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Abstract Background Postoperative insulin resistance (PIR) represents an important characteristic of metabolic response following surgical injury. Clinical outcomes are negatively correlated to postoperative insulin resistance and hyperglycemia, indicating a novel treatment for reducing postoperative insulin resistance is urgently needed. The current work aimed to assess the protective effects of branched-chain amino acids (BCAA) on glucose metabolism disorders induced surgically in a rat model, and to explore the underpinning mechanism. Methods and results Rats were randomly assigned to 2 groups, including the control and BCAA groups. Rats were given a compulsory oral 3 mL load by gavage two hours before surgery. The results showed that BCAA remarkably reduced glycemia by suppressing liver gluconeogenesis via reduction of cAMP-response element-binding protein-regulated transcription coactivator 2 (CRTC2) and glucose-6-phosphatase (G6PC) gene and protein expression levels (all Ps

Abstract PA-enhanced content causes astringency in persimmon fruit. PCNA persimmons can lose their astringency naturally and they become edible when still on the tree, which allows for conserves of physical and financial resources. C-PCNA persimmon originates in China. Its deastringency trait primarily depends on decreased PA biosynthesis and PA insolubilization at the late stage of fruit development. Although some genes and transcription factors that may be involved in the deastringency of C-PCNA persimmon have been reported, the expression patterns of these genes during the key deastringency stage are reported less. To investigate the variation in PA contents and the expression patterns of deastringency-related genes during typical C-PCNA persimmon ‘Xiaoguo-tianshi’ fruit development and ripening, PA content and transcriptional profiling were carried out at five late stages from 70 to 160 DAF. The combinational analysis phenotype, PA content, and DEG enrichment revealed that 120–140 DAF and 140–160 DAF were the critical phases for PA biosynthesis reduction and PA insolubilization, respectively. The expression of PA biosynthesis-associated genes indicated that the downregulation of the ANR gene at 140–160 DAF may be associated with PA biosynthesis and is decreased by inhibiting its precursor cis-flavan-3-ols. We also found that a decrease in acetaldehyde metabolism-associated ALDH genes and an increase in ADH and PDC genes might result in C-PCNA persimmon PA insolubilization. In addition, a few MYB-bHLH-WD40 (MBW) homologous transcription factors in persimmon might play important roles in persimmon PA accumulation. Furthermore, combined coexpression network analysis and phylogenetic analysis of MBW suggested that three putative transcription factors WD40 (evm.TU.contig1.155), MYB (evm.TU.contig8910.486) and bHLH (evm.TU.contig1398.203), might connect and co-regulate both PA biosynthesis and its insolubilization in C-PCNA persimmon. The present study elucidated transcriptional insights into PA biosynthesis and insolubilization during the late development stages based on the C-PCNA D. kaki genome (unpublished). Thus, we focused on PA content variation and the expression patterns of genes involved in PA biosynthesis and insolubilization. Our work has provided additional evidence on previous knowledge and a basis for further exploration of the natural deastringency of C-PCNA persimmon.

The motivation of the present study is to explore ratcheting-fatigue behavior and the corresponding micro-deformation mechanism of ultrafine-grained aluminum alloys 6061 (UFG AA6061) under two stress-controlled low-cycle fatigue (LCF) loading modes, i.e., mean tension stress (MTS) and mean compressive stress (MCS). The uniaxial ratcheting tests demonstrate that the fatigue-ratcheting damage of UFG AA6061 is prone to occur under MCS-LCF loading, rather than MTS-LCF loading. Detailed microstructure characterizations by Electron backscatter diffraction (EBSD) techniques under these two loading modes show that the grain aspect ratios decrease greatly and the fractions of high angle boundaries increase remarkably in the case of MCS-LCF loading. These observations are mainly ascribed to the room temperature continuous dynamic recrystallization (CDRX), in which low angle boundaries evolve into high angle grain boundaries and the formation of equiaxed grains is accelerated. In contrast, there were no obvious change in the grain aspect ratios or the fractions of high angle boundaries at MTS-LCF loading condition, while the Schmid factor of non-octahedral slip system {100} increases and the texture evolve gradually. The deformation mechanism is grain boundary sliding (GBS) and grain rotation would accommodate the process of GBS. An analysis of the microstructure-properties relationship showed the superposition effect of residual shear deformation and uniaxial LCF ratcheting deformation is responsible for the CDRX at room temperature. And the occurrence of GBS is mainly caused by the activation of non-octahedral slip system.

Abstract Concerning the distance protection steady‐state over‐reach or under‐reach caused by the transition resistance, a novel distance protection scheme based on transient information is proposed. First, multiple fault features are extracted using the Generalized Stockwell Transform (GST), and a criterion for identifying low‐resistance and high‐resistance ground faults is constructed. Then, a GST coefficient matrix is established for the single‐ended transient voltage of the line, the attenuation coefficient and delay coefficient are derived by the least‐squares method and the beat phenomenon, and the transition resistance is calculated. On this basis, adjust the operation boundary in the +R axis direction of the operation zone according to the transition resistance value. Finally, test results on real‐time digital simulation system (RTDS) demonstrate that the protection scheme operates reliably in different fault cases and is highly immune to fault resistance. Compared with the traditional distance protection scheme, this scheme performs better when the transition resistance is large.

