Transcriptomic and metabolomic profiling provide insight into the role of sugars and hormones in leaf senescence of Pinellia ternata.

KEY MESSAGE: The interaction network and pathway map uncover the potential crosstalk between sugar and hormone metabolisms as a possible reason for leaf senescence in P. ternata. Pinellia ternata, an environmentally sensitive medicinal plant, undergoes leaf senescence twice a year, affecting its development and yield. Understanding the potential mechanism that delays leaf senescence could theoretically decrease yield losses. In this study, a typical senescent population model was constructed, and an integrated analysis of transcriptomic and metabolomic profiles of P. ternata was conducted using two early leaf senescence populations and two stay-green populations. The result showed that two key gene modules were associated with leaf senescence which were mainly enriched in sugar and hormone signaling pathways, respectively. A network constructed by unigenes and metabolisms related to the obtained two pathways revealed that several compounds such as D-arabitol and 2MeScZR have a higher significance ranking. In addition, a total of 130 hub genes in this network were categorized into 3 classes based on connectivity. Among them, 34 hub genes were further analyzed through a pathway map, the potential crosstalk between sugar and hormone metabolisms might be an underlying reason of leaf senescence in P. ternata. These findings address the knowledge gap regarding leaf senescence in P. ternata, providing candidate germplasms for molecular breeding and laying theoretical basis for the realization of finely regulated cultivation in future.

Direct Growth of a Polymer Film to Induce Horizontal Orientation of Zn4(OH)6SO4·xH2O for Stable Zn Metal Batteries.

The loose and randomly oriented byproduct (i.e., Zn4(OH)6SO4·xH2O, ZHS) in situ formed on the zinc (Zn) surface is recognized to be the primary cause for dendritic Zn growth and side reactions. Switching the detrimental passivation film into a dense and kinetically favorable solid electrolyte interphase (SEI) is a straightforward strategy to tackle these issues faced by Zn metal anodes but remains largely unexplored. Herein, a new polymer film directly grown on Zn metal through room-temperature plasma-enhanced chemical vapor deposition is proposed to induce the lateral growth of ZHS nanosheets and decrease the Zn2+ desolvation barrier, thereby forming a beneficial composite SEI for suppressing Zn dendrite growth and surface corrosion. As a result of the joint effect, we realize an impressively stable cycling behavior in symmetric cell over 3400 h at 2 mA cm-2. Moreover, full cells also demonstrate prolonged lifespans. This work opens a new avenue for stabilizing Zn metal batteries by turning detrimental ZHS into a favorable interlayer.

Suppressing Zn pulverization with three-dimensional inert-cation diversion dam for long-life Zn metal batteries.

Tremendous attention has been paid to the water-associated side reactions and zinc (Zn) dendrite growth on the electrode-electrolyte interface. However, the Zn pulverization that can cause continuous depletion of active Zn metal and exacerbate hydrogen evolution is severely neglected. Here, we disclose that the excessive Zn feeding that causes incomplete crystallization is responsible for Zn pulverization formation through analyzing the thermodynamic and kinetics process of Zn deposition. On the basis, we introduce 1-ethyl-3-methylimidazolium cations (EMIm+) into the electrolyte to form a Galton-board-like three-dimensional inert-cation (3DIC) region. Modeling test shows that the 3DIC EMIm+ can induce the Zn2+ flux to follow in a Gauss distribution, thus acting as elastic sites to buffer the perpendicular diffusion of Zn2+ and direct the lateral diffusion, thus effectively avoiding the local Zn2+ accumulation and irreversible crystal formation. Consequently, anti-pulverized Zn metal deposition behavior is achieved with an average Coulombic efficiency of 99.6% at 5 mA cm-2 over 2,000 cycles and superb stability in symmetric cell over 1,200 h at -30 °C. Furthermore, the Zn||KVOH pouch cell can stably cycle over 1,200 cycles at 2 A g-1 and maintain a capacity of up to 12 mAh.

Intestinal metabolite UroB alleviates cerebral ischemia/reperfusion injury by promoting competition between TRIM65 and TXNIP for binding to NLRP3 inflammasome in response to neuroinflammation.

