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Abstract Background Hepatitis B virus (HBV) infection is a persistent global public health problem, and curing for chronic hepatitis B (CHB) through the application of existing antiviral drugs is beset by numerous challenges. The viral protein HBx is a critical regulatory factor in the life cycle of HBV. Targeting HBx is a promising possibility for the development of novel therapeutic strategies. Methods The Nano-Glo® HiBiT Lysis Detection System was used to screen the herbal monomer compound library for compounds that inhibit HBx expression. Western blotting was used to examine proteins expression. Southern blotting or Northern blotting were used to detect HBV DNA or HBV RNA. ELISA was performed to detect the HBsAg level. The effect of asiatic acid on HBV in vivo was investigated by using recombinant cccDNA mouse model. Results Asiatic acid, an extract of Centella asiatica, significantly reduced the HBx level. Mechanistic studies demonstrated that asiatic acid may promote the degradation of HBx in an autophagy pathway-dependent manner. Subsequently, asiatic acid was found to reduce the amount of HBx bound to covalently closed circular DNA (cccDNA) microchromosomes, and repressive chromatin modifications then occurred, ultimately inhibiting cccDNA transcriptional activity. Moreover, in HBV-infected cells and a mouse model of persistent HBV infection, asiatic acid exhibited potent anti-HBV activity, as evidenced by decreased levels of HBV RNAs, HBV DNA and HBsAg. Conclusions Asiatic acid was identified as a compound that targets HBx, revealing its potential for application as an anti-HBV agent.

Abstract Phenotypes play a fundamental role in medical genetics, serving as external manifestations of underlying genotypes. Deep phenotyping, a cornerstone of precision medicine, involves precise multi-system phenotype assessments, facilitating disease subtyping and genetic understanding. Despite their significance, the field lacks standardized protocols for accurate phenotype evaluation, hindering clinical comprehension and research comparability. We present a comprehensive workflow of deep phenotyping for rare bone diseases from the Genetics Clinic of Skeletal Deformity at Peking Union Medical College Hospital. Our workflow integrates referral, informed consent, and detailed phenotype evaluation through HPO standards, capturing nuanced phenotypic characteristics using clinical examinations, questionnaires, and multimedia documentation. Genetic testing and counseling follow, based on deep phenotyping results, ensuring personalized interventions. Multidisciplinary team consultations facilitate comprehensive patient care and clinical guideline development. Regular follow-up visits emphasize dynamic phenotype reassessment, ensuring treatment strategies remain responsive to evolving patient needs. In conclusion, this study highlights the importance of deep phenotyping in rare bone diseases, offering a standardized framework for phenotype evaluation, genetic analysis, and multidisciplinary intervention. By enhancing clinical care and research outcomes, this approach contributes to the advancement of precision medicine in the field of medical genetics.

Abstract The HBV core protein (HBc) is an important viral protein of HBV that plays an indispensable role in the lifecycle of HBV, including capsid assembly and transport, reverse transcription and virus release. In recent years, evidence has shown that HBc may be involved in the malignant progression of HCC. Thus, HBc is an attractive target for antiviral agents and provides a new strategy for the treatment of HBV-related HCC. Here, we identified a novel anti‐HBc compound—colchicine, an alkaloid compound—that promoted selective autophagic degradation of HBc through the AMPK/mTOR/ULK1 signalling pathway. We further confirmed that colchicine promoted the selective autophagy of HBc by enhancing the binding of HBc to the autophagy receptor p62. Finally, we evaluated the effects of colchicine on HBV replication and HBc-mediated HCC metastasis in vitro and in vivo. Our research indicated that the inhibitory effects of colchicine on HBV and HBV-related HCC depend on the selective autophagic degradation of HBc. Thus, colchicine is not only a promising therapeutic strategy for chronic hepatitis B but also a new treatment for HBV-related HCC.

Abstract Background β-Arbutin, a hydroquinone glucoside found in pears, bearberry leaves, and various plants, exhibits antioxidant, anti-inflammatory, antimicrobial, and anticancer effects. β-Arbutin has wide applications in the pharmaceutical and cosmetic industries. However, the limited availability of high-performance strains limits the biobased production of β-arbutin. Results This study established the β-arbutin biosynthetic pathway in C. glutamicum ATCC13032 by introducing codon-optimized ubiC, MNX1, and AS. Additionally, the production titer of β-arbutin was increased by further inactivation of csm and trpE to impede the competitive metabolic pathway. Further modification of the upstream metabolic pathway and supplementation of UDP-glucose resulted in the final engineered strain, C. glutamicum AR11, which achieved a β-arbutin production titer of 7.94 g/L in the optimized fermentation medium. Conclusions This study represents the first successful instance of de novo β-arbutin production in C. glutamicum, offering a chassis cell for β-arbutin biosynthesis.

Abstract This paper proposes an estimation approach following the constructive identification strategy of Athey and Haile, and Gentry and Li with adaption in the context of ascending auctions with selective entry. Our estimators are shown to be consistent in a large sample and to perform well in a finite sample by a simulation study. We apply our estimation approach to the Alibaba online judicial auctions of used cars to recover the bounds of conditional value distribution and the entry cost. The bounds estimates of both conditional value distribution and entry cost are quite tight (resp., relatively wide) for middle‐valued (resp., low‐valued or high‐valued) signal, and the cumulative distribution functions of conditional value distribution given signal comply with the law of ordered dominance. Finally, our counterfactual analysis indicates that (i) the ascending auction yields a higher revenue than the first‐price sealed bid auction, and (ii) the revenue can be improved significantly when the entry cost is cut by half.

BackgroundRecent findings highlight the significant impact of intestinal fungi on the complex makeup of the gut microbiota and human health, challenging past oversights. However, a lack of thorough systematic and quantitative analyses remains. This study aims to address this gap by thoroughly examining the current research on gut fungi. Through analyzing developments and unique features in this area, our goal is to foster a deeper understanding and identify future research pathways.MethodsWe performed an extensive bibliometric analysis on documents from 2000 to 2023, sourced from the Web of Science Core Collection (WoSCC). Utilizing advanced visualization tools such as VOSviewer, CiteSpace, and Bibliometrix R, we meticulously examined and illustrated the data in scientific landscapes and networks.ResultsA total of 1434 papers were analyzed, revealing a substantial increase in publication volume over the past two decades, particularly in 2020. Contributions came from 67 countries, 2178 institutions, and 8,479 authors. China led in publication output with 468 articles, followed by the University of California with 84 articles, and ZHANG F as the most prolific author with 17 articles. Emerging research areas such as “Fungal-Bacteria Interactions,” “Gut Fungus and Gut-Brain Axis,” and “Gut Fungus and Immunity” are expected to attract growing interest in the future.ConclusionThis extensive bibliometric analysis offers a current overview of scholarly efforts concerning intestinal fungi, highlighting the predominant landscape in this field. These insights can assist scholars in identifying appropriate publication avenues, forming collaborative relationships, and enhancing understanding of key themes and emerging areas, thereby stimulating future research endeavors.

