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Abstract Background The excavation and utilization of endophytic fungi from medicinal plants is highly important for the development of new drugs. The endophytic fungus Aspergillus tamarii TPD11, which was isolated and obtained by the authors in the previous stage, can produce a variety of polyphyllins with important potential applications in hemostasis, inflammation and antitumor activities; however, the genomic information of TPD11 is still unknown. Results In this study, we sequenced and assembled the whole genome of the endophytic fungus A. tamarii TPD11, resolved the genome evolutionary relationships of 24 Aspergillus strains, and phylogenetic analysis of the genomes of 16 strains revealed the evolutionary differences between Aspergillus and Penicillium and the mechanisms of genome expansion and contraction. CAZy annotation analysis revealed that TPD11 obtains nutrients mainly by ingesting starch from the host plant. TPD11 has a biosynthesis-related gene cluster for the synthesis of squalestatin S1, and the silencing of this biosynthesis-related gene cluster might increase the content of polyphyllin. Annotation of 11 UDP-glycosyltransferase genes helps to further reveal the biosynthetic pathway of polyphyllin. In addition, secondary metabolism gene cluster and CAZy analyses confirmed the potential probiotic, insecticidal and antimicrobial activities of TPD11 on host plants. Conclusions This study reveals the intrinsic mechanism by which endophytic fungi increase the content of polyphyllin, which provides a basis for the synthetic synthesis of the natural product polyphyllin.

Abstract Lymph node metastasis (LNM) is a typical marker in oral squamous cell carcinoma (OSCC) indicating poor prognosis. Pathological examination by artificial image acquisition and analysis, as the main diagnostic method for LNM, often takes a week or longer which may cause great anxiety of the patient and also retard timely treatment. However, there are few efficient fast LNM diagnosis methods in clinical applications currently. Our previous study profiled the proteomics of extracellular vesicles (EVs) derived from postoperative drainage fluid (PDF) and showed the potential of detecting specific EVs that expressed aspartate β-hydroxylase (ASPH) for LNM diagnosis in OSCC patients. Considering that the analysis of ASPH+ PDF-EVs is challenging due to their low abundance (counting less than 10% of total EVs in PDF) and the complex EV isolation process of ultra-centrifugation, we developed a facile platform containing two microfluidic chips filled with antibody-modified microbeads to isolate ASPH+ PDF-EVs, with both the capture and retrieval rate reaching around 90%. Clinical sample analysis based on our method revealed that a mean of 6 × 106 /mL ASPH+ PDF-EVs could be isolated from LNM+ OSCC patients compared to 2.5 × 106 /mL in LNM- OSCC ones. When combined with enzyme-linked immunosorbent assay (ELISA) technique that was commonly used in clinical laboratories in hospitals, this microfluidic platform could precisely distinguish postoperative OSCC patients with LNM or not in several hours, which were validated by a double-blind test containing 6 OSCC patients. We believe this strategy has promise for early diagnosis of LNM in postoperative OSCC patients and finally helps guiding timely and reasonable treatment in clinic.

Abstract Semantic image synthesis approaches has been dominated by the modelling of Convolutional Neural Networks (CNN). Due to the limitations of local perception, their performance improvement seems to have plateaued in recent years. To tackle this issue, we propose the SC-UNet model, which is a UNet-like network fused Swin Transformer and CNN for semantic image synthesis. Photorealistic image synthesis conditional on the given semantic layout depends on the high-level semantics and the low-level positions. To improve the synthesis performance, we design a novel conditional residual fusion module for the model decoder to efficiently fuse the hierarchical feature maps extracted at different scales. Moreover, this module combines the opposition-based learning mechanism and the weight assignment mechanism for enhancing and attending the semantic information. Compared to pure CNN-based models, our SC-UNet combines the local and global perceptions to better extract high- and low-level features and better fuse multi-scale features. We have conducted an extensive amount of comparison experiments, both in quantitative and qualitative terms, to validate the effectiveness of our proposed SC-UNet model for semantic image synthesis. The outcomes illustrate that SC-UNet distinctively outperforms the state-of-the-art model on three benchmark datasets (Citysacpes, ADE20K, and COCO-Stuff) including numerous real-scene images.

Highlights MIL-88C (Fe) with varying aspect ratios as a precursor was synthesized by regulating oil bath conditions, followed by one-step thermal decomposition to obtain carbon-coated iron-based composites. High-efficiency microwave absorption properties were achieved with RL min value of -67.4 dB (2.13 mm) and wide effective absorption bandwidth (EAB) of 5.52 GHz (1.90 mm) under the low filler loading. A symmetric gradient honeycomb structure was constructed utilizing the high-frequency structure simulator, achieving an EAB of 14.6 GHz and a RL min of -59.0 dB.

Abstract Dental, oral, and craniofacial diseases jeopardize health and reduce the quality of life. Accessing disease-related signals in advance is beneficial to prevent the occurrence or progression of those diseases. However, the inconvenience of periodical in-hospital examinations and the difficulty of sustaining daily health monitoring challenge personal compliance and possibly lead to limited prevention or treatment. Medical flexible electronics are electric devices fabricated on soft and extensible substrates to fit the human skin and enable non-invasive continuous monitoring of biophysical/biochemical signals. They provide the possibility of long-term, continuous, comfortable, and wireless healthcare monitoring and are expected to alleviate time and economic consumption by avoiding in-hospital examinations and treatment. Therefore, flexible electronics have emerged for early diagnosis and disease monitoring in stomatology. It is noteworthy that special biophysical/biochemical characteristics and the environment of dental, oral, and craniofacial areas bring distinct challenges that flexible electronics need to address ingeniously to ensure their stability, selectivity, and sensitivity. This review summaries flexible electronics and their specificity when used in dental, oral, and craniofacial applications, including monitoring saliva or cavity-gas related biosignals, sensing the mechanical fluctuation from facial muscle/respiratory activities or orthodontic forces, and executing special functions in the prevention or postoperative recovery of relevant diseases. Furthermore, after analyzing current challenges and proposing potential solutions, the “5I” principles of imperceptibility, intelligence, individualization, integration, and inexpensiveness are presented to help guide the future development of flexible electronics and promote their commercialization for dental, oral, and craniofacial medicine.

Abstract Improving the absorption of electromagnetic waves at low-frequency bands (2-8 GHz) is crucial for the increasing electromagnetic (EM) pollution brought about by the innovation of the fifth generation (5G) communication technology. However, the poor impedance matching and intrinsic attenuation of material in low-frequency bands hinders the development of low-frequency electromagnetic wave absorbing (EMWA) materials. Here we propose an interface-induced dual-pinning mechanism and establish a magnetoelectric bias interface by constructing bilayer core-shell structures of NiFe2O4 (NFO)@BiFeO3 (BFO)@polypyrrole (PPy). Such heterogeneous interface could induce distinct magnetic pinning of the magnetic moment in the ferromagnetic NFO and dielectric pinning of the dipole rotation in PPy. The establishment of the dual-pinning effect resulted in optimized impedance and enhanced attenuation at low-frequency bands, leading to better EMWA performance. The minimum reflection loss (RLmin) at thickness of 4.43 mm reaches -65.30 dB (the optimal absorption efficiency of 99.99997%), and the effective absorption bandwidth (EAB) can almost cover C-band (4.72 ~ 7.04 GHz) with low filling of 15.0 wt.%. This work proposes a mechanism to optimize low-frequency impedance matching with electromagnetic wave (EMW) loss and pave an avenue for the research of high-performance low-frequency absorbers.