Our previous research suggests that targeting NLRP3 inflammasomes holds promise for mitigating cerebral ischemia/reperfusion injury. The gut metabolite Urolithin B (UroB) has been shown to inhibit the neuroinflammation. However, the specific role of UroB in cerebral ischemia/reperfusion injury and its potential impact on NLRP3 inflammasome remain unclear. In this study, acute stroke was simulated using the MCAO model in male Sprague-Dawley rats. UroB was intraperitoneally administered after 1 h of reperfusion. The effects of UroB on brain tissue were evaluated, including infarct volume, brain edema, and neurobehavioral changes. Western blotting and immunofluorescence were performed to investigate the effect of UroB on inflammation-related proteins. Furthermore, TRIM65 knockdown and TXNIP overexpression experiments elucidated the role of UroB in NLRP3 inflammasome activation. The ( demonstrate the neuroprotective effect of UroB in acute stroke, reducing brain tissue damage and improving motor function. Mechanistically, UroB modulated neuroinflammation by influencing TXNIP and TRIM65 protein expression, as well as competitive binding to the NLRP3 inflammasome, attenuating cerebral ischemia/reperfusion injury. In conclusion, the potential of UroB as a protective agent against cerebral ischemia/reperfusion injury in acute stroke stands out as it regulates TRIM65 and TXNIP competitive binding to the NLRP3 inflammasome. These findings suggest that UroB is a promising drug candidate for the treatment of acute stroke.

Construction of a three-dimensional inflammation model of human bronchial epithelial cells BEAS-2B by using the self-assembling D-form peptide Sciobio-â ¢.

Human bronchial epithelial cells in the airway system, as the primary barrier between humans and the surrounding environment, assume a crucial function in orchestrating the processes of airway inflammation. Target to develop a new three-dimensional (3D) inflammatory model to airway system, and here we report a strategy by using self-assembling D-form peptide to cover the process. By testing physicochemical properties and biocompatibility of Sciobio-Ⅲ, we confirmed that it can rapidly self-assembles under the trigger of ions to form a 3D nanonetwork-like scaffold, which supports 3D cell culture including the cell strains like BEAS-2B cells. Subsequently, inflammation model was established by lipopolysaccharide (LPS), the expression of some markers of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interleukin-8 (IL-8), the levels of relevant inflammatory factors were measured by RT-qPCR and the secretion profile of inflammatory cytokines by ELISA, are obtained the quite difference effects in 2D and 3D microenvironment, which suggested Sciobio-Ⅲ hydrogel is an ideal scaffold that create the microenvironment for 3D cell culture. Here we are success to establish a 3D inflammation model for airway system. This innovative model allows for rapid and accurate evaluation of drug metabolism and toxicological side effects, hope to use in drug screening for airway inflammatory diseases and beyond.

Transcriptome Sequencing and Mass Spectrometry Reveal Genes Involved in the Non-mendelian Inheritance-Mediated Feather Growth Rate in Chicken.

The feather growth rate in chickens included early and late feathering. We attempted to characterize the genes and pathways associated with the feather growth rate in chickens that are not in agreement with Mendelian inheritance. Gene expression profiles in the hair follicle tissues of late-feathering cocks (LC), early-feathering cocks (EC), late-feathering hens (LH), and early-feathering hens (EH) were acquired using RNA sequencing (RNA-seq), mass spectrometry (MS), and quantitative reverse transcription PCR (qRT­PCR). A total of 188 differentially expressed genes (DEGs) were ascertained in EC vs. LC and 538 DEGs were identified in EH vs. LH. We observed that 14 up-regulated genes and 9 down-regulated genes were screened both in EC vs. LC and EH vs. LH. MS revealed that 41 and 138 differentially expressed proteins (DEPs) were screened out in EC vs. LC and EH vs. LH, respectively. Moreover, these DEGs and DEPs were enriched in multiple feather-related pathways, including JAK-STAT, MAPK, WNT, TGF-ß, and calcium signaling pathways. qRT-PCR assay showed that the expression of WNT8A was decreased in LC compared with EC, while ALK and GRM4 expression were significantly up-regulated in EH relative to LH. This study helps to elucidate the potential mechanism of the feather growth rate in chickens that do not conform to genetic law.

Engineering Self-Assembling Peptide Hydrogel to Enhance the Capacity of Dendritic Cells to Activate In Vivo T-Cell Immunity.