Abstract Background Metastatic breast carcinoma is commonly considered during differential diagnosis when metastatic disease is detected in females. In addition to the tumor morphology and documented clinical history, sensitive and specific immunohistochemical (IHC) markers such as GCDFP-15, mammaglobin, and GATA3 are helpful for determining breast origin. However, these markers are reported to show lower sensitivity in certain subtypes, such as triple-negative breast cancer (TNBC). Materials and methods Using bioinformatics analyses, we identified a potential diagnostic panel to determine breast origin: matrix Gla protein (MGP), transcriptional repressor GATA binding 1 (TRPS1), and GATA-binding protein 3 (GATA3). We compared MGP, TRPS1, and GATA3 expression in different subtypes of breast carcinoma of (n = 1201) using IHC. As a newly identified marker, MGP expression was also evaluated in solid tumors (n = 2384) and normal tissues (n = 1351) from different organs. Results MGP and TRPS1 had comparable positive expression in HER2-positive (91.2% vs. 92.0%, p = 0.79) and TNBC subtypes (87.3% vs. 91.2%, p = 0.18). GATA3 expression was lower than MGP (p

Objective To investigate the serological and molecular characteristics of HBsAg+ /HBV DNA non-reactive (NR) infections. Methods Samples tested as HBsAg+ and HBV DNA NR were confirmed by individual NAT repeat testing, viral particle concentration by PEG precipitation combined with in-house nested PCR and real-time quantitative PCR, anti-HBc testing, and HBsAg quantification. HBV sequences were compared with those from donors with chronic and occult infection as controls. Results A total of 792 195 samples were screened between January 2011 and December 2020, of which 53 (1: 14 947) were confirmed HBsAg+ /HBV DNA NR. HBV DNA was detected further in five (9.4%) samples; three S sequences and four Pre Core/Core sequences were obtained. Unique amino acid substitutions (P130T, P135Q/S, R151Q, G153S and S155F) were found in the Core protein that may affect virus packaging and replication. Conclusion Extremely low HBV DNA level was detected in plasmas of HBsAg+ /HBV DNA NR donors. Barely detectable HBV DNA might be associated with unusual mutations in the Pre Core/Core protein affecting viral replication. More sensitive HBV DNA and/or HBsAg assays may be considered to further reduce the potential HBV transfusion-transmission residual risk.

Given the difficulties of degrading benzotriazole (BTA), this study used a one-pot hydrothermal method to prepare α-Fe2O3/Cu2O (FC) composites for photoelectrocatalytic (PEC) degradation of BTA. The characterization of FC structure showed that Cu2O in cubic crystals was loaded with circular sheets of Fe2O3. Owing to this structure, FC showed efficient PEC degradation of BTA when exposed to ultraviolet light. The experimental results demonstrated that FC efficiently degraded BTA. When the PEC degradation continued for 60 min, 100% degradation of BTA was achieved because FC enhanced the photoelectron-hole separation and the separation and transfer of articulated carriers. High performance liquid chromatography–mass spectrometry showed that intermediates formed during the PEC degradation of BTA. Finally, various pathways for degradation of BTA were postulated. This FC-based PEC system provides a harmless and effective method for degradation of BTA.

We aimed to determine the effects of dietary supplementation with galacto-oligosaccharides (GOS) on the growth performance, serum parameters, and the rumen microbial colonization and fermentation of pre-weaning dairy calves. The study comprised 2 phases of 28 and 42 d, respectively. During phase 1, 24 newborn female Holstein dairy calves were randomly allocated to consume a diet supplemented with 10 g/d GOS (GOS, n = 12) or not (CON, n = 12). Thereafter, during phase 2, the GOS group was further divided into 2 groups: one that continued to consume GOS (GOSC, n = 6) and one that no longer consumed GOS (GOSS, n = 6), alongside the CON group. Galacto-oligosaccharides increased the average daily gain (ADG), body weight, feed efficiency, and serum high-density lipoprotein-cholesterol concentration of dairy calves during phase 1 (P

Abstract To investigate the effect of long noncoding RNA (LINC01419)/miR‐485‐5p/LSM4 on the malignant behavior of hepatocellular carcinoma (HCC) cells. The expressions of LINC01419, miR‐485‐5p, and LSM4 were determined in HCC at the cellular and clinical levels, and cell biological behavior was evaluated. The relationships between LINC01419, miR‐485‐5p, and LSM4 were predicted and verified. Additionally, the subcellular localization of LINC01419 in HCC cells was analyzed. Finally, an animal experiment was conducted to confirm the effect of LINC01419 silencing on tumor growth. in HCC tissues and cells, LINC01419 and LSM4 were increasingly expressed, but miR‐485‐5p was decreasingly expressed. LINC01419 negatively regulated miR‐485‐5p‐ and miR‐485‐5p‐targeted LSM4. LINC01419 was localized in the cytoplasm of HCC cells. Downregulation of miR‐485‐5p or upregulation of LSM4 reversed the inhibition of HCC cell malignant behavior by LINC01419 interference. LINC01419 sponges miR‐485‐5p to upregulate LSM4 expression, thereby facilitating the biological behavior of HCC cells.

Abstract This paper comprehensively investigates the current distribution behaviours of paralleled SiC MOSFET devices under the parasitic coupling between gate and power loops. Three types of connection that are commonly adopted in actual applications, comprising common source connection (CSC), Kelvin source connection (KSC) and hybrid source connection (HSC), are thoroughly discussed. The influence mechanism of mismatch in values for three parasitic inductances on current sharing during different switching periods is studied in theory. Simulations and experiments are also carried out and results are used to validate the theoretical analysis. Parasitic capacitance, common source and quasi common source parasitic inductance couplings are the three main coupling modes between gate loop and power loop in a circuit with paralleled SiC MOSFETs. The current imbalance is mainly due to the variation of gate‐source voltage generated by the mismatch in the parasitic inductances through the three coupling paths. This paper aims to provide an insight into current sharing mechanism of paralleled devices with circuit parasitic mismatches. Influence of every parasitic inductance under each of the three coupling modes is investigated and recommendation made on choice of coupling mode and viable switching speed and current balance tradeoff that can be adopted in a practical system design.