Abstract Background The intriguing connection between selenium and cancer resembles a captivating puzzle that keeps researchers engaged and curious. While selenium has shown promise in reducing cancer risks through supplementation, its interaction with epigenetics in cervical cancer remains a fascinating yet largely unexplored realm. Unraveling the intricacies of selenium's role and its interaction with epigenetic factors could unlock valuable insights in the battle against this complex disease. Result Selenium has shown remarkable inhibitory effects on cervical cancer cells in various ways. In in vitro studies, it effectively inhibits the proliferation, migration, and invasion of cervical cancer cells, while promoting apoptosis. Selenium also demonstrates significant inhibitory effects on human cervical cancer-derived organoids. Furthermore, in an in vivo study, the administration of selenium dioxide solution effectively suppresses the growth of cervical cancer tumors in mice. One of the mechanisms behind selenium's inhibitory effects is its ability to inhibit histone demethylases, specifically JMJD3 and UTX. This inhibition is observed both in vitro and in vivo. Notably, when JMJD3 and UTX are inhibited with GSK-J4, similar biological effects are observed in both in vitro and in vivo models, effectively inhibiting organoid models derived from cervical cancer patients. Inhibiting JMJD3 and UTX also induces G2/M phase arrest, promotes cellular apoptosis, and reverses epithelial-mesenchymal transition (EMT). ChIP-qPCR analysis confirms that JMJD3 and UTX inhibition increases the recruitment of a specific histone modification, H3K27me3, to the transcription start sites (TSS) of target genes in cervical cancer cells (HeLa and SiHa cells). Furthermore, the expressions of JMJD3 and UTX are found to be significantly higher in cervical cancer tissues compared to adjacent normal cervical tissues, suggesting their potential as therapeutic targets. Conclusions Our study highlights the significant inhibitory effects of selenium on the growth, migration, and invasion of cervical cancer cells, promoting apoptosis and displaying promising potential as a therapeutic agent. We identified the histone demethylases JMJD3 and UTX as specific targets of selenium, and their inhibition replicates the observed effects on cancer cell behavior. These findings suggest that JMJD3 and UTX could be valuable targets for selenium-based treatments of cervical cancer.

Incorporation of steel fibers to improve the defects of manufactured sand concrete (MSC) has received a great deal of attention, while the fracture mechanism of the MSC by volume fraction of steel fibers (Vf) has been less studied. To investigate the effects of steel fibers on the fracture characteristics of the MSC, three-point bending tests were conducted on the MSC beams with different Vf (0, 0.5 %, 1.0 % and 1.5 %) using digital image correlation technique. The effects of Vf on the fracture parameters and crack propagation paths of steel fiber reinforced manufactured sand concrete (SFRMSC) were analyzed. In addition, fracture process zone (FPZ) of the SFRMSC was analyzed via the length of the FPZ (lFPZ) and area of the FPZ (AFPZ). The results indicated that the residual strength, initiation fracture toughness, unstable fracture toughness, fracture energy and characteristic length of the SFRMSC increased with the increase of Vf, whereas the crack propagation paths were not sensitive to the changes of Vf. The addition of steel fibers increased the interaction between the aggregate and the matrix, which led to an increase in the number of microcracks. Before approaching the Pc, both the lFPZ and AFPZ showed essentially stable changes. As Vf increased, the lFPZ and AFPZ developed faster to their corresponding maximum values. The AFPZ reached a maximum and increased with the Vf. At the Pc, the lFPZ and AFPZ changed in a similar trend when Vf ≤ 1.0 %. When Vf > 1.0 %, the lFPZ changed slightly while the AFPZ increases sharply.

Cartilage regeneration remains difficult due to a lack of blood vessels. Degradation of the extracellular matrix (ECM) causes cartilage defects, and the ECM provides the natural environment and nutrition for cartilage regeneration. Until now, collagen hydrogels are considered to be excellent material for cartilage regeneration due to the similar structure to ECM and good biocompatibility. However, collagen hydrogels also have several drawbacks, such as low mechanical strength, limited ability to induce stem cell differentiation, and rapid degradation. Thus, there is a demanding need to optimize collagen hydrogels for cartilage regeneration. In this review, we will first briefly introduce the structure of articular cartilage and cartilage defect classification and collagen, then provide an overview of the progress made in research on collagen hydrogels with chondrocytes or stem cells, comprehensively expound the research progress and clinical applications of collagen‐based hydrogels that integrate inorganic or organic materials, and finally present challenges for further clinical translation.

Calotes wangi sp. nov., a new species of the agamid genus Calotes Cuvier, 1817, from southern China and northern Vietnam, is described. This species can be distinguished from all known congeners by a combination of morphological characteristics and genetic divergence in the mitochondrial tRNA, ND2, and CO1 genes. Molecular phylogenetic analysis revealed that the new species was formed as a monophyletic group and that considerable genetic divergence existed between its congeners (minimum p-distance, 4.6%). Calotes wangi sp. nov. is distinguished by a combination of the following characteristics: average SVL < 90 mm for adult males; 10–14 dorsal eyelid scales; scales on side of neck and adjacent shoulder area pointing obliquely upward; keels on neck scales weakly to strongly developed; fold in front of the shoulder absent; pair of dark triangular patches extending from the front of the shoulder to the jaw angles; and orange coloration of the tongue. Calotes wangi sp. nov. is similar to C. irawadi but differs in having scales between the nasal shield and the orbit and a fourth toe with a claw that can reach between the eyes and tympanum (even to the snout when hind the limbs are adpressed forward). Phylogenetic analyses revealed two well-supported subspecies, Lineages A and B in C. wangi sp. nov., with mean uncorrected p-distances between them of 2%. We propose that Lineage A, which is mainly from the central and southern Wuzhi Mountains on Hainan Island, is a subspecies, C. w. hainanensis ssp. nov. Lineage B mainly comprises individuals from other sites on the island plus the adjacent mainland, and is described as subspecies, C. w. wangi ssp. nov. A diagnostic key to all Calotes species of China is also provided.

AIM: To investigate the efficacy of epithelial-off accelerated corneal cross-linking(CXL)in the treatment of advanced keratoconus.METHODS: A retrospective study was performed on data collected from 32 patients(43 eyes)with advanced keratoconus who underwent epithelial-off accelerated CXL at Ningxia Eye Hospital from April 2020 to December 2021. Slit-lamp, intraocular pressure, uncorrected visual acuity(UCVA), corrected visual acuity, specular microscope, Pentacam and Corvis ST were tested before and at 1, 3 and 6mo after surgery. Preoperative and postoperative corneal condition, UCVA, best corrected visual acuity(BCVA)and the values of corneal endothelial, maximum keratometry(Kmax), thinnest corneal thickness(TCT), anterior and posterior surfaces of the cornea K1, K2, biomechanically corrected intraocular pressure(bIOP), applanation time 1(A1T), applanation length 1(A1L), applanation velocity 1(A1V), applanation time 2(A2T), applanation length 2(A2L), applanation velocity 2(A2V), highest concavity deformation amplitude(HCDA), radius at highest curvature(HCR), highest concavity peak distance(HCPD)and stiffness parameter at first applanation(SP-A1)were recorded.RESULTS: There were differences between UCVA(LogMAR; 1.06±0.49, 0.78±0.39)and BCVA(LogMAR; 0.48±0.34, 0.38±0.29)before and at 6mo after surgery(P0.05).CONCLUSION: Epithelial-off accelerated CXL can prevent the progression of keratoconus within half year after surgery, and it has certain safety.

Abstract Biochar is a potential porous carbon to remove the contaminants from aquatic environments. Herein, N-doped hierarchical biochar was produced by the combined approach of ammonia torrefaction pretreatment (ATP) and alkali activation. ATP could not only incorporate N element into poplar wood, but obtain the loose structure of poplar wood. The highest surface area of N-doped hierarchical biochar was 2324.61 m2 g−1 after ammonia wet torrefaction pretreatment, which was higher than that of activation carbon (1401.82 m2 g−1) without torrefaction pretreatment, the hierarchical biochar (2111.03 m2 g−1) without ammonia atmosphere. The N-doped hierarchical biochar presented the highest adsorption capacity (564.7 mg g−1) of methyl orange (MO), which was 14.64-fold of that on biochar without N doping. In addition, the pseudo-second-order and Langmuir model fitted well with the adsorption kinetics and isotherms of the N-doped hierarchical biochar. The incorporation of nitrogen element could not only tune the distribution of surface electrons on biochar, but optimize the ambient condition of adsorption active sites as well. The adsorption of MO might occur on the N-/O-containing functional groups through the electrostatic interaction, the π-π dispersion interaction, and the hydrogen bonding. The density functional theory showed that the graphitic-N and pyridinic-N were the dominant adsorption active sites. Graphical Abstract