The efficacy of the dendritic cell (DC) has failed to meet expectations thus far, and crucial problems such as the immature state of DCs, low targeting efficiency, insufficient number of dendritic cells, and microenvironment are still the current focus. To address these problems, we developed two self-assembling peptides, RLDI and RQDT, that mimic extracellular matrix (ECM). These peptides can be self-assembled into highly ordered three-dimensional nanofiber scaffold structures, where RLDI can form gelation immediately. In addition, we found that RLDI and RQDT enhance the biological function of DCs, including releasing antigens sustainably, adhering to DCs, promoting the maturation of DCs, and increasing the ability of DC antigen presentation. Moreover, peptide hydrogel-based DC treatment significantly achieved prophylactic and treatment effects on colon cancer. These results have certain implications for the design of new broad-spectrum vaccines in the future.

Causal associations of thyroid function and sudden sensorineural hearing loss: a bidirectional and multivariable Mendelian randomization study.

Background: Observational studies have indicated a potential association between thyroid dysfunction and the risk of sudden sensorineural hearing loss (SSNHL). However, the precise causal relationship between the two remains uncertain. The objective of our study was to assess the causal influence of thyroid function on SSNHL by employing a bidirectional and multivariable Mendelian randomization (MR) approach. Methods: Single-nucleotide polymorphisms (SNPs) associated with free thyroid (FT4) and thyroid stimulating hormone (TSH) were selected from the summary data of a large genome-wide association study (GWAS) conducted on European individuals. The summary-level data of SSNHL were also obtained from a GWAS, which included 196,592 participants (1,491 cases and 195,101 controls). The MR analysis primarily utilized the inverse variance weighted (IVW) method, with sensitivity analyses performed using the weighted median, MR-Egger, and MR-PRESSO approaches. Results: In the IVW method, an elevated genetically predicted FT4 level was found to effectively reduce the risk of SSNHL (OR = 0.747, 95% CI = 0.565-0.987, P = 0.04). These findings were consistent when conducting multivariate MR analysis, which adjusted for TSH levels (OR = 0.929, 95% CI = 0.867-0.995, P = 0.036). However, genetically predicted TSH levels did not emerge as a risk factor for SSNHL (OR = 1.409, 95% CI = 0.895-1.230, P = 0.547). Furthermore, even after adjusting for FT4 levels in the multivariate MR analysis, no evidence of a direct causal relationship between TSH levels and the risk of SSNHL was observed (OR = 1.011, 95% CI = 0.880-1.161, P = 0.867). The reverse MR analysis showed that there was no evidence of a direct causal relationship between SSNHL and the risk of FT4 level (OR = 1.026, 95% CI = 0.999-1.054, P = 0.056) or TSH level (OR = 1.002, 95% CI = 0.989-1.015, P = 0.702). Conclusion: Within the normal range, genetic variants associated with higher FT4 levels demonstrate a potential protective effect against SSNHL, whereas there is no direct causal relationship between TSH levels and the risk of SSNHL.

Evidence for early domestic yak, taurine cattle, and their hybrids on the Tibetan Plateau.

Domestic yak, cattle, and their hybrids are fundamental to herder survival at high altitudes on the Tibetan Plateau. However, little is known about their history. Bos remains are uncommon in this region, and ancient domestic yak have not been securely identified. To identify Bos taxa and investigate their initial management, we conducted zooarchaeological analyses of 193 Bos specimens and sequenced five nuclear genomes from recently excavated assemblages at Bangga. Morphological data indicated that more cattle than yak were present. Ancient mitochondrial DNA and nuclear genome sequences identified taurine cattle and provided evidence for domestic yak and yak-cattle hybridization ~2500 years ago. Reliance on diverse Bos species and their hybrid has increased cattle adaptation and herder resilience to plateau conditions. Ancient cattle and yak at Bangga were closely related to contemporary livestock, indicating early herder legacies and the continuity of cattle and yak husbandry on the Tibetan Plateau.

Global genetic diversity, introgression, and evolutionary adaptation of indicine cattle revealed by whole genome sequencing.