IntroductionIn the search for sustainable development, urban eco-development is becoming a core agenda for all countries. China’s low-carbon city pilot (LCCP) policy is an important initiative to promote urban low-carbon governance. And exploring the direction of LCCP policy is an important step towards sustainable urban development.MethodsSuper-SBM is employed to calculate urban ecological efficiency using panel data from 254 prefecture-level cities between 2007 and 2020. The methods of kernel density estimation and spatial Markov chains are applied to the spatial analysis of urban ecological efficiency. The spatial analyses examine the spatiotemporal patterns and dynamic evolving trends of urban ecological efficiency. Additionally, the multiperiod difference-in-differences method is used to assess the impact of the LCCP policy on urban ecological efficiency. On this basis, we apply the method of mechanism analysis to discuss the influence mechanism.ResultsThe results indicate that urban ecological efficiency gradually forms a continuous spatial clustering pattern, although there is a widening tendency in the absolute differences. In the subsequent transfer process, the spatial factor plays a highly significant role. Benchmark regressions and auxiliary robustness tests demonstrate that the LCCP policy is effective in improving urban ecological efficiency. Further analysis shows that the effect of LCCP policies on ecological efficiency can be transmitted by promoting green technology innovation as well as facilitating a low-carbon transition in the energy mix. The above findings indicate the presence of the "Green Innovation Effect" and the "Decoupling Effect".DiscussionThese discoveries enhance the theoretical framework of urban ecology and offer valuable insights for other regions seeking to implement low-carbon urban governance.

Abstract Background The Ehlers-Danlos syndromes (EDS) are a group of rare hereditary connective tissue disorders. EDS is clinically and genetically heterogeneous and usually involves multiple systems. There are 14 subtypes of EDS with hallmark features including joint hypermobility, skin hyperextensibility, and tissue fragility. The clinical manifestations and their severity differ among the subtypes, encompassing recurrent joint dislocations, scoliosis, arterial aneurysm and dissection, and organ rupture. Challenges in diagnosis and management arise from the complexity of the disease, which is further complicated by its rarity. The development of clinical guidelines and implementation of coordinated multi-disciplinary team (MDT) approaches have emerged as global priorities. Main body Chinese Multi-Disciplinary Working Group on the Ehlers-Danlos Syndromes was therefore established. Healthcare professionals were recruited from 25 top hospitals across China. The experts are specialized in 24 fields, including genetics, vascular surgery, dermatology, and orthopedics, as well as nursing care, rehabilitation, psychology, and nutrition. Based on GRADE methodology, the Guidelines were written by the Group supervised by methodologists, following a systemic review of all 4453 articles in PubMed published before August 9, 2023, using the search term “Ehlers Danlos”. A coordinated MDT approach for the diagnosis and management of EDS is highly recommended by the Group, along with 29 specific recommendations addressing key clinical questions. In addition to the treatment plan, the Guidelines also emphasize integrating support from nursing care, rehabilitation, psychology, and nutrition. This integration not only facilitates recovery in hospital settings, but most importantly, the transition from an illness-defined life to a more “normalized” life. Conclusion The first guidelines on EDS will shorten the diagnostic odyssey and solve the unmet medical needs of the patients. This article is a synopsis of the full guidelines.

The WNT/β-catenin signaling pathway plays crucial roles in tumorigenesis and relapse, metastasis, drug resistance, and tumor stemness maintenance. In most tumors, the WNT/β-catenin signaling pathway is often aberrantly activated. The therapeutic usefulness of inhibition of WNT/β-catenin signaling has been reported to improve the efficiency of different cancer treatments and this inhibition of signaling has been carried out using different methods including pharmacological agents, short interfering RNA (siRNA), and antibodies. Here, we review the WNT-inhibitory effects of some FDA-approved drugs and natural products in cancer treatment and focus on recent progress of the WNT signaling inhibitors in improving the efficiency of chemotherapy, immunotherapy, gene therapy, and physical therapy. We also classified these FDA-approved drugs and natural products according to their structure and physicochemical properties, and introduced briefly their potential mechanisms of inhibiting the WNT signaling pathway. The review provides a comprehensive understanding of inhibitors of WNT/β-catenin pathway in various cancer therapeutics. This will benefit novel WNT inhibitor development and optimal clinical use of WNT signaling-related drugs in synergistic cancer therapy.

Abstract Background Progressive hepatitis B virus (HBV) infection can result in cirrhosis, hepatocellular cancer, and chronic hepatitis. While antiviral drugs that are now on the market are efficient in controlling HBV infection, finding a functional cure is still quite difficult. Identifying host factors involved in regulating the HBV life cycle will contribute to the development of new antiviral strategies. Zinc finger proteins have a significant function in HBV replication, according to earlier studies. Zinc finger protein 148 (ZNF148), a zinc finger transcription factor, regulates the expression of various genes by specifically binding to GC-rich sequences within promoter regions. The function of ZNF148 in HBV replication was investigated in this study. Methods HepG2-Na+/taurocholate cotransporting polypeptide (HepG2-NTCP) cells and Huh7 cells were used to evaluate the function of ZNF148 in vitro. Northern blotting and real-time PCR were used to quantify the amount of viral RNA. Southern blotting and real-time PCR were used to quantify the amount of viral DNA. Viral protein levels were elevated, according to the Western blot results. Dual-luciferase reporter assays were used to examine the transcriptional activity of viral promoters. ZNF148’s impact on HBV in vivo was investigated using an established rcccDNA mouse model. Results ZNF148 overexpression significantly decreased the levels of HBV RNAs and HBV core DNA in HBV-infected HepG2-NTCP cells and Huh7 cells expressing prcccDNA. Silencing ZNF148 exhibited the opposite effects in both cell lines. Furthermore, ZNF148 inhibited the activity of HBV ENII/Cp and the transcriptional activity of cccDNA. Mechanistic studies revealed that ZNF148 attenuated retinoid X receptor alpha (RXRα) expression by binding to the RXRα promoter sequence. RXRα binding site mutation or RXRα overexpression abolished the suppressive effect of ZNF148 on HBV replication. The inhibitory effect of ZNF148 was also observed in the rcccDNA mouse model. Conclusions ZNF148 inhibited HBV replication by downregulating RXRα transcription. Our findings reveal that ZNF148 may be a new target for anti-HBV strategies.

Abstract Background Radical nephroureterectomy (RNU) is the primary treatment strategy for upper tract urothelial carcinoma (UTUC). However, the intravesical recurrence occurs in 20–50% of all patients. The specific effect of subsequent bladder cancer (SBCa) on survival remains unclear. Therefore, we investigated the effect of SBCa following RNU in patients with UTUC. Methods PubMed, EMBASE, and Cochrane Library were exhaustively searched for studies comparing oncological outcomes between SBCa and without SBCa. Standard cumulative analyses using hazard ratios (HR) with 95% confidence intervals (CI) were performed using Review Manager (version 5.3). Results Five studies involving 2057 patients were selected according to the predefined eligibility criteria. Meta-analysis of cancer-specific survival (CSS) and overall survival (OS) revealed no significant differences between the SBCa and non-SBCa groups. However, subgroup analysis of pT0-3N0M0 patients suggested that people with SBCa had worse CSS (HR = 5.13, 95%CI 2.39–10.98, p

In non-invasive blood glucose measurement, the sensitivity of glucose-induced optical signals within human tissue is a crucial reference point. This study evaluates the sensitivity of glucose-induced diffuse reflectance in the 1000–1700 nm range. A key factor in understanding this sensitivity is the rate at which the scattering coefficient changes due to glucose, as it is significantly higher than in non-living media and predominantly influences the diffuse light signal level when blood glucose levels change. The study measured and calculated the changes in the scattering coefficient at 1314 nm, a wavelength chosen for its minimal interference from glucose absorption and other bodily constituents. Based on the Mie scattering theory and the results at 1314 nm, the changes in the scattering coefficient within the 1000–1700 nm range were estimated. Subsequently, the sensitivity of the glucose signal across this range was determined through Monte Carlo (MC) simulations. The findings from 25 human trials indicate that the measured sensitivities at five other typical wavelengths within this band generally align with the sensitivities calculated using the aforementioned method. This research can guide the identification of blood glucose signals and the selection of wavelengths for non-invasive blood glucose measurements.