Abstract Background The use of health technologies and gamification to promote physical activity has increasingly been examined, representing an opportunistic method for harnessing social support inherent within existing social ties. However, these prior studies have yielded mixed findings and lacked long-term follow-up periods. Thus, a pilot cluster randomized controlled trial was conducted to gauge the feasibility and preliminary efficacy of a digital gamification-based physical activity promotion approach among teams of insufficiently active adults with existing social ties. Methods Teams (N = 24; 116 total participants) were randomized to either a 12-week intervention (Fitbit, step goals, app, feedback; TECH) or the same program plus gamification (TECH + Gamification). Mixed effects models were used to compare group differences in treatment adherence, and changes in social support, steps, and moderate-to-vigorous physical activity at 12 weeks and 52 weeks from baseline, adjusted for sociodemographic characteristics and team size. Results TECH had a lower mean number of days of Fitbit self-monitoring versus TECH + Gamification during the intervention (adjusted difference: -.30; 95% CI, -.54 to -.07; P = .01). Post-intervention, TECH had 47% lower odds of self-monitoring 7 days per week versus TECH + Gamification (.53; 95% CI, .31 to .89; P = .02). No differences were observed between TECH + Gamification and TECH in increases in social support (0.04; 95% CI, -.21 to .29; P = .76), ActiGraph-measured daily steps (-425; 95% CI, -1065 to 215; P = .19), or moderate-to-vigorous physical activity minutes (-3.36; 95% CI, -8.62 to 1.91; P = .21) from baseline to 12 weeks or in the regression of these improvements by 1 year (Ps > .05). Although not significant in the adjusted models (Ps > .05), clinically meaningful differences in Fitbit-measured daily steps (TECH, 7041 ± 2520; TECH + Gamification, 7988 ± 2707) and active minutes (TECH, 29.90 ± 29.76; TECH + Gamification, 36.38 ± 29.83) were found during the intervention. Conclusions A gamified physical activity intervention targeting teams of adults with existing social ties was feasible and facilitated favorable, clinically meaningful additive physical activity effects while in place but did not drive enhanced, long-term physical activity participation. Future investigations should explore optimal team dynamics and more direct ways of leveraging social support (training teams; gamifying social support). Trial registration Clinicaltrials.gov ( NCT03509129 , April 26, 2018).

The Malayan Banded Wolf Snake Lycodon subcinctus Boie, 1827 once included three subspecies, namely L. s. subcinctus Boie, 1827, L. s. sealei Leviton, 1955, and L. s. maculatus (Cope, 1985). Thereafter, L. s. sealei has been elevated to species level, and the taxonomic status of L. s. maculatus has not been resolved. We sequenced the mitochondrial cytochrome b (cytb) gene fragments of eight specimens of L. s. maculatus from China, including three from the adjacent areas of its type locality. Combining the sequences obtained from GenBank, we reconstructed a molecular phylogeny and reevaluated the taxonomic status of L. s. maculatus. Phylogenetic analysis revealed three highly divergent lineages within L. subcinctus sensu lato which correspond to L. subcinctus sensu stricto, L. sealei, and L. s. maculatus, respectively. Coupled with morphological comparison, we elevate L. s. maculatus to full species and redescribe it based on the type and freshly collected material.

Abstract Background Familial exudative vitreoretinopathy (FEVR) is a genetic eye disorder that leads to abnormal development of retinal blood vessels, resulting in vision impairment. This study aims to identify pathogenic variants by targeted exome sequencing in 9 independent pedigrees with FEVR and characterize the novel pathogenic variants by molecular dynamics simulation. Methods Clinical data were collected from 9 families with FEVR. The causative genes were screened by targeted next-generation sequencing (TGS) and verified by Sanger sequencing. In silico analyses (SIFT, Polyphen2, Revel, MutationTaster, and GERP + +) were carried out to evaluate the pathogenicity of the variants. Molecular dynamics was simulated to predict protein conformation and flexibility transformation alterations on pathogenesis. Furthermore, molecular docking techniques were employed to explore the interactions and binding properties between LRP5 and DKK1 proteins relevant to the disease. Results A 44% overall detection rate was achieved with four variants including c.4289delC: p.Pro1431Argfs*8, c.2073G > T: p.Trp691Cys, c.1801G > A: p.Gly601Arg in LRP5 and c.633 T > A: p.Tyr211* in TSPAN12 in 4 unrelated probands. Based on in silico analysis and ACMG standard, two of them, c.4289delC: p.Pro1431Argfs*8 and c.2073G > T: p.Trp691Cys of LRP5 were identified as novel pathogenic variants. Based on computational predictions using molecular dynamics simulations and molecular docking, there are indications that these two variants might lead to alterations in the secondary structure and spatial conformation of the protein, potentially impacting its rigidity and flexibility. Furthermore, these pathogenic variants are speculated to potentially influence hydrogen bonding interactions and could result in an increased binding affinity with the DKK1 protein. Conclusions Two novel genetic variants of the LRP5 gene were identified, expanding the range of mutations associated with FEVR. Through molecular dynamics simulations and molecular docking, the potential impact of these variants on protein structure and their interactions with the DKK1 protein has been explored. These findings provide further support for the involvement of these variants in the pathogenesis of the disease.

Abstract The surface color of cigar tobacco leaves (CTLs) is largely determined by the browning response and is one of the most important quality traits affecting consumer preferences. The physiological changes and metabolic network of browning in CTLs after harvest have not been reported. We investigated the molecular mechanism of browning in CTLs by comparing the physiological characteristics and metabolites of CTLs browning at five postharvest periods. Phenotypic traits and browning-related enzyme activity data indicated that the browning reaction was most intense at approximately 12 d when polyphenol oxidase and peroxidase activities reached their maximum. Postharvest CTLs polyphenols, polyacids, and carbon and nitrogen compounds were rapidly degraded during the yellowing phase, and the biosynthesis rate of polyphenols and carotenoids was greater than the degradation rate during the browning phase. Metabolomic analysis discovered 2027 metabolites that were annotated mainly to lipids and lipid-like molecules, organic acids and their derivatives, and organic heterocyclic components. Hierarchical cluster analysis discovered glutamate, serine, threonine, ornithine, and arginine as the major amino acids involved in the browning reaction. KEGG pathway enrichment analysis indicated that the metabolic pathways with important effects on enzymatic browning were phenylpropanoid biosynthesis, flavonoid biosynthesis, isoquinoline alkaloid biosynthesis, phenylalanine metabolism, and linoleic acid metabolism. The metabolic pathway network was mined, and the main polyphenols involved in the browning reaction of CTLs were found to be cyanidin, rutin, caffeoylquinic acid, kaempferol, naringin, and neohesperidin. This study provides a reference for the browning physiology and metabolism network of postharvest CTLs. Graphical Abstract

Abstract Graphical user interfaces (GUIs) are widely used in human–computer interaction, providing a convenient interface for operation. Automating the conversion of GUI design images into source code can significantly reduce the coding workload for front-end developers. Detecting elements in GUI images is a key challenge in achieving automatic GUI code generation and is crucial for tasks such as GUI automation and testing. However, current state-of-the-art methods do not fully consider the unique characteristics of GUI images and elements, and they lack the required high localization accuracy, resulting in low detection accuracy for GUI element boxes. In this paper, we propose GUICG, an automatic GUI code generator that combines deep neural networks with image processing techniques to efficiently detect GUI elements from GUI images and generate front-end code. We empirically investigate various deep learning approaches and image processing methods for GUI component detection. Based on a comprehensive understanding of their performance and characteristics, we design GUICG by fusing image processing with a deep learning-based target detection model, achieving state-of-the-art performance. GUICG outperforms existing methods in accuracy and F1 score for component detection tasks, while producing human-readable code with a logical structure. Furthermore, we conduct an ablation study to quantitatively assess the impact of each key element in GUICG.