Development of methods for simultaneous single cell analysis of transcription and translation is still underway. Here, Hu et al. develop single-cell transcriptome and translatome dual-omics on human oocytes, which enables them to identify OOSP2 as an induction factor during human oocyte maturation.

AIM: To compare the postoperative efficacy of corneal wavefront-guided femtosecond laser-assisted excimer in situ keratomileusis(FS-LASIK)in the treatment of myopia patients with different degrees of astigmatism and the changes of corneal higher order aberration.METHODS: A total of 133 patients(265 eyes)with myopia and astigmatism were enrolled in this retrospective study. All of them underwent corneal wavefront-guided FS-LASIK surgery for the first time in Aier Eye Hospital(Kunming)from April to October 2020. The patients were divided into three groups according to the different astigmatism: Low astigmatism group: astigmatism ≤1.0D, 62 cases(124 eyes), medium astigmatism group: a total of 54 cases(107 eyes)with astigmatism was 1.25-2.0D, high astigmatism group: a total of 17 cases(34 eyes)with astigmatism ≥2.25D. Visual acuity and refraction were recorded before surgery and 3mo after the surgery and the cornea of the patients was measured by Pentacam three-dimensional corneal topography. Record total higher order aberrations(root mean square), spherical aberration, horizontal coma, vertical coma, horizontal clover and oblique clover in the 6mm diameter range of the cornea. The postoperative effects of the three groups of patients were observed and the changes of corneal high order aberration before and after surgery were compared. RESULTS: The validity index of visual acuity in the three groups of patients was all greater than 1.1 and the residual diopter was all within ±0.30D. The residual diopter in the low astigmatism group was the least than that of the other two groups(P

The microRNA miR-21 is induced in the islets of patients with glucose intolerance and diabetic mice. Here the authors report that deletion of miR-21 in pancreatic β-cells impairs glucose-stimulated insulin secretion via reduced glucose uptake, while a miR-21 agomir reduces blood glucose leves in diabetic male mice.

In 2020 and 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, caused a global pandemic. Vaccines are expected to reduce the pressure of prevention and control, and have become the most effective strategy to solve the pandemic crisis. SARS-CoV-2 infects the host by binding to the cellular receptor angiotensin converting enzyme 2 (ACE2) via the receptor-binding domain (RBD) of the surface spike (S) glycoprotein. In this study, a candidate vaccine based on a RBD recombinant subunit was prepared by means of a novel glycoengineered yeast Pichia pastoris expression system with characteristics of glycosylation modification similar to those of mammalian cells. The candidate vaccine effectively stimulated mice to produce high-titer anti-RBD specific antibody. Furthermore, the specific antibody titer and virus-neutralizing antibody (NAb) titer induced by the vaccine were increased significantly by the combination of the double adjuvants Al(OH)3 and CpG. Our results showed that the virus-NAb lasted for more than six months in mice. To summarize, we have obtained a SARS-CoV-2 vaccine based on the RBD of the S glycoprotein expressed in glycoengineered Pichia pastoris, which stimulates neutralizing and protective antibody responses. A technical route for fucose-free complex-type N-glycosylation modified recombinant subunit vaccine preparation has been established.

Abstract Background Corneal transplantation is the only way to treat serious corneal diseases caused by corneal endothelial dysfunction. However, the shortage of donor corneal tissues and human corneal endothelial cells (HCECs) remains a worldwide challenge. We cultivated HCECs by the use of a conditioned medium from orbital adipose-derived stem cells (OASC-CM) in vitro. Then the HCECs were used to treat animal corneal endothelial dysfunction models via cell transplantation. The purpose of this study was to conduct a long-term observation and evaluation after cell transplantation. Methods Orbital adipose-derived stem cells (OASCs) were isolated to prepare the conditioned medium (CM). HCECs were cultivated and expanded by the usage of the CM (CM-HCECs). Then, related corneal endothelial cell (CEC) markers were analyzed by immunofluorescence. The cell proliferation ability was also tested. CM-HCECs were then transplanted into monkey corneal endothelial dysfunction models by injection. We carried out a 24-month postoperative preclinical observation and verified the long-term effect by histological examination and transcriptome sequencing. Results CM-HCECs strongly expressed CEC-related markers and maintained polygonal cell morphology even after 10 passages. At 24 months after cell transplantation, there was a CEC density of more than 2400 cells per square millimeter (range, 2408–2685) in the experimental group. A corneal thickness (CT) of less than 550 μm (range, 490–510) was attained. Gene sequencing showed that the gene expression pattern of CM-HCECs was similar to that of transplanted cells and HCECs. Conclusions Transplantation of CM-HCECs into monkey corneal endothelial dysfunction models resulted in a transparent cornea after 24 months. This research provided a promising prospect of cell-based therapy for corneal endothelial diseases.

Abstract In order to further improve the prediction accuracy of typhoon simulation method for extreme wind speed in typhoon prone areas, an improved typhoon simulation method is proposed by introducing the Latin hypercube sampling method into the traditional typhoon simulation method. In this paper, the improved typhoon simulation method is first given a detailed introduction. Then, this method is applied to the prediction of extreme wind speeds under various return periods in Hong Kong. To validate this method, two aspects of analysis is carried out, including correlation analysis among typhoon key parameters and prediction of extreme wind speeds under various return periods. The results show that the correlation coefficients among typhoon key parameters can be maintained satisfactorily with this improved typhoon simulation method. The results show that the improved typhoon simulation method can generate the correlations among all typhoon key parameters satisfactorily. Compared with the traditional typhoon simulation method, the improved typhoon simulation method has higher accuracy in predicting the typhoon extreme wind speed in Hong Kong, increasing by about 8% and 11% respectively at 200 m height and gradient height.