The design and development of highly efficient electrocatalysts for oxygen evolution reaction (OER) are critical for renewable energy generation. Ni‐based electrocatalysts are widely used in the water electrolysis process. In this work, heterostructure consisting of selenides and layered double hydroxides (LDH) named (Co, Ni)Se4@NiFe‐LDH, are prepared by an LDH‐based strategy, in which the electronic structure of Ni active sites is regulated by interfacial electron interaction. The (Co, Ni)Se4@NiFe‐LDH shows an optimized charge distribution of Ni sites and excellent catalytic activity. The effective charge modulation results in lowering the energy barrier of OOH* intermediate formation and adequate adsorption strength of the intermediates on Ni‐active sites, which improves the kinetics of OER. Specifically, the (Co, Ni)Se4@NiFe‐LDH only requires an overpotential of 237 mV to reach the current density of 10 mA cm−2 under alkaline conditions. The results of this work demonstrate that reasonable engineering of heterostructure is an effective strategy to improve the intrinsic property of OER electrocatalysts for water splitting.

Abstract Background Our study aims to investigate the association between the serum neutrophil-to-lymphocyte ratio (NLR) and interstitial cystitis (IC), as well as to explore whether NLR can serve as a diagnostic marker to distinguish IC from overactive bladder (OAB). We postulate that elevated NLR levels are intricately linked to the onset and clinical presentation of IC, and that the NLR profiles in OAB patients exhibit discernible disparities from those of IC patients. Methods In a retrospective analysis, we scrutinized the medical records of 70 women diagnosed with IC/BPS, 20 women diagnosed with OAB, and a randomly selected cohort of 150 healthy women who underwent physical examinations during the same temporal frame. A comprehensive panel of blood tests was administered to all participants, and NLR was determined through the calculation of the neutrophil-to-lymphocyte proportion. Additionally, symptom assessment questionnaires and urination diaries were collected from IC/BPS patients. Results NLR levels exhibited significant distinctions among the IC/BPS, Normal, and OAB groups (P

Abstract While macrophage phagocytosis is an immune defense mechanism against invading cellular organisms, cancer cells expressing the CD47 ligand send forward signals to repel this engulfment. Here we report that the reverse signaling using CD47 as a receptor additionally enhances a pro-survival function of prostate cancer cells under phagocytic attack. Although low CD47-expressing cancer cells still allow phagocytosis, the reverse signaling delays the process, leading to incomplete digestion of the entrapped cells and subsequent tumor hybrid cell (THC) formation. Viable THCs acquire c-Myc from parental cancer cells to upregulate both M1- and M2-like macrophage polarization genes. Consequently, THCs imitating dual macrophage features can confound immunosurveillance, gaining survival advantage in the host. Furthermore, these cells intrinsically express low levels of androgen receptor and its targets, resembling an adenocarcinoma-immune subtype of metastatic castration-resistant prostate cancer. Therefore, phagocytosis-generated THCs may represent a potential target for treating the disease.

The Haiyang-2D (HY2D) satellite is the fourth ocean dynamics environment monitoring satellite launched by China. The satellite operates on a re-entry frozen orbit, which necessitates orbital maneuvers to maintain its designated path once the satellite’s sub-satellite point deviates beyond a certain threshold. However, the execution of orbit maneuvers presents a significant challenge to the field of Precise Orbit Determination (POD). The thesis selects the on-board GPS data of HY2D satellite in December 2023 and five maneuvering days of that year. Employing a multifaceted approach that includes the assessment of observational data quality, orbit overlap, external orbit validation, and SLR (Satellite Laser Ranging) verification, the research delves into precise orbit determination during both maneuver and non-maneuver periods. The results indicate that: (1) The average number of satellites tracked by the receiver is 6.4; (2) During the non-maneuver periods, the average RMS (Root Mean Square) value of the radial difference in the 6-h overlapping arc segment is 0.66 cm, and the three-dimensional position difference is about 1.16 cm; (3) When compared with the precision science orbits (PSO) provided by CNES (Centre National d’Études Spatiales), the average values of the RMS values of the differences in the radial (R), transverse (T), and normal (N) directions during the non-maneuver and maneuver periods are respectively 1.32 cm, 2.31 cm, 1.92 cm and 3.04 cm, 8.78 cm, 2.72 cm. (4) The SLR verification of the orbit revealed a residual RMS of 2.24 cm. This suggests that by incorporating the modeling of maneuver forces during the maneuver periods, the impact of orbital maneuvers on orbit determination can be mitigated.

Abstract Tomato (Solanum lycopersicum) is one of the most important vegetable crops in the world and abiotic stresses often cause serious problems in tomato production. It is thus important to identify new regulators in stress response and to devise new approaches to promote stress tolerance in tomato. Previous studies have shown that small secreted peptides (SSPs) are important signal molecules regulating plant growth and stress response by mediating intercellular communication. However, little is known about tomato SSPs, especially their roles in responding to abiotic stresses. Here we report the identification of 1,050 putative SSPs in the tomato genome, 557 of which were classified into 38 known SSP families based on their conserved domains. GO and transcriptome analyses revealed that a large proportion of SlSSPs might be involved in abiotic stress response. Further analysis indicated that stress response related cis-elements were present on the SlCEP promotors and a number of SlCEPs were significantly upregulated by drought treatments. Among the drought-inducible SlCEPs, SlCEP10 and SlCEP11b were selected for further analysis via exogenous application of synthetic peptides. The results showed that treatments with both SlCEP10 and SlCEP11b peptides enhanced tomato drought stress tolerance, indicating the potential roles of SlSSPs in abiotic stress response. Graphical Abstract

Abstract Importance Both the morbidity and mortality of prostate cancer are increasing worldwide. Updated evaluations of prostate cancer burden and its global, regional and national patterns are essential for formulating effective preventive strategies. Objective To investigate prostate cancer incidence, mortality, and disability-adjusted life years (DALYs) between 1990 and 2019 to facilitate preventive measures and control planning. Methods Annual incident cases, deaths, DALYs, age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and age-standardized DALYs rates (ASDRs) of prostate cancer between 1990 and 2019 were derived from the Global Burden of Diseases study 2019. Percentage changes in incident cases, deaths and DALYs and estimated annual percentage changes (EAPCs) in ASIRs, ASMRs and ASDRs were calculated to quantify temporal trends. Correlations between EAPCs and socio-demographic index (SDI) and universal health coverage index (UHCI) were evaluated by Pearson correlation analyses. Results Globally, the number of incident cases, deaths, and DALYs of prostate cancer increased by 116.11%, 108.94%, and 98.25% from 1990 to 2019, respectively. The ASIR increased by an average of 0.26% (95% CI: 0.14%, 0.37%) per year between 1990 and 2019, while the ASMR and ASDR decreased by an average of – 0.75% (95% CI: – 0.84%, – 0.67%) and – 0.71% (95% CI: – 0.78%, – 0.63%) per year in this period, respectively. Epidemic trends in the burdens of prostate cancer were not uniform throughout different groups of SDI or geography. The burdens of prostate cancer varied across SDI regions, with an increasing trend in ASIR, ASMR, and ASDR in low and low-middle SDI regions between 1990 and 2019. A significant positive correlation between the EAPC in ASIR and UHCI was observed in countries with a UHCI