AIM:To evaluate the changes in corneal biomechanics of patients with moderate refractive error after receiving small-incision lenticule extraction(SMILE)and femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)using the corneal visualization Scheimpflug technology(Corvis ST).METHODS:Prospective cohort study. A total of 65 moderate myopia patients(65 eyes)who were scheduled to undergo refractive surgery at the Ophthalmic Refractive Surgery Center of the Ningxia Eye Hospital from November 2020 to November 2021 were included in the study, and there were 30 eyes in the SMILE group and 35 eyes in the FS-LASIK group. The changes in corneal biomechanical parameters, including integrated radius(IR), inverse concave radius(ICR), deformation amplitude ratio 2mm(DAR2), stiffness parameter at first applanation(SP-A1), ambrosio relational thickness(ARTh)and the central curvature radius at highest concavity(HC-Radius)were observed by Corvis ST between both groups preoperatively and 1 and 3mo postoperatively.RESULTS: There were no statistical significance in biomechanical parameters between two groups of patients 1 and 3mo postoperatively(P>0.05). IR, ICR and DAR2 of each groups of patients 1 and 3mo postoperatively were significantly increased than those preoperatively, and SP-A1, ARTh and HC-Radius were significantly decreased than those preoperatively(all P0.05). In addition, a positive correlation was found between central corneal thickness(CCT)and ARTh and SP-A1 of the two groups of patients at 3mo postoperatively(FS-LASIK group: r=0.727, 0.819, SMLIE group: r=0.683, 0.434, all P

Transitioning fundamental and applied science to evidence-based real-world applications is challenging yet necessary, especially in environmental sciences. In this paper, a quantitative data analysis method is presented to support decision-making by augmenting qualitative customer discover methods used for new technology adoption. This method can be used to assess: i) customer segment (CS) and value proposition (VP) validity and ii) the ability of a new technology to address the VP. Two different environmental technologies were evaluated to demonstrate this quantitative approach. CS and VP(s) that were previously qualitatively identified were statistically (in)validated using binomial testing. In each of the presented cases, the CS was statistically validated but only one of the three VPs for each case was validated. The validated performance parameters for each technologywere tested against cost and performance data using linear optimization. This testing allowed for the identification of conditions under which the technology met minimum customer performance requirements and where further data or technology modifications were still needed. These identified conditions establish the features necessary to transition the technologies to the minimum viable product (MVP) phase of commercialization. One technology was found to be ready for MVP development while the other technology needed additional data and modification. Both findings demonstrate the effectiveness of this quantitative data analysis method and guide decision-making in the early stages of technology commercialization.

Osteosarcoma (OS) is the most common primary malignant bone tumor. In the clinic, usual strategies for OS treatment include surgery, chemotherapy, and radiation. However, all of these therapies have complications that cannot be ignored. Therefore, the search for better OS treatments is urgent. Black phosphorus (BP), a rising star of 2D inorganic nanoparticles, has shown excellent results in OS therapy due to its outstanding photothermal, photodynamic, biodegradable and biocompatible properties. This review aims to present current advances in the use of BP nanoparticles in OS therapy, including the synthesis of BP nanoparticles, properties of BP nanoparticles, types of BP nanoparticles, and modification strategies for BP nanoparticles. In addition, we have discussed comprehensively the application of BP in OS therapy, including single, dual, and multimodal synergistic OS therapies, as well as studies about bone regeneration and antibacterial properties. Finally, we have summarized the conclusions, limitations and perspectives of BP nanoparticles for OS therapy.

Introduction: There is clinical evidence that the fresh blood viscosity is an important indicator in the development of vascular disorder and coagulation. However, existing clinical viscosity measurement techniques lack the ability to measure blood viscosity and replicate the in-vivo hemodynamics simultaneously.Methods: Here, we fabricate a novel digital device, called Tesla valves and ultrasound waves-powered blood plasma viscometer (TUBPV) which shows capacities in both viscosity measurement and coagulation monitoring.Results: Based on the Hagen-Poiseuille equation, viscosity analysis can be faithfully performed by a video microscopy. Tesla-like channel ensured unidirectional liquid motion with stable pressure driven that was triggered by the interaction of Tesla valve structure and ultrasound waves. In few seconds the TUBPV can generate an accurate viscosity profile on clinic fresh blood samples from the flow time evaluation. Besides, Tesla-inspired microchannels can be used in the real-time coagulation monitoring.Discussion: These results indicate that the TUBVP can serve as a point-of-care device in the ICU to evaluate the blood’s viscosity and the anticoagulation treatment.

The shale oil and gas exploitation in China is technically benchmarked with the United States in terms of development philosophy, reservoir stimulation treatment, fracturing parameters, fracturing equipment and materials, oil/gas production technology, and data/achievements sharing. It is recognized that the shale oil and gas exploitation in China is weak in seven aspects: understanding of flow regimes, producing of oil/gas reserves, monitoring of complex fractures, repeated stimulation technology, oil/gas production technology, casing deformation prevention technology, and wellbore maintenance technology. Combined with the geological and engineering factors of shale oil and gas in China, the development suggestions of four projects are proposed from the macro- and micro-perspective, namely, basic innovation project, exploitation technology project, oil/gas production stabilization project, and supporting efficiency-improvement project, so as to promote the rapid, efficient, stable, green and extensive development of shale oil and gas industry chain and innovation chain and ultimately achieve the goal of “oil volume stabilizing and gas volume increasing”.

A new species of armored scale insect, Aulacaspis fanjingshanensis sp. nov. is described and illustrated based on adult female specimens collected on Rosaceae plants in China. A key to the Aulacaspis species known from Guizhou Province of China is provided. Our molecular study suggests that Aulacaspis schizosoma (Takagi, 1970) is not a true member of the genus Aulacaspis; the genus Superturmaspis Chen, 1983 is revived and A. schizosoma is transferred to it as Superturmaspis schizosoma (Takagi, 1970), revived combination, based on a molecular phylogeny.

DNA barcoding is used to identify cryptic species, survey environmental samples, and estimate phyletic and genetic diversity. Armored scale insects are phytophagous insects and are the most species-rich taxa in the Coccoidea superfamily. This study developed a DNA barcode library for armored scale insect species collected from southern China during 2021-2022. We sequenced a total of 239 specimens, recognized as 50 morphological species, representing two subfamilies and 21 genera. Sequencing analysis revealed that the average G + C content of the cytochrome oxidase subunit I (COI) gene sequence was very low (~18.06%) and that the average interspecific divergence was 10.07% while intraspecific divergence was 3.20%. The intraspecific divergence value was inflated by the high intraspecific divergence in ten taxa, which may indicate novel species overlooked by current taxonomic treatments. All the Automated Barcode Gap Discovery, Assemble Species by Automatic Partitioning, Taxon DNA analysis and Bayesian Poisson Tree Process methods yielded largely consistent results, indicating a robust and credible species delimitation. Based on these results, an intergeneric distance threshold of ≤ 5% was deemed appropriate for the differentiation of armored scale insect species in China. This study establishes a comprehensive barcode library for the identification of armored scale insects, future research, and application.

Introduction Traditional survey-based surveillance is costly, limited in its ability to distinguish diabetes types and time-consuming, resulting in reporting delays. The Diabetes in Children, Adolescents and Young Adults (DiCAYA) Network seeks to advance diabetes surveillance efforts in youth and young adults through the use of large-volume electronic health record (EHR) data. The network has two primary aims, namely: (1) to refine and validate EHR-based computable phenotype algorithms for accurate identification of type 1 and type 2 diabetes among youth and young adults and (2) to estimate the incidence and prevalence of type 1 and type 2 diabetes among youth and young adults and trends therein. The network aims to augment diabetes surveillance capacity in the USA and assess performance of EHR-based surveillance. This paper describes the DiCAYA Network and how these aims will be achieved.Methods and analysis The DiCAYA Network is spread across eight geographically diverse US-based centres and a coordinating centre. Three centres conduct diabetes surveillance in youth aged 0–17 years only (component A), three centres conduct surveillance in young adults aged 18–44 years only (component B) and two centres conduct surveillance in components A and B. The network will assess the validity of computable phenotype definitions to determine diabetes status and type based on sensitivity, specificity, positive predictive value and negative predictive value of the phenotypes against the gold standard of manually abstracted medical charts. Prevalence and incidence rates will be presented as unadjusted estimates and as race/ethnicity, sex and age-adjusted estimates using Poisson regression.Ethics and dissemination The DiCAYA Network is well positioned to advance diabetes surveillance methods. The network will disseminate EHR-based surveillance methodology that can be broadly adopted and will report diabetes prevalence and incidence for key demographic subgroups of youth and young adults in a large set of regions across the USA.