Mesenchymal stem cells (MSC) are particularly effective in promoting cartilage regeneration due to their immunomodulatory, anti-inflammatory and regenerative repair functions of tissues and organs. Meanwhile, the intra-articular delivery and synergy with other therapeutic drugs have been the key issues driving their further application. We report a mussel-inspired multifunctional hydrogel system, which could achieve co-delivery and synergism effect of MSC-derived exosomes (Exos) with icariin (ICA). The ICA and Exos co-delivered articular cavity injection system are expected to retain in the joint cavity and promote cartilage regeneration, due to the thermosensitive, self-healing and adhesion properties of the mussel-inspired multifunctional hydrogel. The experimental results proved that Exos enhanced the cellular uptake of ICA by more than 2-fold evenly, and the synergism of Exos and ICA efficiently improve the cell proliferation and migration. After synergic treatment, the content of matrix metalloproteinase 13 in the supernatant and intracellular decreased by 47% and 59%, respectively. In vivo study, ICA-loaded Exos exhibited prolonged retention behavior by multifunctional hydrogel delivery, thus displayed an increased cartilage protection. In the model of osteoarthritis, co-delivery hydrogel system relieved the cartilage recession, ensuring appropriate cartilage thickness.

Background: Previous studies have shown that the 5-year survival rates of patients with nasopharyngeal carcinoma (NPC) were still not ideal despite great improvement in NPC treatments. To achieve individualized treatment of NPC, we have been looking for novel models to predict the prognosis of patients with NPC. The objective of this study was to use a novel deep learning network structural model to predict the prognosis of patients with NPC and to compare it with the traditional PET-CT model combining metabolic parameters and clinical factors. Methods: A total of 173 patients were admitted to 2 institutions between July 2014 and April 2020 for the retrospective study; each received a PET-CT scan before treatment. The least absolute shrinkage and selection operator (LASSO) was employed to select some features, including SUVpeak-P, T3, age, stage II, MTV-P, N1, stage III and pathological type, which were associated with overall survival (OS) of patients. We constructed 2 survival prediction models: an improved optimized adaptive multimodal task (a 3D Coordinate Attention Convolutional Autoencoder and an uncertainty-based jointly Optimizing Cox Model, CACA-UOCM for short) and a clinical model. The predictive power of these models was assessed using the Harrell Consistency Index (C index). Overall survival of patients with NPC was compared by Kaplan–Meier and Log-rank tests. Results: The results showed that CACA-UOCM model could estimate OS (C index, 0.779 for training, 0.774 for validation, and 0.819 for testing) and divide patients into low and high mortality risk groups, which were significantly associated with OS ( P

Hepatocellular carcinoma (HCC) is a malignant tumor with high recurrence and metastasis rates and poor prognosis. Basement membrane is a ubiquitous extracellular matrix and is a key physical factor in cancer metastasis. Therefore, basement membrane-related genes may be new targets for the diagnosis and treatment of HCC. We systematically analyzed the expression pattern and prognostic value of basement membrane-related genes in HCC using the TCGA-HCC dataset, and constructed a new BMRGI based on WGCNA and machine learning. We used the HCC single-cell RNA-sequencing data in GSE146115 to describe the single-cell map of HCC, analyzed the interaction between different cell types, and explored the expression of model genes in different cell types. BMRGI can accurately predict the prognosis of HCC patients and was validated in the ICGC cohort. In addition, we also explored the underlying molecular mechanisms and tumor immune infiltration in different BMRGI subgroups, and confirmed the differences in response to immunotherapy in different BMRGI subgroups based on the TIDE algorithm. Then, we assessed the sensitivity of HCC patients to common drugs. In conclusion, our study provides a theoretical basis for the selection of immunotherapy and sensitive drugs in HCC patients. Finally, we also considered CTSA as the most critical basement membrane-related gene affecting HCC progression. In vitro experiments showed that the proliferation, migration and invasion abilities of HCC cells were significantly impaired when CTSA was knocked down.

IntroductionPTGES3, also known as p23, is a molecule chaperone of Hsp90 that is involved in the pathogenesis of malignant tumors. Increasing studies have shown that PTGES3 plays a nonnegligible role in tumor development. However, analysis of PTGES3 in pan-cancer has not been performed yet.MethodsWe explored the role of PTGES3 in 33 types of tumors and depicted the potentialimmune-related pathways among them. Using multiple databases includingTCGA, LinkedOmics, GDSC, and TIMER, we made a comprehensive analysis to explore whether there was an interaction between PTGES3 and prognosis, DNA methylation, copy number variation (CNV), tumor mutational burden (TMB), microsatellite instability (MSI), and tumor immune microenvironment (TME).ResultsOur study revealed that PTGES3 expression level was upregulated in most cancers. PTGES3 was also associated with a positive or negative prognosis in a variety of cancers, which was mainly associated with DNA methylation, CNV, MSI, TMB, andmismatch repair-related genes. High PTGES3 expression was related to the infiltration of Th2 subsets of CD4+ T cells and immune checkpoint-related genes in most cancers, especially in hepatocellular carcinoma (HCC). Enrichment analysis demonstrated that PTGES3 was involved in cellular processes including DNA replication and spliceosome. The relationship between PTGES3 expression and HCC progression was verified at the protein level through immune histochemical analysis.ConclusionsOur research demonstrated theprognostic predictive value of PTGES3 in a wide range of cancers, which was alsoassociated with the process of tumor immune infiltration. As a result, it suggestedthat PTGES3 was a valuable prognostic biomarker in HCC treatment.