Grasslands are one of the largest coupled human-nature terrestrial ecosystems on Earth, and severe anthropogenic-induced grassland ecosystem function declines have been reported recently. Understanding factors influencing grassland ecosystem functions is critical for making sustainable management policies. Canopy structure is an important factor influencing plant growth through mediating within-canopy microclimate (e.g., light, water, and wind), and it is found coordinating tightly with plant species diversity to influence forest ecosystem functions. However, the role of canopy structure in regulating grassland ecosystem functions along with plant species diversity has been rarely investigated. Here, we investigated this problem by collecting field data from 170 field plots distributed along an over 2000 km transect across the northern agro-pastoral ecotone of China. Aboveground net primary productivity (ANPP) and resilience, two indicators of grassland ecosystem functions, were measured from field data and satellite remote sensing data. Terrestrial laser scanning data were collected to measure canopy structure (represented by mean height and canopy cover). Our results showed that plant species diversity was positively correlated to canopy structural traits, and negatively correlated to human activity intensity. Canopy structure was a significant indicator for ANPP and resilience, but their correlations were inconsistent under different human activity intensity levels. Compared to plant species diversity, canopy structural traits were better indicators for grassland ecosystem functions, especially for ANPP. Through structure equation modeling analyses, we found that plant species diversity did not have a direct influence on ANPP under human disturbances. Instead, it had a strong indirect effect on ANPP by altering canopy structural traits. As to resilience, plant species diversity had both a direct positive contribution and an indirect contribution through mediating canopy cover. This study highlights that canopy structure is an important intermediate factor regulating grassland diversity-function relationships under human disturbances, which should be included in future grassland monitoring and management.

Sorbus caloneura has high ornamental and medicinal value but is endangered, and significant effort is required to preserve this natural resource. In this study, the stem and sterilized leaves of S. caloneura were used to explore the effects of different plant hormones basic medium type, initial callus quality, initial liquid volume, and ratio of old liquid culture medium to new on stem proliferation, regeneration and callus suspension culture. Naphthylacetic acid (NAA) and 6-benzyladenine (6-BA) significantly affected the proliferation of stem tissue. Murashige and Skoog (MS) basal medium supplemented with 1.75 mg/L 6-BA, 0.25 mg/L NAA, and 0.25 mg/L indole butyric acid (IBA) yielded a proliferation rate of 100%, with an average number of adventitious shoots per stem of 4.9. The best callus induction was observed with MS basal medium containing 0.5 mg/L 6-BA, 1 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D), and 0.2 mg/L thidiazuron (TDZ). The adventitious shoots were directly induced by MS basal medium containing 5.0 mg/L 6-BA, 0.5 mg/L NAA, and 1.5 mg/L kinetin (KT) and indirectly induced by medium containing 3.0 mg/L 6-BA, 0.3 mg/L NAA, and 0.1 mg/L TDZ. NAA significantly affected rooting rate, with ideal conditions found to be medium supplemented with 0.2 mg/L NAA and 1.5 mg/L IBA. MS basal medium with 4.5 g of calli and 120 mL of liquid culture medium without retention of the original culture medium yielded the best suspension effect for callus proliferation. Taken together, the results of this study lay a foundation for the breeding, preservation of germplasm resources, and genetic transformation of S. caloneura.

Abstract Tetracycline (TET) is a broad-spectrum antibiotic commonly used in the treatment of animals. TET residues in food inevitably threaten human health. High-performance analytical techniques for TET detection are required in food quality assessment. The objective of this study was to establish a label-free fluorescent biosensor for TET detection using specific aptamer-templated silver nanoclusters (AgNCs). An aptamer with a high specific binding ability to TET was used to synthesize a novel DNA-templated AgNCs (DNA-AgNCs). When TET is present, the aptamer’s conformation switched from an antiparallel G-quadruplex to a hairpin structure, altering the connection between AgNCs and the aptamer. Following the transformation of AgNCs into large sized silver nanoparticles (AgNPs), a fluorescence decrease was detected. When used to detect TET in milk, the proposed biosensor displayed high sensitivity and selectivity, with a limit of detection of 11.46 ng/mL, a linear range of 20 ng/mL−10 g/mL, and good recoveries of 97.7–114.6% under optimized conditions. These results demonstrate that the proposed biosensor was successfully used to determine TET quantitatively in food samples, suggesting that our method provides an efficient and novel reference for detecting antibiotics in food while expanding the application of DNA-AgNCs in related fields.

RNA translation is the rate-limiting step when cells synthesize proteins. Elevating translation efficiency (TE) is intuitively beneficial. Particularly, when viruses invade host cells, how to compete with endogenous RNAs for efficient translation is a major issue to be resolved. We collected millions of worldwide SARS-CoV-2 sequences during the past year and traced the dynamics of allele frequency of every mutation. We defined adaptive and deleterious mutations according to the rise and fall of their frequencies along time. For 5ʹUTR and synonymous mutations in SARS-CoV-2, the selection on TE is evident near start codons. Adaptive mutations generally decrease GC content while deleterious mutations increase GC content. This trend fades away with increasing distance to start codons. Mutations decreasing GC content near start codons would unravel the complex RNA structure and facilitate translation initiation, which are beneficial to SARS-CoV-2, and vice versa. During this evolutionary arms race between human and virus, SARS-CoV-2 tries to improve its cis elements to compete with host RNAs for rapid translation.

CH4 is one of the most important greenhouse gases responsible for climate change. The effect of algal decomposition on CH4 emission fluxes in aquaculture environments is unknown. This study determined the relative abundance of methanogens in aquaculture in northern China. We determined various parameters in the water and sediment after the decomposition of Chaetomorpha valida. The results showed that the relative abundance of methanogens increased significantly during the decomposition of C. valida. The average CH4 emission flux was 50.64 mg m-2 h-1 when the density of C. valida was 25 mg cm-3, which was 11 times higher than that at a density of 0 mg cm-3. The concentrations of dissolved oxygen (DO), nitrite, nitrate and sulfate in the aquaculture pond significantly decreased during the decomposition of C. valida. The formation of a strong anaerobic reduction environment promoted the formation and release of CH4. Our results confirmed that the decomposition of C. valida enhanced the CH4 emission flux. The average CH4 emission fluxes ranged from 4.62 to 50.64 mg m-2 h-1. It is particularly important to remove decomposed algae in a timely manner and control greenhouse gas emissions from aquaculture ponds to mitigate climate change.

Gene therapy has become an essential treatment for optic nerve injury (ONI) in recent years, and great strides have been made using animal models. ONI, which is characterized by the loss of retinal ganglion cells (RGCs) and axons, can induce abnormalities in the pupil light reflex, visual field defects, and even vision loss. The eye is a natural organ to target with gene therapy because of its high accessibility and certain immune privilege. As such, numerous gene therapy trials are underway for treating eye diseases such as glaucoma. The aim of this review was to cover research progress made in gene therapy for ONI. Specifically, we focus on the potential of gene therapy to prevent the progression of neurodegenerative diseases and protect both RGCs and axons. We cover the basic information of gene therapy, including the classification of gene therapy, especially focusing on genome editing therapy, and then we introduce common editing tools and vector tools such as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) -Cas9 and adeno-associated virus (AAV). We also summarize the progress made on understanding the roles of brain derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), phosphatase-tensin homolog (PTEN), suppressor of cytokine signal transduction 3 (SOCS3), histone acetyltransferases (HATs), and other important molecules in optic nerve protection. However, gene therapy still has many challenges, such as misalignment and mutations, immunogenicity of AAV, time it takes and economic cost involved, which means that these issues need to be addressed before clinical trials can be considered.