Abstract. Background:. Immunotherapies such as adoptive immune cell infusion and immune-modulating agents are widely used for cancer treatment, and the concomitant symptoms, including cytokine release syndrome (CRS) or immune-related adverse events (irAEs), are frequently reported. However, clinical manifestations induced by mismatched donor granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cell (GPBMC) infusion in patients receiving microtransplant (MST) have not yet been well depicted. Methods:. We analyzed 88 cycles of mismatched GPBMC infusion in patients with acute myeloid leukemia receiving MST and 54 cycles of chemotherapy without GPBMC infusion as a comparison. Clinical symptoms and their correlation with clinical features, laboratory findings, and clinical response were explored. Results:. Fever (58.0% [51/88]) and chills (43.2% [38/88]) were the significant early-onset symptoms after GPBMC infusion. Patients possessing less human leukocyte antigen-matching loci with the donor or those with unrelated donors experienced more chills (3 [2–5] loci vs. 5 [3–5] loci, P = 0.043 and 66.7% [12/18] vs. 37.1% [26/70], P = 0.024). On the other hand, those with decreased CD4+/CD8+ T-cell ratio developed more fever (0.8 [0.7–1.2] vs. 1.4 [1.1–2.2], P = 0.007). Multivariable analysis demonstrated that younger patients experienced more fever (odds ratio [OR] = 0.963, 95% confidence interval [CI]: 0.932–0.995, P = 0.022), while patients with younger donors experienced more chills (OR = 0.915, 95% CI: 0.859–0.975, P = 0.006). Elevated ultra-sensitive C-reactive protein levels in the absence of cytokine storm were observed following GPBMC infusion, which indicated mild and transient inflammatory response. Although no predictive value of infusion-related syndrome to leukemia burden change was found, the proportion of host pre-treatment activated T cells was positively correlated with leukemia control. Conclusions:. Mismatched GPBMC infusion in MST induced unique infusion-related symptoms and laboratory changes, which were associated with donor- or recipient-derived risk factors, with less safety and tolerance concerns than reported CRS or irAEs.

Abstract Background Direct estimates of rare disease prevalence from public health surveillance may only be available in a few catchment areas. Understanding variation among observed prevalence can inform estimates of prevalence in other locations. The Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) conducts population-based surveillance of major muscular dystrophies in selected areas of the United States. We identified sources of variation in prevalence estimates of Duchenne and Becker muscular dystrophy (DBMD) within MD STARnet from published literature and a survey of MD STARnet investigators, then developed a logic model of the relationships between the sources of variation and estimated prevalence. Results The 17 identified sources of variability fell into four categories: (1) inherent in surveillance systems, (2) particular to rare diseases, (3) particular to medical-records-based surveillance, and (4) resulting from extrapolation. For the sources of uncertainty measured by MD STARnet, we estimated each source’s contribution to the total variance in DBMD prevalence. Based on the logic model we fit a multivariable Poisson regression model to 96 age–site–race/ethnicity strata. Age accounted for 74% of the variation between strata, surveillance site for 6%, race/ethnicity for 3%, and 17% remained unexplained. Conclusion Variation in estimates derived from a non-random sample of states or counties may not be explained by demographic differences alone. Applying these estimates to other populations requires caution.

This study describes a novel species of Diploderma (Squamata, Agamidae) from the lower valley of the Dadu River of the Sichuan Province of Western China based on its distinct morphological features and molecular evidence. D. daduense sp. nov. can be distinguished from its congeners by its tympanum concealed; head mainly green-yellow, supplemented by black; skin folds under the nuchal and dorsal crest obviously present in adult males only, its vertebral crest discontinuous between nuchal and dorsal sections with a distinct gap; transverse gular fold present but not obvious in some individuals; gular spot absent in both sexes; dorsolateral stripes green-yellow anteriorly, cyan in the center and blurry off-white posteriorly in adult males, the upper edge of dorsolateral stripes strongly jagged in adult males; no radial stripes around the eyes; inner-lip coloration smoky-white, and the coloration of the tongue and oral cavity as a light-flesh color in life; bright green-yellow transverse stripes on dorsal body in males; black patches are evenly distributed along the vertebral line between the dorsolateral stripes from the neck to the base of the tail in males; beech-brown or gray-brown line along the vertebral line with heart-shaped or diamond-shaped black patches on the dorsal body in females; and supratemporals fewer than four on at least one side. The phylogenetic tree based on mitochondrial ND2 sequences indicates that D. daduense sp. nov. forms an independent clade with strong support 1/100 in ML bootstrap/Bayesian posterior probability and is the sister group to D. splendidum. At the inter-species level, the p-distance is at least 6.95%, further confirming that an independent species had been identified. Our work raises the number of species within the genus Diploderma to 47.

The Mongolian racerunner, Eremias argus, is a small lizard endemic to Northeast Asia that can serve as an excellent model for investigating how geography and past climate change have jointly influenced the evolution of biodiversity in this region. To elucidate the processes underlying its diversification and demography, we reconstructed the range-wide phylogeographic pattern and evolutionary trajectory, using phylogenetic, population genetic, landscape genetic, Bayesian phylogeographic reconstruction and ecological niche modeling approaches. Phylogenetic analyses of the mtDNA cyt b gene revealed eight lineages that were unbounded by geographic region. The genetic structure of E. argus was mainly determined by geographic distance. Divergence dating indicated that E. argus and E. brenchleyi diverged during the Mid-Pliocene Warm Period. E. argus was estimated to have coalesced at~0.4351 Ma (Marine Isotope Stage 19). Bayesian phylogeographic diffusion analysis revealed out-of-Inner Mongolia and rapid colonization events from the end of the Last Interglacial to the Last Glacial Maximum, which is consistent with the expanded suitable range of the Last Glacial Maximum. Pre-Last Glacial Maximum growth of population is presented for most lineages of E. argus. The Glacial Maximum contraction model and the previous multiple glacial refugia hypotheses are rejected. This may be due to an increase in the amount of climatically favorable habitats in Northeast Asia. Furthermore, E. argus barbouri most likely represents an invalid taxon. The present study is the first to report a range-wide phylogeography of reptiles over such a large region in Northeast Asia. Our results make a significant contribution towards understanding the biogeography of the entire Northeast Asia.

The potential distribution range and management strategies for P. viburni are poorly understood. Based on historical distribution data and environmental factors, the present study predicted the potentially suitable areas for P. viburni spread under different climate change scenarios using MaxEnt (maximum entropy). The results showed that precipitation of the coldest quarter (Bio19), precipitation seasonality (Bio15), and mean temperature of the wettest quarter (Bio8) were the most important environmental factors determining the distribution of P. viburni. Under the current climate conditions, its potential suitable areas are southern China, the whole of Japan, North America (especially the eastern part of the United States), the southwestern part of South America, the Mediterranean coast and most of Europe, the central part of Africa, i.e., the south of the Sahara Desert, and most of the southern coast of Australia. The total area of habitats suitable for this insect pest is predicted to be increased in the future. In order to prevent P. viburni transmission and spread, there is a need to strengthen the monitoring and quarantine measures against this pest at the Southern ports.

The papaya mealybug, Paracoccus marginatus, is an invasive pest species found all over the world. It is native to Mexico and Central America, but is now present in more than 50 countries and regions, seriously threatening the economic viability of the agricultural and forestry industry. In the current study, the global potential distribution of P. marginatus was predicted under current and future climatic conditions using MaxEnt. The results of the model assessment indicated that the area under the curve of the receiver operating characteristic ( ROC-AUC) was 0.949, while the TSS value was 0.820. The results also showed that the three variables with the greatest impact on the model were min temperature of coldest month (bio6), precipitation of wettest month (bio13), and precipitation of coldest quarter (bio19), with corresponding contributions of 46.8%, 31.1%, and 13.1%, respectively. The results indicated that the highly suitable areas were mainly located in tropical and subtropical regions, including South America, southern North America, Central America, Central Africa, Australia, the Indian subcontinent, and Southeast Asia. Under four climate scenarios in the 2050s and 2070s, the area of suitability will change very little. Moreover, the results showed that the area of suitable areas in 2070s increased under all four climate scenarios compared to the current climate. In contrast, the area of suitable habitat increases from the current to the 2050s under the SSP370 and SSP585 climate scenarios. The current study could provide a reference framework for the future control and management of papaya mealybug and other invasive species.