Indicine cattle, also referred to as zebu (Bos taurus indicus), play a central role in pastoral communities across a wide range of agro-ecosystems, from extremely hot semiarid regions to hot humid tropical regions. However, their adaptive genetic changes following their dispersal into East Asia from the Indian subcontinent have remained poorly documented. Here, we characterize their global genetic diversity using high-quality whole-genome sequencing data from 354 indicine cattle of 57 breeds/populations, including major indicine phylogeographic groups worldwide. We reveal their probable migration into East Asia was along a coastal route rather than inland routes and we detected introgression from other bovine species. Genomic regions carrying morphology-, immune-, and heat-tolerance-related genes underwent divergent selection according to Asian agro-ecologies. We identify distinct sets of loci that contain promising candidate variants for adaptation to hot semi-arid and hot humid tropical ecosystems. Our results indicate that the rapid and successful adaptation of East Asian indicine cattle to hot humid environments was promoted by localized introgression from banteng and/or gaur. Our findings provide insights into the history and environmental adaptation of indicine cattle.

Regulating interfacial reaction through electrolyte chemistry enables gradient interphase for low-temperature zinc metal batteries.

In situ formation of a stable interphase layer on zinc surface is an effective solution to suppress dendrite growth. However, the fast transport of bivalent Zn-ions within the solid interlayer remains very challenging. Herein, we engineer the SEI components and enable superior kinetics of Zn metal batteries under harsh conditions through regulating the sequence of interfacial chemical reaction. With the differences in chemical reactivity of trimethyl phosphate co-solvent and trifluoromethanesulfonate anions in the Zn2+-solvation shell, Zn3(PO4)2 and ZnF2 are successively generated on Zn metal surface to form a gradient ZnF2-Zn3(PO4)2 interphase. Mechanistic studies reveal the outer ZnF2 facilitates Zn2+ desolvation and inner Zn3(PO4)2 serves as channels for fast Zn2+ transport, contributing to long-term cycling at subzero temperatures. Impressively, the gradient SEI enables a high lifespan over 7000 hours in Zn symmetric cell and a capacity retention of 86.1% after 12000 cycles in Zn-KVOH full cell at -50 °C.

Comparative and phylogenetic analysis of complete chloroplast genome sequences of Salvia regarding its worldwide distribution.

Salvia is widely used as medicine, food, and ornamental plants all over the world, with three main distribution centers, the Central and western Asia/Mediterranean (CAM), the East Aisa (EA), and the Central and South America (CASA). Along with its large number of species and world-wide distribution, Salvia is paraphyletic with multiple diversity. Chloroplast genomes (CPs) are useful tools for analyzing the phylogeny of plants at lower taxonomic levels. In this study, we reported chloroplast genomes of five species of Salvia and performed phylogenetic analysis with current available CPs of Salvia. Repeated sequence analysis and comparative analysis of Salvia CPs were also performed with representative species from different distribution centers. The results showed that the genetic characters of the CPs are related to the geographic distribution of plants. Species from CAM diverged first to form a separate group, followed by species from EA, and finally species from CASA. Larger variations of CPs were observed in species from CAM, whereas more deficient sequences and less repeated sequences in the CPs were observed in species from CASA. These results provide valuable information on the development and utilization of the worldwide genetic resources of Salvia.

The genetic secrets of adaptation: decoding the significance of the 30-bp insertion in the KRT77 gene for Chinese cattle.

The KRT77 gene is a type II epithelial cell α-keratin gene family member that plays a crucial role in animal epidermal and coat formation. This study aimed to investigate the relationship between the KRT77 gene and the adaptability of Chinese cattle in varying environments by exploring the distribution of an exon insertion of the KRT77 gene in different cattle populations. Our analysis involved amplifying and sequencing DNA samples from 362 individuals from 24 cattle breeds in China. Our findings reveal a gradual increase in the frequency of insertion from the northwest to the southeast population. We conducted an association analysis between the genotypes and climate data, revealing a correlation between the insertion and local annual mean temperature, relative humidity, and temperature humidity index. The study highlights the significance of the newly identified KRT77 gene insertion as a variation associated with environmental adaptation in Chinese cattle.This insertion variation increased insights into the genetic mechanisms that drive adaptation in Chinese cattle, emphasizing the importance of the 30-bp insertion in the KRT77 gene. Our findings facilitate further research to improve cattle breeding strategies for adaptability to changing environments from the northwest to the southeast population. In conclusion, this study provides value.