Abstract Background The bifunctional methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase (MTHFD2) has been reported to play an oncogenic role in various types of cancers. However, the function of MTHFD2 in urothelial carcinomas of bladder (UCB) and its association with tumor immune infiltration remains unknown. We aim to examine the suitability of MTHFD2 to be a novel biomarker of bladder cancer and whether MTHFD2 is linked to immune infiltration. Methods RNA sequencing data and clinical information (bladder cancer samples: normal samples = 414: 19) were downloaded from The Cancer Genome Atlas official website. Western blot analysis was performed to detect MTHFD2 expression in human bladder cancer (BLCA) cells and normal urothelial cell line SV-HUC-1. Associations between MTHFD2 expression and clinicopathological features were analyzed using Mann Whitney U test or Kruskal-Wallis H test. The “survival” and “survminer” packages were utilized to plot Kaplan-Meier survival curves. Moreover, the gene set enrichment analysis (GSEA) was conducted using a clusterProfiler package. The correlation of MTHFD2 expression with immune infiltration level was estimated using the single sample GSEA (ssGSEA) algorithm. Furthermore, associations between MTHFD2 and immune checkpoint genes were evaluated using the correlation analysis. Results Transcriptome analysis manifested that MTHFD2 was highly expressed in UCB tissues than normal bladder tissues, which was further confirmed by western blot analysis in human BLCA cells and SV-HUC-1 cells. Moreover, MTHFD2 high expression was significantly associated with the advanced disease progression. Also, the high expression of MTHFD2 was correlated with poor prognosis, and MTHFD2 was considered as an independent prognostic factor for disease specific survival. Furthermore, a number of cancer-related pathways were enriched in MTHFD2 high group, including NF-κB activation, JAK/STAT, and cancer immunotherapy by PD1 blockade. Several immune checkpoint molecules were also strongly associated with MTHFD2 expression, including PDCD1, CD274, CTLA4, CD276, LAG3, HAVCR2, and TIGIT. Conclusions MTHFD2 expression was remarkably elevated in UCB, suggesting that MTHFD2 could be a promising biomarker for BLCA as well as novel target for anti-cancer immunotherapy since its close association with immune infiltration.

Abstract l-Ornithine, an important non-essential amino acid, has considerable medicinal value in the treatment of complex liver diseases. Microbial fermentation strategies using robust engineered strains have remarkable potential for producing l-ornithine. We showed that glucose and sucrose co-utilization accumulate more l-ornithine in Corynebacterium glutamicum than glucose alone. Further manipulating the expression of intracellular fructose-1-phosphate kinase through the deletion of pfkB1resulted in the engineered strain C. glutamicum SO30 that produced 47.6 g/L of l-ornithine, which represents a 32.8% increase than the original strain C. glutamicum SO26 using glucose as substrate (35.88 g/L). Moreover, fed-batch cultivation of C. glutamicum SO30 in 5-L fermenters produced 78.0 g/L of l-ornithine, which was a 78.9% increase in yield compared with that produced by C. glutamicum SO26. These results showed that manipulating the fructose metabolic pathway increases l-ornithine accumulation and provides a reference for developing C. glutamicum to produce valuable metabolites. Graphical Abstract

Abstract Nod-like receptor protein 3 (NLRP3), as an inflammatory regulator, has been implicated in acute kidney injury (AKI). Failed recovery after AKI can lead to chronic kidney disease (CKD). However, the role of NLRP3 in the AKI-CKD transition is still unknown. A mild or severe AKI mouse model was performed by using ischemia-reperfusion injury (IRI). We evaluated the renal NLRP3 expression in acute and chronic phases of ischemic AKI, respectively. Although serum creatinine (Cr) and blood urea nitrogen (BUN) levels in AKI chronic phase were equivalent to normal baseline, histological analysis and fibrotic markers revealed that severe AKI-induced maladaptive tubular repair with immune cell infiltration and fibrosis. Tubular damage was restored completely in mild AKI rather than in severe AKI. Of note, persistent overexpression of NLRP3 was also found in severe AKI but not in mild AKI. In the severe AKI-induced chronic phase, there was a long-term high level of NLRP3 in serum or urine. Overt NLRP3 was mainly distributed in the abnormal tubules surrounded by inflammatory infiltrates and fibrosis, which indicated the maladaptive repair. Renal Nlrp3 overexpression was correlated with infiltrating macrophages and fibrosis. Renal NLRP3 signaling-associated genes were upregulated after severe AKI by RNA-sequencing. Furthermore, NLRP3 was found increased in renal tubular epitheliums from CKD biopsies. Together, persistent NLRP3 overexpression was associated with chronic pathological changes following AKI, which might be a new biomarker for evaluating the possibility of AKI-CKD transition.

Methicillin-resistant Staphylococcus aureus (MRSA) causes an enormous illness burden, including skin and soft tissue infections (SSTIs), pneumonia, bloodstream infections (BSI), and sepsis. BSI are associated with significant patient morbidity and mortality worldwide. However, limited information is available on MRSA-related BSI in China. This study aimed to investigate the molecular characterization of 77 MRSA isolates recovered from hospitalized patients with BSI between 2012 and 2020 at three first-class tertiary hospitals in southern China based on multilocus sequence typing (MLST), spa typing, and staphylococcal cassette chromosome mec (SCCmec) typing. Overall, 13 clonal complexes (CCs) were identified, with CC59 and CC5 being the largest clusters, indicating high genetic diversity among BSI-causing MRSA isolates. ST59 was the most prevalent MLST type (22.1%). ST5/ST764-MRSA SCCmec II was the predominant adult MRSA clone, whereas ST59-MRSA SCCmec IV was the most common pediatric MRSA clone. ST5-t2460, ST764-t1084, and ST59-t437 were the most common types of adult MRSA isolates, whereas ST59-t437 and ST59-t172 were the predominant types of children’s MRSA isolates. ST59-SCCmec IV/V represented the most common clone among community acquired-MRSA isolates. ST5/ST764-SCCmec II was the most common type of hospital-associated MRSA isolate. The most prevalent toxin-encoding genes detected were hla, hld, icaA, and clfA (96.1–100%). Forty-three (100%, 43/43) isolates harbored more than 18 of the tested virulence genes in adults and eight virulence genes (23.5%, 8/34) in children. Virulence gene analysis revealed diversity among different clones: the positivity rates for the Panton-Valentine leukocidin (PVL) gene were 55.8 and 35.3% in adult and pediatric MRSA isolates, respectively; the genes seb–sei were present in all adult strains; seb–seg–sei–seo were present in all ST5, ST59, ST15, ST45, and ST22 adult strains; and seg–sei–sem–sen–seo were present in different clones, including ST15, ST45, and ST22 adult MRSA isolates and ST25, ST30, ST546, and ST72 children’s MRSA isolates. Adult MRSA isolates had significantly higher antibiotic resistance rates and virulence gene prevalence than pediatric MRSA isolates. For 8 years, this study provided epidemiological data on the molecular characteristics and virulence genes in different groups of MRSA BSI in China. Our findings may provide critical information for a better understanding of MRSA BSI.

Abstract Acute kidney injury (AKI) is associated with significant morbidity and its chronic inflammation contributes to subsequent chronic kidney disease (CKD) development. Yes-associated protein (YAP), the major transcriptional coactivator of the Hippo pathway, has been shown associated with chronic inflammation, but its role and mechanism in AKI-CKD transition remain unclear. Here we aimed to investigate the role of YAP in AKI-induced chronic inflammation. Renal ischemia/reperfusion (I/R) was used to induce a mouse model of AKI-CKD transition. We used verteporfin (VP), a pharmacological inhibitor of YAP, to treat post-IRI mice for a period, and evaluated the influence of YAP inhibition on long-term outcomes of AKI. In our results, severe IRI led to maladaptive tubular repair, macrophages infiltration, and progressive fibrosis. Following AKI, the Hippo pathway was found significantly altered with YAP persistent activation. Besides, tubular YAP activation was associated with the maladaptive repair, also correlated with interstitial macrophage infiltration. Monocyte chemoattractant protein 1 (MCP-1) was found notably upregulated with YAP activation. Of note, pharmacological inhibition of YAP in vivo attenuated renal inflammation, including macrophage infiltration and MCP-1 overexpression. Consistently, in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) induced YAP activation and MCP-1 overproduction whereas these could be inhibited by VP. In addition, we modulated YAP activity by RNA interference, which further confirmed YAP activation enhances MCP-1 expression. Together, we concluded tubular YAP activation with maladaptive repair exacerbates renal inflammation probably via promoting MCP-1 production, which contributes to AKI-CKD transition.