IntroductionPolyphyllin from Paris polyphylla var. yunnanensis exhibits anti-inflammatory, analgesic, antibacterial, and antiviral properties. However, the current production of polyphyllin can barely meet market demand. To improve the content of polyphyllin produced by P. polyphylla, two endophyte strains, Bacillus cereus LgD2 and Fusarium oxysporum TPB, were isolated from Paris fargesii Franch. and inoculated in the roots of P. polyphylla. Both symbiotic strains significantly promoted the accumulation of saponins in P. polyphylla.MethodsThe content of polyphyllin in rhizomes of P. polyphylla treated with TPB with LgD2 strain was determined using High Performance Liquid Chromatography and the expressed genes were analyzed by RNA-seq. Gene Ontology and Kyoto Encyclopedia of Genes annotations were performed on the differentially expressed genes, a clustering tree of UDP-glycosyltransferase (UGT) and cytochrome P450 (CYP450) gene families was constructed, and UGT and CYP450 involved in the biosynthesis of polyphyllin were predicted using weighted correlation network analysis (WGCNA).ResultsRNA-seq and qRT-PCR analyses showed that endophytic inoculation did not promote polyphyllin accumulation by enhancing the upstream terpene biosynthesis pathway, but probably by up-regulating the downstream CYP450 and UGT genes associated with polyphyllin biosynthesis. Genomes enrichment analyses of differentially expressed genes indicated that inoculation with LgD2 and TPB played a positive role in promoting the defense against pathogenic bacteria, enhancing the biosynthesis of carbohydrates, attenuating the process of nitrogen metabolism, and maintaining the equilibrium of the redox reaction homeostasis, potentially indirectly enhancing the polyphyllin yield of P. polyphylla. By combining differentially expressed genes screening, WGCNA, and phylogenetic tree analyses, 17 CYP450 and 2 UGT candidate genes involved in the biosynthesis of polyphyllin I, polyphyllin II, polyphyllin VII, polyphyllin D, and polyphyllin H were identified. These results suggest that endophytes probably effectively promote the accumulation of polyphyllin by regulating key downstream genes in biosynthetic pathways.DiscussionThis study provides a new approach for investigating the regulatory mechanisms of endophytes that promote the production and accumulation of polyphyllin in P. polyphylla, providing a basis for further elucidating the mechanisms of plant-endophyte interactions.

Background: Urethral strictures are common injurious conditions of the urinary system. Reducing and preventing urethral strictures has become a hot and challenging topic for urological surgeons and related researchers. In this study, we developed a catheter loaded with nanoparticle/pirfenidone (NP/PFD) complexes and evaluated its effectiveness at inhibiting urethral stricture in rabbits, providing more references for the clinical prevention and reduction of urethral stenosis.Methods: Twelve adult male New Zealand rabbits were selected and divided into the following four groups in a ratio of 1:1:1:1 using the random number table method: Group A, sham; Group B, urethral stricture (US); Group C, US + unmodified catheter; and Group D, US + NP/PFD catheter. On the 30th day after modelling, retrograde urethrography was performed to evaluate urethral stricture formation, and histopathological examination was performed on the tissues of the corresponding surgical site. Meanwhile, changes in the expression level of Transforming growth factor β1 (TGF-β1) in the tissues were detected by immunohistochemistry.Results: The NP/PFD complexes adhered uniformly to the catheter surface. They remained on the surface of the catheter after insertion into the urethra. In addition, the NP/PFD complexes spread into the urethral epithelium 2 weeks after surgery. Ultimately, urethral strictures were significantly reduced with the placement of the NP/PFD complex catheter.Conclusion: Our catheter loaded with NP/PFD complexes effectively delivered PFD to the urethral epithelium through continuous local delivery, thereby reducing fibrosis and stricture after urethral injury, which may be associated with the inhibition of TGF-β1 expression.

ObjectiveThis study aimed to provide a realistic observation of survival by major site for 48,866 cancer patients treated at a tertiary cancer hospital in a rural area of China.MethodsPatients with cancer registered between 2007 and 2017 in the Nantong rural area were followed up. The starting date for survival calculation was the date of the first diagnosis of cancer at the Nantong Tumor Hospital, and the closing date was December 31, 2020. Observed survival (OS) was analyzed according to ICD-10 site, sex, age, region, and hospitalization period using the life table method and compared using the Wilcoxon (Gehan) statistic.ResultsThe overall 5-year OS rate was 40.48% for all 48,866 patients, 30.19% for males, and 51.90% for females. The top five cancer sites, accounting for 60.51% of the total cases, were the esophagus, lung, stomach, liver, and cervix, with 5-year OS rates of 33.72%, 18.64%, 32.10%, 19.04%, and 71.51%, respectively. The highest 5-year OS was observed in the thyroid (87.52%) and the lowest was in the pancreas (6.37%). Survival was significantly higher in younger patients than in older patients, with 5-year OSs of 69.26% and 19.84% in those aged 20-29 and 90-99 years, respectively. Five-year OSs improved significantly from 39.35% in 2007-2011 to 41.26% in 2012-2017.ConclusionOverall survival improved over the years, although the improvement at some sites was not significant. The observed survival varies from region to region, reflecting differences in the patterns of major sites, disparities in proportions of hospitalization, and demographic characteristics.

The mitogenome of Dendroctonus rufipennis is a circular molecule of 16,547 bp which consists of 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes, and a control region (GenBank accession no. NC_063906). All of 13 PCGs initiate with the standard start codon of ATN. Most PCGs used the typical stop codon ‘TAA’ or ‘TAG’, only nad5 terminated with incomplete stop codon (TA). Phylogenetic analyses within the Scolytinae were performed based on nucleotide sequences of mitochondrial PCGs. The topology showed that D. rufipennis, D. valens, and Tomicus piniperda formed a clade, and also clustered together with Hylastes opacus, H. attenuatus, H. brunneus, and H. ater. This indicated that there is a close genetic relationship between these species.

Based on analysis of the reasons for low efficiency and low production after fracturing of some wells in the ultra-deep fractured tight reservoirs of the Kuqa piedmont zone, Tarim Basin and the matching relationship between the in-situ stress field and natural fractures, technological methods for creating complex fracture networks are proposed. Through theoretical study and large-scale physical simulation experiments, the mechanical conditions for forming complex fracture network in the Kuqa piedmont ultra-deep reservoirs are determined. The effectiveness of temporary plugging and diversion, and multi-stage fracturing to activate natural fractures and consequently realize multi-stage diversion is verified. The coupling effect of hydraulic fractures and natural fractures activating each other and resulting in “fracture swarms” is observed. These insights provide theoretical support for improving fracture-controlled stimulated reservoir volume (FSRV) in ultra-deep tight reservoirs. In addition, following the concept of volume fracturing technology and based on the results of fracture conductivity experiments of different processes, fracturing technologies such as multi-stage fracture-network acid fracturing, “multi-stage temporary plugging + secondary fracturing”, fracturing of multiple small layers by vertically softness-and-hardness-oriented subdivision, and weighted-fluid refracturing are proposed to increase the FSRV. New environment-friendly weighted-fluid with low cost and new fracturing fluid system with low viscosity and high proppant-carrying capacity are also developed. These techniques have achieved remarkable results in field application.

Tobacco black shank (TBS), caused by Phytophthora nicotianae, is one of the most harmful diseases of tobacco. There are many studies have examined the mechanism underlying the induction of disease resistance by arbuscular mycorrhizal fungi (AMF) and β-aminobutyric acid (BABA) alone, but the synergistic effects of AMF and BABA on disease resistance have not yet been studied. This study examined the synergistic effects of BABA application and AMF inoculation on the immune response to TBS in tobacco. The results showed that spraying BABA on leaves could increase the colonization rate of AMF, the disease index of tobacco infected by P.nicotianae treated with AMF and BABA was lower than that of P.nicotianae alone. The control effect of AMF and BABA on tobacco infected by P.nicotianae was higher than that of AMF or BABA and P.nicotianae alone. Joint application of AMF and BABA significantly increased the content of N, P, and K in the leaves and roots, in the joint AMF and BABA treatment than in the sole P. nicotianae treatment. The dry weight of plants treated with AMF and BABA was 22.3% higher than that treated with P.nicotianae alone. In comparison to P. nicotianae alone, the combination treatment with AMF and BABA had increased Pn, Gs, Tr, and root activity, while P. nicotianae alone had reduced Ci, H2O2 content, and MDA levels. SOD, POD, CAT, APX, and Ph activity and expression levels were increased under the combined treatment of AMF and BABA than in P.nicotianae alone. In comparison to the treatment of P.nicotianae alone, the combined use of AMF and BABA increased the accumulation of GSH, proline, total phenols, and flavonoids. Therefore, the joint application of AMF and BABA can enhance the TBS resistance of tobacco plants to a greater degree than the application of either AMF or BABA alone. In summary, the application of defense-related amino acids, combined with inoculation with AMF, significantly promoted immune responses in tobacco. Our findings provide new insights that will aid the development and use of green disease control agents.