Abstract Tumor protein 53 (TP53) mutation in bladder carcinoma (BC), upregulates the transcription of carbamoyl phosphate synthetase 1 (CPS1), to reduce intracellular ammonia toxicity. To leverage ammonia combating BC, here, an intravesically perfusable nanoporter‐encased hydrogel system is reported. A biomimetic fusogenic liposomalized nanoporter (FLNP) that is decorated with urea transporter‐B (UT‐B) is first synthesized with protonated chitosan oligosaccharide for bladder tumor‐targeted co‐delivery of urease and small interfering RNA targeting CPS1 (siCPS1). Mussel‐inspired hydrogel featured with dual functions of bio‐adhesion and injectability is then fabricated as the reservoir for intravesical immobilization of FLNP. It is found that FLNP‐mediated UT‐B immobilization dramatically induces urea transportation into tumor cells, and co‐delivery of urease and siCPS1 significantly boosts ammonia accumulation in tumor inducing cell apoptosis. Treatment with hybrid system exhibits superior anti‐tumor effect in orthotopic bladder tumor mouse model and patient‐derived xenograft model, respectively. Combined with high‐protein diet, the production of urinary urea increases, leading to an augmented intracellular deposition of ammonia in BC cells, and ultimately an enhanced tumor inhibition. Together, the work establishes that cascade modulation of ammonia in tumor cells could induce tumor apoptosis and may be a practical strategy for eradication of TP53‐mutated bladder cancer.

IntroductionSalvia miltiorrhiza Bunge is an important medicinal herb, which is widely cultivated in most parts of China. It has attracted considerable attention because of its pharmacological properties and potential health benefits.MethodsWe used a field experiment to determine the effects of different genotypes and climatic factors on the performance (plant biomass, morphological parameters), active ingredients, rhizosphere soil physicochemical properties and microbial composition of S. miltiorrhiza at five cultivation locations.ResultsThe results showed that these parameters were significantly different in the six different genotypes of S. miltiorrhiza from five producing areas. Genotype and soil physicochemical properties were the main factors affecting the growth traits of S. miltiorrhiza, while genotype, climate and soil physicochemical properties were the main factors affecting the content of active components of S. miltiorrhiza. Microbial phospholipid fatty acid analysis showed that the biomass of Gram-positive and Gram-negative bacteria was affected by the genotypes of S. miltiorrhiza plants, while the biomass of arbuscular mycorrhizal fungi, fungi, Gram-positive and Gram-negative bacteria was affected by climate factors.DiscussionBased on the main results, DS993 was the most suitable genotype for S. miltiorrhiza in the five producing areas from the perspective of comprehensive growth traits and medicinal components, while DS993 and DS2000 were suitable for planting in Shandong province from the perspective of origin. DS996 is not suitable for all of the above production areas. These results are helpful to understand the ecological adaptability of different genotypes of S. miltiorrhiza resources, and to select appropriate S. miltiorrhiza genotypes for specific planting areas, so as to maximize yield and quality.

Photoacoustic tomography emerged as a promising tool for noninvasive biomedical imaging and diseases diagnosis. However, most of the current piezoelectric ultrasound transducers suffer optical opacity and tissue-mismatched acoustic impedance, hindering the miniaturization and integration of the system for multiscale and multimodal imaging. Here, a transparent polydimethylsiloxane (PDMS) encapsulated optical microfiber ultrasound sensor was demonstrated for photoacoustic imaging with scalable spatial resolution and penetration depth. The sensor comprised a microfiber loop sandwiched by a pair of in-line Bragg gratings, which formed an ultrasound-sensitive Fabry-Perot cavity allowing free delivery of ultrasound/light beams and unique needle-shaped ultrasound focusing along the penetration depth. The sensor with a detection limit of ∼ 700 Pa and a bandwidth of ∼ 10 MHz was applied for multiscale photoacoustic imaging of mouse ear and brain vasculatures. With advantages of flexibility, optical transparence and focusing capability, the sensor offers new opportunities for developing photoacoustic/ultrasound imaging devices for biomedical and clinic applications.

Intestinal inflammation is a protective response that is implicated in bacterial enteritis triggered by gastrointestinal infection. The immune mechanisms elicited in teleost against the infection of Aeromonas veronii are largely unknown. In this study, we performed a de novo northern snakehead (Channa argus) transcriptome assembly using Illumina sequencing platform. On this basis we performed a comparative transcriptomic analysis of northern snakehead intestine from A. veronii-challenge and phosphate buffer solution (PBS)-challenge fish, and 2076 genes were up-regulated and 1598 genes were down-regulated in the intestines infected with A. veronii. The Gene Ontology (GO) enrichment analysis indicated that the differentially expressed genes (DEGs) were enriched to 27, 21 and 20 GO terms in biological process, cellular component, and molecular function, respectively. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 420 DEGs were involved in 194 pathways. Moreover, 33 DEGs were selected for quantitative real-time PCR analysis to validate the RNA-seq data. The results reflected the consistency of the expression levels between qRT-PCR and RNA-seq data. In addition, a time-course analysis of the mRNA expression of 33 immune-related genes further indicated that the intestinal inflammation to A. veronii infection simultaneously regulated gene expression alterations. The present study provides transcriptome data of the teleost intestine, allowing us to understand the mechanisms of intestinal inflammation triggered by bacterial pathogens. Data availability statement: All data supporting the findings of this study are available within the article and Supplementary files. The RNA-seq raw sequence data are available in NCBI short read archive (SRA) database under accession number PRJNA615958.