Objective: Based on TCGA database, a prediction model for 1-, 3-, and 5-year overall survival rates of gastric cancer (GC) patients was constructed by analyzing the critical risk factors affecting the prognosis of gastric cancer patients.Method: Clinicopathological features as well as gene signature of GC patients were obtained from TCGA database. Patients were randomly divided into a training cohort and an internal validation cohort. Independent predictors of GC prognosis were analyzed by univariate and multivariate Cox analyses to construct nomogram. The accuracy and reliability of the model was further validated by calibration curves, ROC curves, and C-indexes, and the clinical utility of the model was analyzed by decision analysis curves.Result: Age, sex, N stage, M stage, METTL16, RBM15, FMR1, IGFBP1, and FTO were significantly associated with the prognosis of GC patients, and these predictors were further included in the construction of nomogram. The C-indexes for the training cohort and validation set were 0.735 and 0.688, respectively. The results of the ROC curve analysis indicated that the area under the curve (AUC) exceeded 0.6 in training and validation sets at 1, 3, and 5 years.Conclusion: We have constructed and validated a nomogram that provides individual survival condition prediction for GC patients. The prognostic model integrating gene signatures and clinicopathological characteristics would help clinicians determine the prognosis of patients with GC and develop individualized treatment plans.

Abstract Background Precision agriculture is an emerging research field that relies on monitoring and managing field variability in phenotypic traits. An important phenotypic trait is biomass, a comprehensive indicator that can reflect crop yields. However, non-destructive biomass estimation at fine levels is unknown and challenging due to the lack of accurate and high-throughput phenotypic data and algorithms. Results In this study, we evaluated the capability of terrestrial light detection and ranging (lidar) data in estimating field maize biomass at the plot, individual plant, leaf group, and individual organ (i.e., individual leaf or stem) levels. The terrestrial lidar data of 59 maize plots with more than 1000 maize plants were collected and used to calculate phenotypes through a deep learning-based pipeline, which were then used to predict maize biomass through simple regression (SR), stepwise multiple regression (SMR), artificial neural network (ANN), and random forest (RF). The results showed that terrestrial lidar data were useful for estimating maize biomass at all levels (at each level, R2 was greater than 0.80), and biomass estimation at leaf group level was the most precise (R2 = 0.97, RMSE = 2.22 g) among all four levels. All four regression techniques performed similarly at all levels. However, considering the transferability and interpretability of the model itself, SR is the suggested method for estimating maize biomass from terrestrial lidar-derived phenotypes. Moreover, height-related variables showed to be the most important and robust variables for predicting maize biomass from terrestrial lidar at all levels, and some two-dimensional variables (e.g., leaf area) and three-dimensional variables (e.g., volume) showed great potential as well. Conclusion We believe that this study is a unique effort on evaluating the capability of terrestrial lidar on estimating maize biomass at difference levels, and can provide a useful resource for the selection of the phenotypes and models required to estimate maize biomass in precision agriculture practices.

BackgroundPrevious reports have shown that short/branched chain acyl-CoA dehydrogenase (ACADSB) plays an important role in glioma, but its role in clear cell renal carcinoma (ccRCC) has not been reported.MethodsThe TIMER and UALCAN databases were used for pan-cancer analysis. RNA sequencing and microarray data of patients with ccRCC were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus database. The differential expression of ACADSB in ccRCC and normal kidney tissues was tested. Correlations between ACADSB expression and clinicopathological parameters were assessed using the Wilcoxon test. The influences of ACADSB expression and clinicopathological parameters on overall survival were assessed using Cox proportional hazards models. Gene set enrichment analysis (GSEA) was performed to explore the associated gene sets enriched in different ACADSB expression phenotypes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on genes with similar expression patterns to ACADSB. Correlations between ACADSB and ferroptosis-related genes were assessed using Spearman’s correlation analysis.ResultsPan-cancer analysis revealed that ACADSB is down-regulated in multiple cancers, and decreased expression of ACADSB correlates with poor prognosis in certain types of cancer. Differential expression analyses revealed that ACADSB was down-regulated in ccRCC, indicating that ACADSB expression could be a single significant parameter to discriminate between normal and tumor tissues. Clinical association analysis indicated that decreased ACADSB expression was associated with high tumor stage and grade. The Cox regression model indicated that low ACADSB expression was an independent risk factor for the overall survival of patients with ccRCC. GSEA showed that 10 gene sets, including fatty acid (FA) metabolism, were differentially enriched in the ACADSB high expression phenotype. GO and KEGG pathway enrichment analysis revealed that ACADSB-related genes were significantly enriched in categories related to FA metabolism, branched-chain amino acid (BCAA) metabolism, and iron regulation. Spearman’s correlation analysis suggested that the expression of ACADSB was positively correlated with the expression of ferroptosis driver genes.ConclusionsACADSB showed good diagnostic and prognostic abilities for ccRCC. The downregulation of ACADSB might promote tumorigenesis and tumor progression by inhibiting FA catabolism, BCAA catabolism, and ferroptosis in ccRCC.

In China’s fourteenth five-year plan, urban regeneration has become one of the most crucial strategies for activating the existing cities. Since creating vibrant urban spaces is a critical component of urban regeneration, understanding the patterns of community vitality helps formulate reactive regeneration policies and design interventions. However, the lack of local-scale measurement criteria and data collection methods has posed significant constraints to assessing and rejuvenating community vitality. Taking Suzhou Nanhuan New Village as a study area, our research involved a comparative study approach to investigate the fundamental driving mechanism of urban vitality with the support of a theoretical model (5D theory), multi-source data input, real-time photography technologies, and statistical analysis tools (Analytic Hierarchy Process). The result shows at the community level, the original ‘3d’ dimensions (‘Density’, ‘Diversity’, ‘Design’) remain key elements for forming vibrant spatial quality and functionality, and density factors matter significantly. This study intends to provide a new paradigm for small-scale community vitality assessment, verification, and regeneration by combining urban morphology with people-oriented and environmental-oriented perspectives. This research could support quantitative research on creating vibrant high-density communities in the urban regeneration process and bring insights to academics and design practitioners.

Landscape connectivity refers to the degree of continuity between the spatially structured units of a landscape. Ecological connectivity can characterise the degree to which ecological functional areas are connected in terms of function and ecological processes. In this study, the landscape pattern index and ecosystem service values were used to evaluate the ecological functional resistance of each landscape type, taking the Three Parallel Rivers Natural World Heritage Site as an example and the habitat distribution and population size of the Yunnan snub-nosed monkey as a reference. The minimum cost distance model, combined with the barrier impact index (BEI) and ecological connectivity index (ECI), was used to determine the degree of barrier impact on the study area and the ecological connectivity of the core reserve of the heritage site in both 2000 and 2020. The resistances of the different land types and landscape heterogeneity to the ecological function of species migration between the core protected areas of the heritage site were, in descending order, those of the forest, shrubs and grass, water, unused land, cultivated land, and built-up land. In 2020, the study area had a large BEI, with areas such as built-up areas, major roads, the sides of large rivers, and arable land being significant contributors to the blockage of landscape connectivity. The overall landscape connectivity in the study area was generally low, with clear spatial differentiation and a three-column parallel distribution pattern influenced by the topography and landscape. With the adjustment of the core reserve boundaries of the heritage site, the proportion of areas with high connectivity (ECI = 4–5) increased from 11.31% in 2000 to 34.36% in 2020. This increased landscape connectivity was conducive to the migration and reproduction of large terrestrial animals, such as the Yunnan snub-nosed monkey, with increasing numbers of populations and individuals. This study provides theoretical and methodological insights into the delineation and conservation of natural heritage sites and landscape connectivity.