Abstract Hepatitis B virus (HBV) infection remains a global health challenge. Despite the availability of effective preventive vaccines, millions of people are at risk of cirrhosis and hepatocellular carcinoma. Current drug therapies inhibit viral replication, slow the progression of liver fibrosis and reduce infectivity, but they rarely remove the covalently sealed circular DNA (cccDNA) of the virus that causes HBV persistence. Alternative treatment strategies, including those based on CRISPR/cas9 knockout virus gene, can effectively inhibit HBV replication, so it has a good prospect. During chronic infection, some virus gene knockouts based on CRISPR/cas9 may even lead to cccDNA inactivation. This paper reviews the progress of different HBV CRISPR/cas9, vectors for delivering to the liver, and the current situation of preclinical and clinical research.

The agamid lizard Phrynocephalus melanurus is restricted to Northwest China (Dzungar Basin) and the adjacent Eastern Kazakhstan (Zaisan and Alakol basins). To elucidate the phylogeography of P. melanurus, we obtained the mitochondrial DNA COI segments of 175 sampled lizards from 44 localities across the whole distribution. Phylogenetic analyses revealed two main Clades comprising five geographically structured lineages (I, IIa, IIb1, IIb2, and IIb3) that fit an isolation-by-distance (IBD) model. The divergence from the most recent common ancestor was dated to ~1.87 million years ago (Ma). Demographic analyses demonstrated lineage-specific response to past climate change: stable population for Clade I, Subclade IIb1; past population expansion for IIb3 since 0.18 Ma, respectively. Bayesian phylogeographic diffusion analyses detected initial spreading at the Saur Mount vicinity, approximately 1.8 Ma. Historical species distribution model (SDM) projected expansion of the suitable habitat in the last interglacial and shift and contraction in the last glacial maximum and Holocene epochs. The SDM predicted a drastic reduction in suitable area throughout the range as a response to future climate change. Our findings suggest that the evolution of P. melanurus followed a parapatric divergence with subsequent dispersal and adaptation to cold and dry environments during the Quaternary. Overall, this work improves our understanding of the lineage diversification and population dynamics of P. melanurus, providing further insights into the evolutionary processes that occurred in Northwest China and adjacent Eastern Kazakhstan.

This study describes a novel species of Gekko (Squamata: Gekkonidae) based on its distinct morphological features and molecular evidence, which was identified in the Dabie Mountains on the border of Anhui and Henan provinces of Central China. Gekko kaiyai sp. nov. could be distinguished from its congeners owing to its morphological characteristics, such as being a medium body sized gecko species (snout–vent length, 56.98–64.99 mm, n = 4, females; 50.03–61.56 mm, n = 11, males); nostrils scale in contact with rostral scale; tubercles on the dorsal and limb, while the upper forelimb is smooth with no tubercles; 22–33 interorbital scales between the anterior corners of the eyes; 157–209 ventral scales between mental and cloacal slit; 90–121 midbody scale rows; 30–43 ventral scale rows; 7–9 sub-digital lamellae on first fingers, 8–13 fourth fingers, 7–9 first toes, and 7–11 fourth toes; free of webbing in the fingers and toes; 9–12 pre-cloacal pores in males, which are absent in females; post-cloacal unilateral tubercles 1 (few 2); and a dorsum that is greyish white to dark brown, with 6–7 brown markings between the nape and sacrum. The phylogenetic tree based on the mitochondrial DNA sequences (16S, CYTB, and COI) indicated that Gekko kaiyai sp. nov. form an independent clade with strong support (100/1) and are a sister group to G. hokouensis. At the inter-species level, the genetic distances were all large, further confirming that an independent species had been identified. The discovery of this species implies that there are now 87 identified species in the genus Gekko, 22 of which can be found within China.

Quinoa is extensively cultivated for its nutritional value, and its exceptional capacity to endure elevated salt levels presents a promising resolution to the agricultural quandaries posed by salinity stress. However, limited research has been dedicated to elucidating the correlation between alterations in the salinity soil microbial community and nitrogen transformations. To scrutinize the underlying mechanisms behind quinoa’s salt tolerance, we assessed the changes in microbial community structure and the abundance of nitrogen transformation genes across three distinct salinity thresholds (1 g·kg−1, 3 g·kg−1, and 6 g·kg−1) at two distinct time points (35 and 70 days). The results showed the positive effect of quinoa on the soil microbial community structure, including changes in key populations and its regulatory role in soil nitrogen cycling under salt stress. Choroflexi, Acidobacteriota, and Myxococcota were inhibited by increased salinity, while the relative abundance of Bacteroidota increased. Proteobacteria and Actinobacteria showed relatively stable abundances across time and salinity levels. Quinoa possesses the ability to synthesize or modify the composition of keystone species or promote the establishment of highly complex microbial networks (modularity index > 0.4) to cope with fluctuations in external salt stress environments. Furthermore, quinoa exhibited nitrogen (N) cycling by downregulating denitrification genes (nirS, nosZ), upregulating nitrification genes (Archaeal amoA (AOA), Bacterial amoA (AOB)), and stabilizing nitrogen fixation genes (nifH) to absorb nitrate–nitrogen (NO3−_N). This study paves the way for future research on regulating quinoa, promoting soil microbial communities, and nitrogen transformation in saline environments.

Recent studies have shown that microtransplant (MST) could improve outcome of patients with elderly acute myeloid leukemia (EAML). To further standardize the MST therapy and improve outcomes in EAML patients, based on analysis of the literature on MST, especially MST with EAML from January 1st, 2011 to November 30th, 2022, the International Microtransplant Interest Group provides recommendations and considerations for MST in the treatment of EAML. Four major issues related to MST for treating EAML were addressed: therapeutic principle of MST (1), candidates for MST (2), induction chemotherapy regimens (3), and post-remission therapy based on MST (4). Others included donor screening, infusion of donor cells, laboratory examinations, and complications of treatment.

Purpose: To screen VSX1 gene sequence variations and describe the clinical features of families with keratoconus (KC) from northwest China.Methods: We screened VSX1 sequence variations and clinical data of 37 families including 37 probands with diagnosed KC from Ningxia Eye Hospital (China). VSX1 was screened by targeted next-generation sequencing (NGS) and verified by Sanger sequencing. In silico analysis including Mutation Taster, MutationAssessor, PROVEAN, MetaLR, FATHMM, M-CAP, FATHMM-XF_coding and DANN was performed to identify the pathogenicity of the sequence variations as well as the conserved amino acid variations of VSX1 was implemented by Clustal X. All subjects were assessed in Pentacam Scheimpflug tomography and corneal biomechanical Corvis ST examinations.Results: Five VSX1 gene variants, were identified in six (16.2%) unrelated families with KC. In silico analysis predicted deleterious effects of the three missense variants (p.G342E, p.G160V, and p.L17V) in the encoded protein. Another previously reported synonymous variation (p.R27R) in the first exon and one heterozygous change in the first intron (c.425-73C>T) were identified in three KC families. Clinical examination of the asymptomatic first-degree parents from these six families who shared the gene with the proband had suspected KC changes in topographic and biomechanical markers. These variants co-segregated with the disease phenotype in all affected individuals but not in unaffected family members or healthy controls, though with variable expressivity.Conclusion: The variant p.G342E of VSX1 is implicated in the pathogenesis of KC, which expands the range of the spectrum of VSX1 mutations with an autosomal dominant inheritance pattern and variable expression in the clinical phenotype. Genetic screening combined with clinical phenotype may help in the genetic counseling of patients with KC and identification of individuals with subclinical KC.

By systematically summarizing horizontal well fracturing technology abroad for shale oil and gas reservoirs since the “13th Five-Year Plan”, this article elaborates new horizontal well fracturing features in 3D development of stacked shale reservoirs, small well spacing and dense well pattern, horizontal well re-fracturing, fracturing parameters optimization and cost control. In light of requirements on horizontal well fracturing technology in China, we have summarized the technological progress in simulation of multi-fracture propagation, horizontal well frac-design, electric-drive fracturing equipment, soluble tools and low-cost downhole materials and factory-like operation. On this basis, combined with the demand analysis of horizontal well fracturing technology in the “14th Five-Year Plan” for unconventional shale oil and gas, we suggest strengthening the research and development in the following 7 aspects: (1) geology-engineering integration; (2) basic theory and design optimization of fracturing for shale oil and gas reservoirs; (3) development of high-power electric-drive fracturing equipment; (4) fracturing tool and supporting equipment for long horizontal section; (5) horizontal well flexible-sidetracking drilling technology for tapping remaining oil; (6) post-frac workover technology for long horizontal well; (7) intelligent fracturing technology.