BackgroundVirtual and augmented reality (VAR) represents a combination of current state-of-the-art computer and imaging technologies and has the potential to be a revolutionary technology in many surgical fields. An increasing number of investigators have developed and applied VAR in hip-related surgery with the aim of using this technology to reduce hip surgery–related complications, improve surgical success rates, and reduce surgical risks. These technologies are beginning to be widely used in hip-related preoperative operation simulation and training, intraoperative navigation tools in the operating room, and postoperative rehabilitation. ObjectiveWith the aim of reviewing the current status of virtual reality (VR) and augmented reality (AR) in hip-related surgery and summarizing its benefits, we discussed and briefly described the applicability, advantages, limitations, and future perspectives of VR and AR techniques in hip-related surgery, such as preoperative operation simulation and training; explored the possible future applications of AR in the operating room; and discussed the bright prospects of VR and AR technologies in postoperative rehabilitation after hip surgery. MethodsWe searched the PubMed and Web of Science databases using the following key search terms: (“virtual reality” OR “augmented reality”) AND (“pelvis” OR “hip”). The literature on basic and clinical research related to the aforementioned key search terms, that is, studies evaluating the key factors, challenges, or problems of using of VAR technology in hip-related surgery, was collected. ResultsA total of 40 studies and reports were included and classified into the following categories: total hip arthroplasty, hip resurfacing, femoral neck fracture, pelvic fracture, acetabular fracture, tumor, arthroscopy, and postoperative rehabilitation. Quality assessment could be performed in 30 studies. Among the clinical studies, there were 16 case series with an average score of 89 out of 100 points (89%) and 1 case report that scored 81 (SD 10.11) out of 100 points (81%) according to the Joanna Briggs Institute Critical Appraisal Checklist. Two cadaveric studies scored 85 of 100 points (85%) and 92 of 100 points (92%) according to the Quality Appraisal for Cadaveric Studies scale. ConclusionsVR and AR technologies hold great promise for hip-related surgeries, especially for preoperative operation simulation and training, feasibility applications in the operating room, and postoperative rehabilitation, and have the potential to assist orthopedic surgeons in operating more accurately and safely. More comparative studies are necessary, including studies focusing on clinical outcomes and cost-effectiveness.

Natural astaxanthin is a high-value ketone carotenoid mainly derived from Haematococcus pluvialis, which is an excellent antioxidant for human consumption. To study the role of lipids in accumulation of astaxanthin, the H. pluvialis-derived astaxanthin synthesis pathway genes (β-carotene ketolase gene, BKT and β-carotene hydroxylase gene, BCH) and fatty acid elongation gene (mitochondrial trans-2-enoyl-coa reductase gene, MECR) were heterologously co-expressed in C. reinhardtii. Zeaxanthin, the precursor of astaxanthin synthesis, was significantly increased after BKT and BCH were expressed. In contrast, the α-carotene that competes with astaxanthin synthesis for lycopene decreased significantly. This redistribution of carbon flow was conducive to the synthesis of astaxanthin. In addition, the transformant only expressed astaxanthin metabolism related genes (BKT, BCH) would lead to an increase in total lipid, a decrease in monounsaturated fatty acids and an increase in polyunsaturated fatty acids. On this basis, the expression of MECR gene further increased the total lipid, and the relative content of different fatty acids also changed. The astaxanthin content of algal strains transformed with BKT and BCH genes was nearly 50% higher than that of the wild type. On this basis, the astaxanthin content of transformants expressing MECR gene related to long-chain fatty acid synthesis was increased by 227.5%. In this study, an astaxanthin production model similar to H. pluvialis by combining carotenoid metabolism and fatty acid metabolism was constructed in C. reinhardtii. The results suggest that the increase in astaxanthin is indeed linked to the regulation of fatty acid metabolism, and this link may involve the type of fatty acids and the dynamics of astaxanthin ester in cells. The strategy of promoting the synthesis of fatty acids has potential to achieve efficient production of astaxanthin in C. reinhardtii.

BackgroundThe differences in short- and long-term outcome between laparoscopic liver resection (LLR) and open liver resection (OLR) for BCLC stage A large hepatocellular carcinoma (HCC) in difficult segments (I, IVa, VII, VIII) remain unclear. This PSM two-centre study aimed to compare perioperative and long-term survival outcomes of LLR with OLR for this HCC.MethodsHCC patients with BCLC stage A who underwent OLR or LLR in two medical centres were enrolled in the study. PSM analysis was performed to match patients between the LLR cohort and OLR cohort. Survival was analysed based on the Kaplan–Meier method. Independent risk factors were identified by Cox regression.ResultsAfter PSM, 35 patients remained in the LLR cohort, and 84 remained in the OLR cohort. Patients in the LLR cohort had more intraoperative blood loss (p=0.036) and shorter hospital stays after surgery (p

Summary: Branched-chain amino acids (BCAAs) provide nutrient signals for cell survival and growth. How BCAAs affect CD8+ T cell functions remains unexplored. Herein, we report that accumulation of BCAAs in CD8+ T cells due to the impairment of BCAA degradation in 2C-type serine/threonine protein phosphatase (PP2Cm)-deficient mice leads to hyper-activity of CD8+ T cells and enhanced anti-tumor immunity. CD8+ T cells from PP2Cm−/− mice upregulate glucose transporter Glut1 expression in a FoxO1-dependent manner with more glucose uptake, as well as increased glycolysis and oxidative phosphorylation. Moreover, BCAA supplementation recapitulates CD8+ T cell hyper-functions and synergizes with anti-PD-1, in line with a better prognosis in NSCLC patients containing high BCAAs when receiving anti-PD-1 therapy. Our finding thus reveals that accumulation of BCAAs promotes effector function and anti-tumor immunity of CD8+ T cells through reprogramming glucose metabolism, making BCAAs alternative supplementary components to increase the clinical efficacy of anti-PD-1 immunotherapy against tumors.