The performance of real-time precise point positioning (PPP) relies primarily on the availability and quality of orbit and clock corrections. In this research, we collected data streams from 12 real-time mount points of IGS Real-Time Service (RTS) or analysis centers for a one-month period and conducted a performance assessment, including product latency and data availability, accuracy of orbit, clock and positioning performance. The epoch availability of GPS, GLONASS, Galileo and BDS was more than 98.5%, 95.79%, 94.20% and 85.9%, respectively. In addition, the orbit and clock errors of different real-time corrections was investigated. Then, PPP in static and kinematic for 16 IGS stations was conducted. The results show the real-time PPP for different products has a longer convergence time and a slightly worse accuracy than those of the post-processing PPP. For static PPP over 24 h, the real-time products of WHU had the best performance, with a mean RMSE of 1.0 cm in the horizontal and vertical directions and a median convergence time of 12.0 min. The products of CAS had the faster convergence speed due to the shortest product latency. Regarding real-time kinematic PPP for GPS only in an hourly batch, the real-time products of WHU and ESA performed best with a mean RMSE of 10.8 cm and 9.5 cm in the horizontal and vertical directions, respectively. Additionally, the PPP for different real-time products with the multi-GNSS combination obtained higher accuracy than those with GPS only in post-processing or real-time mode, and the PPP with the GPS/GLONASS/Galileo/BDS combination had the fastest convergence speed and best positioning performance. The hourly based kinematic PPP results of CAS, DLR, GFZ and WHU with the GREC combination had positioning errors smaller than 5.2 cm.

Classification of beef cuts is important for the food industry and authentication purposes. Traditional analytical methods are time constraints and incompatible with the modern food industry. Taking advantage of its rapidness and being nondestructive, multispectral imaging (MSI) has been widely applied to obtain a precise characterization of food and agriculture products. This study aims at developing a beef cut classification model using MSI and machine learning classifiers. Beef samples are imaged with a snapshot multi-spectroscopic camera within a range of 500–800 nm. In order to find a more accurate classification model, single- and multiple-modality feature sets are used to develop an accurate classification model with different machine learning-based classifiers, namely, linear discriminant analysis (LDA), support vector machine (SVM), and random forest (RF) algorithms. The results demonstrate that the optimized LDA classifier achieved a prediction accuracy of over 90% with multiple modality feature fusion. By combining machine learning and feature fusion, the other classification models also achieved a satisfying accuracy. Furthermore, this study demonstrates the potential of machine learning and feature fusion method for meat classification by using multiple spectral imaging in future agricultural applications.

Different geographical origins can lead to great variance in coffee quality, taste, and commercial value. Hence, controlling the authenticity of the origin of coffee beans is of great importance for producers and consumers worldwide. In this study, terahertz (THz) spectroscopy, combined with machine learning methods, was investigated as a fast and non-destructive method to classify the geographic origin of coffee beans, comparing it with the popular machine learning methods, including convolutional neural network (CNN), linear discriminant analysis (LDA), and support vector machine (SVM) to obtain the best model. The curse of dimensionality will cause some classification methods which are struggling to train effective models. Thus, principal component analysis (PCA) and genetic algorithm (GA) were applied for LDA and SVM to create a smaller set of features. The first nine principal components (PCs) with an accumulative contribution rate of 99.9% extracted by PCA and 21 variables selected by GA were the inputs of LDA and SVM models. The results demonstrate that the excellent classification (accuracy was 90% in a prediction set) could be achieved using a CNN method. The results also indicate variable selecting as an important step to create an accurate and robust discrimination model. The performances of LDA and SVM algorithms could be improved with spectral features extracted by PCA and GA. The GA-SVM has achieved 75% accuracy in a prediction set, while the SVM and PCA-SVM have achieved 50 and 65% accuracy, respectively. These results demonstrate that THz spectroscopy, together with machine learning methods, is an effective and satisfactory approach for classifying geographical origins of coffee beans, suggesting the techniques to tap the potential application of deep learning in the authenticity of agricultural products while expanding the application of THz spectroscopy.

C1Q (Complement 1Q) is an important recognition molecule in the immunological complement system, which could also be putatively involved in the stress responses induced by endotoxins or exotoxins, potentially through detoxification processes. Marine bivalves are well adapted to highly complex aquatic environments with various stressors. As filter feeders, they have to cope with highly potent microalgae-derived neurotoxins, such as paralytic shellfish toxin (PSTs). Zhikong scallops, Chlamys farreri, are commercially important bivalve with the remarkable ability to accumulate PSTs. Exploring the C1Qs related to PST accumulation in C. farreri could benefit our understanding of the adaptations of bivalve species. In the present study, we systematically analyzed C1Q genes in C. farreri. In total, 97 CfC1Q genes mainly from the expanded C1Q-B subfamily were identified, from which the C1QL, C1QTNF, and C1QDC1 members in C. farreri were revealed to be under positive selection. Spatiotemporal expression analysis revealed that most CfC1QLs and CfC1QDC1s were highly expressed during the post-umbo stage and in hepatopancreas, while most CfC1QTNF members were highly expressed after the creeping larva stage and in mantle. The hepatopancreas and kidney in C. farreri are two toxin-rich organs with the highest concentrations of PSTs, acting as major “centers” for toxin accumulation and transformation, respectively. Therefore, after feeding the scallops with PST-producing dinoflagellates Alexandrium minutum and Alexandrium catenella, we determined the expression patterns of CfC1Qs in these two organs. In kidney, more than 85% of CfC1QLs and CfC1QDC1s showed drastic up-regulation with both diets. However, among these members with significant induction, a different response manner was detected after feeding with A. minutum and A. catenella, respectively as acute and chronic response patterns. In comparison, far fewer CfC1Qs showing significant up-regulation in hepatopancreas with both toxic diets and only mild regulation pattern could be found. This organ-, toxin-, and time-dependent genetic regulation of CfC1Qs may contribute to the virulence difference on account of the tissue-specific or dinoflagellate-specific different toxin analogs composition, implying the possible involvement of CfC1Qs in PST transport and homeostasis. Our findings imply the functional diversity of scallop C1Q genes in coping with PST accumulation, which might be developed as potential molecular indicators for monitoring toxin accumulation in edible mollusks or provide insight into the lineage-specific adaptation of scallops for dealing with microalgal toxin challenges.