The House-Tree-Person (HTP) sketch test is a psychological analysis technique designed to assess the mental health status of test subjects. Nowadays, there are mature methods for the recognition of depression using the HTP sketch test. However, existing works primarily rely on manual analysis of drawing features, which has the drawbacks of strong subjectivity and low automation. Only a small number of works automatically recognize depression using machine learning and deep learning methods, but their complex data preprocessing pipelines and multi-stage computational processes indicate a relatively low level of automation. To overcome the above issues, we present a novel deep learning-based one-stage approach for depression recognition in HTP sketches, which has a simple data preprocessing pipeline and calculation process with a high accuracy rate. In terms of data, we use a hand-drawn HTP sketch dataset, which contains drawings of normal people and patients with depression. In the model aspect, we design a novel network called Feature-Enhanced Bi-Level Attention Network (FBANet), which contains feature enhancement and bi-level attention modules. Due to the limited size of the collected data, transfer learning is employed, where the model is pre-trained on a large-scale sketch dataset and fine-tuned on the HTP sketch dataset. On the HTP sketch dataset, utilizing cross-validation, FBANet achieves a maximum accuracy of 99.07% on the validation dataset, with an average accuracy of 97.71%, outperforming traditional classification models and previous works. In summary, the proposed FBANet, after pre-training, demonstrates superior performance on the HTP sketch dataset and is expected to be a method for the auxiliary diagnosis of depression.

Acute lung injury (ALI) is a life-threatening disease that currently lacks a cure. Although stem cell-derived small extracellular vesicles (sEVs) have shown promising effects in the treatment of ALI, their underlying mechanisms and responsible components have yet to be identified. Proprotein convertase subtilisin/kexin type 6 (PCSK6) is a gene involved in inflammation and a potential target of miR-21-5p, a microRNA enriched in stem cell-derived sEVs. The current study investigated the role of PCSK6 in lipopolysaccharide (LPS)-induced ALI and its interaction with miR-21-5p. Notably, our results showed that PCSK6 expression was positively correlated with LPS stimulation. Knockdown of PCSK6 ameliorated LPS-induced inhibition of proliferation and upregulation of permeability in human BEAS-2B cells, whereas PCSK6 overexpression displayed the opposite effects. BEAS-2B cells were able to actively internalize the cocultured bone mesenchymal stem cell (MSC)-derived sEVs (BMSC-sEVs), which alleviated the cell damage caused by LPS. Overexpressing PCSK6, however, eliminated the therapeutic effects of BMSC-sEV coculture. Mechanistically, BMSC-sEVs inhibited PCSK6 expression via the delivery of miR-21-5p, which is directly bound to the PCSK6 gene. Our work provides evidence for the role of PCSK6 in LPS-induced ALI and identified miR-21-5p as a component of BMSC-derived sEVs that suppressed PCSK6 expression and ameliorated LPS-induced cell damage. These results reveal a novel molecular mechanism for ALI pathogenesis and highlight the therapeutic potential of using sEVs released by stem cells to deliver miR-21-5p for ALI treatment.

The soil dielectric constant model reflects the relationship between the volumetric water content and the dielectric constant. The ground penetrating radar (GPR) could quickly, precisely and non-destructively obtain the water state of the soil layers. A reasonable and reliable dielectric constant model is of great significance for predicting, monitoring and exploring water migration in soils. Taking Yunnan laterite as an example, this study comprehensively considered the key physical factors (dry density, water content, temperature) of the in situ laterite dielectric properties. The dielectric properties and the influencing factors of laterite has been discussed with the laboratory tests by reshaping laterite, and the dielectric constant model was finally proposed to evaluate the natural water state of the laterite. The results show that the relative dielectric constant of laterite increases gradually with the increasing volumetric water content, dry density and temperature respectively. The water content is the most important influencing factor, secondly followed by temperature and dry density. The dielectric constant model of laterite was built based on the influence of dry density and temperature on the relationship between the relative dielectric constant and volumetric water content. The proposed multivariate model has a good prediction effect on the water content of laterite, and the prediction effects compared with other existing models are as follows: Multivariate model, Zhao model, Malicki model, Zhou model, Topp model, Liao mode and Herkelrath model. This model could be applied to evaluate the plastic limit index and the liquid limit index using the relative dielectric constant, and then finally estimate the soft and hard state grades of laterite. This study could provide a reference for the construction of laterite dielectric constant models in different regions, and a convenient way for the estimation of the laterite water content state and engineering categories.

Abstract Hepatocellular carcinoma (HCC) is a heterogeneous tumor with an increased incidence worldwide accompanied by high mortality and dismal prognosis. Emerging evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes possess protective effects against various human diseases by transporting microRNAs (miRNAs or miRs). We aimed to explore the role of exosomal miR-15a derived from MSCs and its related mechanisms in HCC. Exosomes were isolated from transduced MSCs and co-incubated with Hep3B and Huh7 cells. miR-15a expression was examined by RT-qPCR in HCC cells, MSCs, and secreted exosomes. CCK-8, transwell, and flow cytometry were used to detect the effects of miR-15a or spalt-like transcription factor 4 (SALL4) on cell proliferative, migrating, invasive, and apoptotic properties. A dual-luciferase reporter gene assay was performed to validate the predicted targeting relationship of miR-15a with SALL4. Finally, in vivo experiments in nude mice were implemented to assess the impact of exosome-delivered miR-15a on HCC. The exosomes from MSCs restrained HCC cell proliferative, migrating, and invasive potentials, and accelerated their apoptosis. miR-15a was expressed at low levels in HCC cells and could bind to SALL4, thus curtailing the proliferative, migrating, and invasive abilities of HCC cells. Exosomes successfully delivered miR-15a to HCC cells. Exosomal miR-15a depressed tumorigenicity and metastasis of HCC tumors in vivo. Overall, exosomal miR-15a from MSCs can downregulate SALL4 expression and thereby retard HCC development.

BackgroundNeuropsychiatric symptoms (NPSs) lead to myriad poor health outcomes among individuals with Alzheimer’s disease (AD). Prior studies have observed associations between the various aspects of the home environment and NPSs, but macro-level environmental stressors (e.g., neighborhood income) may also disrupt the neuronal microenvironment and exacerbate NPSs. Yet, to our knowledge, no studies have investigated the relationship between the neighborhood environment and NPSs.MethodsUsing 2010 data among older adults with AD collected from a sample of the South Carolina Alzheimer’s Disease Registry, we estimated cross-sectional associations between neighborhood characteristics and NPSs in the overall population and by race/ethnicity. Neighborhood measures (within a 1/2-mile radius of residence) came from the American Community Survey and Rural Urban Commuting Area Code. We categorized median household income into tertiles: < $30,500, $30,500–40,000, and > $40,000, and rurality as: rural, small urban, and large urban. Residential instability was defined as the percent of residents who moved within the past year. NPSs were defined using the Neuropsychiatric Inventory Questionnaire that included the composite measure of all 12 domains. Adjusting for age, sex/gender, race/ethnicity, and caregiver educational attainment, we used negative binomial regression to estimate prevalence ratios (PR) and 95% confidence intervals (CI) for NPSs by neighborhood characteristics.ResultsAmong 212 eligible participants, mean age was 82 ± 8.7 years, 72% were women, and 55% non-Hispanic (NH)-Black. Individuals with AD living in < $30,500 vs. > $40,000 income neighborhoods had a 53% (PR = 1.53; 95% CI = 1.06–2.23) higher prevalence of NPSs while individuals living in rural vs. large urban neighborhoods had a 36% lower prevalence of NPSs (PR = 0.64; 95% CI = 0.45–0.90), after adjustment. We did not observe an association between residential instability and NPSs (PR = 0.92; 95% CI = 0.86–1.00); however, our estimates suggested differences by race/ethnicity where NH-White older adults living in residential instable areas had lower NPSs (PR = 0.89; 95% CI = 0.82–0.96) compared to NH-Black older adults (PR = 0.96; 95% CI = 0.86–1.07).DiscussionAcross racial/ethnic groups, individuals with AD had more symptomology when living in lower income areas. Pending replication, intervention efforts should consider resource allocation to high-need neighborhoods (e.g., lower income), and studies should investigate underlying mechanisms for this relationship.