Oncolytic viruses (OVs), without harming normal tissues, selectively infect and replicate within tumor cells, to release immune molecules and tumor antigens, achieving immune-mediated destruction of tumors and making them one of the most promising immunotherapies for cancer. Many clinical studies have demonstrated that OVs can provide clinical benefits for patients with different types of tumors, at various stages, including metastatic and previously untreatable cases. When OVs are used in combination with chemotherapy, radiotherapy, immunotherapy, and other treatments, they can synergistically enhance the therapeutic effects. The concept of oncolytic virotherapy (OVT) was proposed in the early 20th century. With advancements in genetic engineering, genetically modified viruses can further enhance the efficacy of cancer immunotherapy. In recent years, global research on OV treatment of malignant tumors has increased dramatically. This article comprehensively reviews the findings from relevant research and clinical trials, providing an overview of the development of OVT and its application in the clinical treatment of head and neck cancer. The aim is to offer insights for future clinical and fundamental research on OVT.

The tung tree (Vernicia fordii Hemsl.), as a woody oilseed crop, has been cultivated in China for thousands of years, and its leaves are rich in cellulose and proteins. The tung leaf is an alternative raw material for the traditional ethanol fermentation of food crops. In this work, the effects of the simultaneous saccharification fermentation of tung leaves at different substrate concentrations on gas production characteristics, reducing sugars, pH, oxidation–reduction potential (ORP), and ethanol yield were investigated during bioethanol production. In addition, the effect of the initial fermentation pH on the ethanol fermentation of tung leaves was explored. The results showed that during bioethanol production from tung leaves, the pH of the fermentation broth showed a continuous decreasing trend. Moreover, the ORP showed a decreasing trend and then rebounded, and the concentration of reducing sugars initially increased and then decreased. The optimal ethanol yield of 4.99 g/L was obtained when the substrate concentration was 100 g/L. Changes in the initial pH have little effect on yeast activity, but such changes can affect the yeast cell wall structure and substance transport, leading to differences in the ethanol yield. When the initial pH is 7, the maximum ethanol yield is 5.22 g/L. The experimental results indicate that the utilization of tung leaves for bioethanol production has a good potential for development.

Our previous study showed that early supplementation with 10 g/(d·head) of galacto-oligosaccharides (GOS) in newborn Holstein dairy calves reduced the incidence of diarrhea and improved growth performance and mineral absorption. Since the dose of 10 g/(d·head) was the lowest by dose screening in our previous study, the present study was designed to investigate whether a lower amount of GOS has similar effects on growth performance, immune function, serum nutrients in newborn Holstein heifer calves, and to further investigate its effect on appetite-related hormones. Twenty-eight healthy newborn (1 day of age) Holstein heifers with similar average body weight (41.18 ± 1.90 kg) were randomly divided into four groups (n = 7): the control group (CON group), which received heated raw milk, and three experimental groups, which received heated raw milk supplemented with 2.5 (GOS2.5 group), 5 (GOS5 group), and 10 g/(d·head) (GOS10 group) GOS. All heifer calves were fed the same starter for 28 d. Supplementation with GOS linearly increased the final body weight, average daily gain, and feed efficiency in heifer calves (p < 0.01). Compared with the control group, the average daily gain and feed efficiency of heifer calves were significantly higher in the GOS5 and GOS10 groups than in the control group (p < 0.05). Furthermore, supplementation with GOS quadratically enhanced the starter and total average daily feed intake of the heifers (p < 0.01), especially in the GOS2.5 and GOS5 groups, (p < 0.05 vs. CON). The serum concentration of immunoglobulin A was linearly increased by GOS supplementation (p < 0.05), and the levels in the GOS5 and GOS10 groups were significantly higher than those in the CON group. Meanwhile, GOS linearly decreased serum interleukin-1β and interleukin-6 concentrations (p < 0.05). The serum concentration of triglycerides was also linearly decreased (p < 0.05), whereas total protein and blood urea nitrogen were linearly increased (p < 0.05). Supplementation with GOS linearly decreased the serum concentration of leptin (p < 0.05) but increased cholecystokinin and glucagon-like peptide-1 (p < 0.05). Increasing doses of GOS linearly improved serum calcium and copper concentrations (p < 0.01) and quadratically enhanced the concentration of magnesium, which peaked in the GOS5 group (p < 0.05). In conclusion, GOS supplementation reduced the incidence of diarrhea and improved the growth performance and immune function of Holstein heifer calves.

Persimmon fruit has a high nutritional value and significantly varies between pollination-constant astringent (PCA) and pollination-constant non-astringent (PCNA) persimmons. The astringency type affects sugar, flavonoids, and tannin accumulation and is well known in persimmon fruit. However, the impact of the fruit astringency type on ascorbic acid (AsA) accumulation is limited. In this study, typical PCA varieties (‘Huojing’ and ‘Zhongshi5’) and PCNA varieties (‘Yohou’ and ‘Jiro’) of persimmon fruit were sampled at four developing stages (S1–S4) to provide valuable information on AsA content variation in PCA and PCNA persimmon. Persimmon fruit is rich in ascorbic acid; the AsA content of the four varieties ‘Zhongshi5’, ‘Huojing’, ‘Jiro’, and ‘Youhou’ mature fruit reached 104.49, 48.69, 69.69, and 47.48 mg/100 g. Fruit of the same astringency type persimmon showed a similar AsA accumulation pattern. AsA content was significantly higher in PCA than PCNA fruit at S1–S3. The initial KEGG analysis of metabolites showed that galactose metabolism is the major biosynthetic pathway of AsA in persimmon fruit. There were significant differences in galactose pathway-related metabolite content in developing PCA and PCNA fruit, such as Lactose, D-Tagatose, and D-Sorbitol content in PCA being higher than that of PCNA. Combined gene expression and WGCNA analyses showed that the expression of the GME (evm.TU.contig4144.37) gene was higher in PCA-type than in PCNA-type fruit in S1–S3 and exhibited the highest correlation with AsA content (r = 690 **, p < 0.01). Four hub genes, including the DNA methylation gene, methyltransferase gene, F-box, and Actin-like Protein, were identified as potential regulators of the GME gene. These results provide basic information on how astringency types affect AsA accumulation and will provide valuable information for further investigation on AsA content variation in persimmon fruit.

