wound healing time, alleviate pain, and reduce the incidence of postoperative complications, making it a worthy clinical practice for widespread application. [ABSTRACT FROM AUTHOR]