Background. Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with high mortality, and there is an urgent need of new diagnosis measures. This study is aimed at investigating whether circulating exosomal miRNAs could act as biomarkers for the diagnosis of HCC. Methods. A four-stage strategy was adopted in this study. Candidate miRNA was selected by comprehensive analysis of four GEO datasets and TCGA database. The expression of candidate miRNAs in serum exosomal samples were examined through qRT-PCR. The diagnostic utility of the final validated miRNAs was examined by receiver operating characteristic (ROC) curve analysis. Results. After synthetical analysis of four GEO datasets, six miRNAs were selected as candidates due to their higher differential fold change. miR-101 and miR-125b were selected as candidate miRNAs to further investigate their potential as biomarkers for HCC due to their differential fold change and their influence on overall survival based on the TCGA database. As a result, miR-101 and miR-125b expressions were remarkably downregulated in both tissues and serum exosomes of patients with HCC. The area under the ROC curves (AUCs) of circulating exosomal miR-101 and miR-125b were 0.894 (95% CI, 0.793–0.994) and 0.812 (95% CI, 0.675–0.950), respectively. The combination of the two miRNAs presented higher diagnostic utility for HCC (AUC=0.953). Conclusion. The exosomal miR-101 and miR-125b panel in the serum may act as a noninvasive biomarker for HCC detection.

Background Previous studies have shown that RNA Polymerase III Subunit G (POLR3G) has oncogenic effects in cultured cells and mice. However, the role of POLR3G in transitional cell carcinoma (TCC) has not been reported. This study explores the potential of POLR3G as a novel molecular marker for TCC. Methods The RNA sequencing data and clinical information of patients with TCC were downloaded from The Cancer Genome Atlas official website. Transcriptome analysis was performed as implemented in the edgeR package to explore whether POLR3G was up-regulated in TCC tissues compared to normal bladder tissues. The expression of POLR3G in bladder cancer cell line T24 and human uroepithelial cell line SV-HUC-1 were detected via quantitative real time polymerase chain reaction (qRT-PCR). Correlations between POLR3G expression and clinicopathological characteristics were analyzed using Mann-Whitney U test or Kruskal-Wallis H test. Clinicopathological characteristics associated with overall survival were explored using the Kaplan-Meier method and Cox regression analyses. Gene set enrichment analysis (GSEA) was performed to explore the associated gene sets enriched in different POLR3G expression phenotypes and the online tool Tumor IMmune Estimation Resource (TIMER) was used to explore the correlation between POLR3G expression and tumor immune infiltration in TCC. Results Transcriptome analysis showed that POLR3G was significantly up-regulated in TCC tissues compared to normal bladder tissues. Furthermore, qRT-PCR revealed high expression of POLR3G in T24 cells compared to SV-HUC-1 cells. Overall, POLR3G expression was associated with race, tumor status, tumor subtype, T classification, and pathological stage. Kaplan-Meier survival analysis revealed that higher POLR3G expression was associated with lower overall survival. The univariate Cox regression model revealed that age at diagnosis, pathological stage, and POLR3G expression were associated with prognosis of TCC patients. Further multivariate analyses identified these three clinicopathological characteristics as independent prognostic factors for overall survival. GSEA analysis showed that several gene sets associated with tumor development and metastasis, including TGF-β signaling, PI3K-AKT-mTOR signaling, and IL6-JAK-STAT3 signaling, were significantly enriched in POLR3G high expression phenotype. Immune infiltration analysis revealed that the expression of POLR3G was significantly correlated with infiltrating levels of immune cells, including CD8+ T cells, neutrophils, and dendritic cells; and the expression of POLR3G was also significantly correlated with the expression of immune checkpoint molecules, such as PD1, PD-L1, PD-L2, CTLA4, LAG3, HAVCR2, and TIGIT. Conclusions POLR3G was up-regulated in TCC and high POLR3G expression correlated with poor prognosis. POLR3G can potentially be used as a prognostic marker for TCC and might be of great value in predicting the response to immunotherapy.

In this study, the phenomenon of gas removal behaviors in the melt pool and the flow behaviors of melt pool were observed using an in-situ X-ray imaging method. Based on the ultrasonic effects, a novel processing method was developed to reduce porosity and decrease diffusible hydrogen content in the deposited metal. The effects of ultrasonic output power on the size and frequency of gas bubble collapsing were studied. Results showed that with the assistance of ultrasonic, the gas bubble size were smaller and the collapsing frequency was significantly increased. The porosity decreased from 1.4% to 0.5% and the hydrogen diffusible content decreased from 24.5 to 18.6 ml/100 g when the ultrasonic power increased to 720 W. The possible hydrogen removal mechanism was proposed by two aspects including the microcosmic and macrocosmic scale. Keywords: Underwater welding, Ultrasonic melt processing, Solidification, Diffusible hydrogen, In-situ X-ray imaging

The grain orientation of Sn-based solder joints on copper pillars under the combined action of electron wind force and temperature gradient greatly affects their electromigration damage. The copper pillars with Sn-1.8Ag lead-free solder on the top was subjected to a current density of 1.5 × 104 A/cm2 at 125 °C to study the electromigration behaviors. The grain orientation was characterized by scanning electron microscopy (SEM) equipped with electron backscattered diffraction (EBSD) detector. Metal dissolution and voids formation in the cathode as well as massive intermetallic compounds(IMC) accumulation in the anode were observed after electromigration. Closer examination of solder joints revealed that the Sn grain whose c-axis perpendicular to electric current may have retarded Cu diffusion to anode and IMC accumulation. In addition, the newly formed Cu6Sn5 exhibited preferred orientation related to the electric current direction.

Satellite laser ranging (SLR) observations provide an independent validation of the global navigation satellite system (GNSS) orbits derived using microwave measurements. SLR residuals have also proven to be an important indicator of orbit radial accuracy. In this study, SLR validation is conducted for the precise orbits of eight Galileo satellites covering four to eight years (the current longest span), provided by multiple analysis centers (ACs) participating in the multi-GNSS experiment (MGEX). The purpose of this long-term analysis (the longest such study to date), is to provide a comprehensive evaluation of orbit product quality, its influencing factors, and the effect of perturbation model updates on precise orbit determination (POD) processing. A conventional ECOM solar radiation pressure (SRP) model was used for POD. The results showed distinct periodic variations with angular arguments in the SRP model, implying certain defects in the ECOM system. Updated SRP descriptions, such as ECOM2 or the Box-Wing model, led to significant improvements in SLR residuals for orbital products from multiple ACs. The standard deviation of these residuals decreased from 8–10 cm, before the SRP update, to about 3 cm afterward. The systematic bias of the residuals was also reduced by 2–4 cm and the apparent variability decreased significantly. In addition, the effects of gradual SRP model updates in the POD were evident in orbit comparisons. Orbital differences between ACs in the radial direction were reduced from the initial 10 cm to better than 3 cm, which is consistent with the results of SLR residual analysis. These results suggest SLR validation to be a powerful technique for evaluating the quality of POD strategies in GNSS orbits. Furthermore, this study has demonstrated that perturbation models, such as SRP, provide a better orbit modeling for the Galileo satellites.

Prostate cancer (PCa), especially metastatic PCa, is one of the main cancer types accounting for male mortality worldwide. Over decades, researchers have tried to search for effective curative methods for PCa, but many attempts have failed. The therapeutic failure of PCa is usually due to off-target or side effects; thus, finding a key molecule that could prevent PCa metastatic progression has become the most important goal for curing aggressive PCa. In this study, we collected hundreds of PCa tissues and serum and urine samples from patients to verify the upregulated expression of PC3-secreted microprotein (PSMP) in PCa tumor tissues with high Gleason scores. According to biopsy results, PSMP expression was found related to extraprostatic extension (EPE), contributing to PCa metastasis. Mechanistically, recombinant PSMP protein could promote the proliferation both in vitro and in vivo, and rhPSMP could promote epithelial–mesenchymal transition (EMT) of PC3 in vitro. Additionally, PSMP could also influence cytokine production in the xenograft model and monocyte migration and macrophage polarization in vitro. Our most important finding was that neutralizing antibodies against PSMP could suppress xenograft PC3 growth and promote the survival of PC3 metastatic mice model, providing an effective option to cure human PCa.