Persimmons (Diospyros) are economically important trees that are widely cultivated for wood production in China, and Diospyros oleifera Cheng is the main persimmon grafting stock. However, an efficient tissue culture system has not been perfected for D. oleifera due to the limits of proliferation and rooting cultures. Therefore, this study examined the effects of different plant growth regulators and concentrations on the primary culture of young embryos, induction of leaf callus, differentiation of adventitious shoots, and rooting culture of D. oleifera. The optimal formula for young embryo germination was 1/2 Murashige and Skoog (MS) medium containing 0.5 mg/L gibberellic acid (GA3); after 25 days, the sprouting rate of the young embryos was 67.3%. The best medium for leaf callus induction was 1/2MS medium containing 2.0 mg/L of 6-benzylaminopurine (6-BA) and 0.5 mg/L of naphthaleneacetic acid (NAA), and the callus induction rate was 88.9%. Then, the callus was transferred to 1/2MS medium containing 2.0 mg/L of zeatin (ZT), 0.5 mg/L of NAA, and 2.0 mg/L of thidiazuron (TDZ) to induce adventitious shoots; after 25 days, 5.4 buds were produced per explant, and the induction rate of the adventitious shoots was 88.3%. The adventitious shoots were transferred to 1/2MS medium containing 2.0 mg/L of ZT, 2.0 mg/L of 6-(γ,γ-dimethylallylamino)purine (2iP), and 0.1 mg/L of indole acetic acid (IAA) for the proliferation culture, for which the multiplication coefficient approached 7.5. After multiplication, the adventitious shoots were inoculated into 1/2MS medium containing 1.0 mg/L of indole butyric acid (IBA), 0.5 mg/L of NAA, and 1.0 mg/L of kinetin (KT); the rooting rate was 60.2%, and the average number of roots was 6.9.

Continued mutation of the SARS-CoV-2 genome has led to multiple waves of COVID-19 infections, and new variants have continued to emerge and dominate. The emergence of Omicron and its subvariants has substantially increased the infectivity of SARS-CoV-2. RBD genes of the wild-type SARS-CoV-2 strain and the Delta, Omicron BA.1 and Omicron BA.2 variants were used to construct plasmids and express the proteins in glycoengineered Pichia pastoris. A stable 4 L-scale yeast fermentation and purification process was established to obtain high-purity RBD proteins with a complex glycoform N-glycosyl structure that was fucose-free. The RBD glycoproteins were combined with two adjuvants, Al(OH)3 and CpG, which mitigated the typical disadvantage of low immunogenicity associated with recombinant subunit vaccines. To improve the broad-spectrum antiviral activity of the candidate vaccine, Delta RBD proteins were mixed with BA.2 RBD proteins at a ratio of 1:1 and then combined with two adjuvants—Al(OH)3 and CpG—to prepare a bivalent vaccine. The bivalent vaccine effectively induced mice to produce pseudovirus-neutralizing antibodies against SARS-CoV-2 variants, Delta, Beta, and Omicron sublineages BA.1, BA.2, BA.5. The bivalent vaccine could neutralize the authentic wild-type SARS-CoV-2 strain, Delta, BA.1.1, BA.2.2, BA2.3, and BA.2.12.1 viruses, providing a new approach for improving population immunity and delivering broad-spectrum protection under the current epidemic conditions.

As an important component of new energy vehicles, the safety of lithium-ion batteries has attracted extensive attention. To reveal the mechanism and characteristics of ternary lithium-ion batteries under different trigger modes, an experimental system was established. The effects of different trigger modes on battery surface temperature, battery internal temperature, injection time, and battery voltage were analyzed. Among them, acupuncture, overheating, and overcharging are used as trigger conditions for mechanical, thermal, and electrical abuse. The results show that the injection time and surface peak temperature are positively correlated with the energy input before thermal runaway. Before the cell triggers abuse, the more input energy, the higher the cell surface temperature, the more serious the thermal runaway, and the higher the damage to the surrounding battery system. Under the same conditions, the intensity and damage degree of overcharge thermal runaway are greater than those of internal short circuit and overtemperature. The abnormal change of voltage suddenly rising and rapidly falling can be used as a condition to judge whether overcharge thermal runaway occurs. Finally, according to the temperature curves at different positions, the thermal diffusion law under different abuse conditions is summarized, which provides a basis for the safety design of the battery module.

Research on fire detection based on deep learning has been increasing lately, and current models differ in accuracy and computational complexity. To reduce the loss of semantic information and improve prediction accuracy, this paper combines dynamic threshold grayscale segmentation and residual network transfer learning. An effective training data extension strategy integrates the experimental data of a real fire platform and a forest-image-based fire database, where the experimental data of the real fire platform are shot based on different lighting and backgrounds. It has been proven that this is a good solution that can effectively solve the problem of training robust deep models relying on datasets with large diversity, which can improve the overall performance of the training model. Then, we introduce a network architecture based on dynamic threshold grayscale segmentation and residual net transfer learning, which reaches residual net level accuracy on image-based fire detection tasks with less computation. We train the model with a self-built image dataset, test it on a general fire image dataset, and evaluate it on a self-built fire video dataset. In numerous experiments, our method produced a training and testing accuracy of 98.26% and 99.90%, respectively, with corresponding losses of 0.036 and 0.04. The evaluation accuracy was 90% under the condition of a complex sample environment. Compared with other models, our method has advantages in accuracy, training loss, and cost time. Comprehensive comparisons show effectiveness and improved overall performance.