Surgical treatment and functional outcome of bilateral symmetrical hip dislocation and Pipkin type II femoral head fracture: a 5-year follow-up case report and literature review.

Background: Bilateral posterior hip dislocation and femoral head fracture are rare injuries, which may be the earliest case report that focuses on treatment with open reduction via the direct anterior approach (DAA) for bilateral symmetrical Pipkin type II fracture within 5 years of the follow-up period. Case report: We present a case of bilateral posterior dislocation with a femoral head fracture (Pipkin II) of the hip in 47-year-old woman caused by a high-velocity accident. The dislocation was successfully reduced under general anesthesia at a local hospital and transferred to a tertiary center for surgical management. She was surgically treated with internal fixation using three Herbert screws on the bilateral hips. The DAA was used during surgery. Follow-up for 5 years was performed, and functional outcomes were evaluated using the D'Aubigné range of motion and modified Harris hip score. The range of motion in the bilateral hip was satisfactory, with no signs of post-traumatic arthritis, heterotopic ossification, or avascular necrosis of the femoral head. Conclusion: Surgical management of bilateral Pipkin type II fractures was performed successfully with open reduction and internal fixation using a safe and reliable direct anterior approach, with good functional outcomes at 5-year follow-up.

A disposable impedance-based sensor for in-line cell growth monitoring in CAR-T cell manufacturing.

This paper presents the development of low-cost, disposable impedance-based sensors for real-time, in-line monitoring of suspension cell culture. The sensors consist of electrical discharge machining (EDM) cut aluminum electrodes and polydimethylsiloxane (PDMS) spacers, both of which are low-cost materials that can be safely disposed of. Our research demonstrates the capability of these low-cost sensors for in-line, non-invasive monitoring of suspension cell growth in cell manufacturing. We use a hybrid equivalent circuit model to extract key features/parameters from intertwined impedance signals, which are then fed to a novel physics-inspired (gray-box) model designed for α-relaxation. This model determines viable cell count (VCC), a critical quality attribute (CQA) in cell manufacturing. Predicted VCC trends are then compared with image-based cell count data to verify their accuracy.

Physiological and transcriptional responses to heat stress in a typical phenotype of Pinellia ternata.

Pinellia ternata is an important medicinal plant, and its growth and development are easily threatened by high temperature. In this study, comprehensive research on physiological, cytological and transcriptional responses to different levels of heat stress were conducted on a typical phenotype of P. ternata. First, P. ternata exhibited tolerance to the increased temperature, which was supported by normal growing leaves, as well as decreased and sustained photosynthetic parameters. Severe stress aggravated the damages, and P. ternata displayed an obvious leaf senescence phenotype, with significantly increased SOD and POD activities (46% and 213%). In addition, mesophyll cells were seriously damaged, chloroplast thylakoid was fuzzy, grana lamellae and stroma lamellae were obviously broken, and grana thylakoids were stacked, resulting in a dramatically declined photosynthetic rate (74.6%). Moreover, a total of 16 808 genes were significantly differential expressed during this process, most of which were involved in photosynthesis, transmembrane transporter activity and plastid metabolism. The number of differentially expressed transcription factors in MYB and bHLH families was the largest, indicating that these genes might participate in heat stress response in P. ternata. These findings provide insight into the response to high temperature and facilitate the standardized cultivation of P. ternata.

Management and outcome of patients with femoral head fractures: the mid-term follow-up with injuries and associated prognostic factors.

BACKGROUND: Femoral head fractures are rare injuries often associated with poor functional outcomes and complications. The purpose of this study was to evaluate the incidence, treatment methods and approaches, complications, and functional outcomes of femoral head fractures. METHODS: We retrospectively reviewed 50 patients who sustained femoral head fractures between January 2011 and December 2018. There were thirty-seven (74%) males and thirteen (26%) females with a median age of 40 years. According to Pipkin's classification, there were eighteen (36%) Pipkin I, ten (20%) Pipkin II, eight (16%) Pipkin III, and fourteen (28%) Pipkin IV patients. Treatment methods were categorized into non-operative, operative by open reduction and internal fixation (ORIF), and immediate total hip replacement (THR). The recorded surgical approach consists of an anterior(S-P) approach, posterior(K-L) approach, lateral stab, and combined anterior + lateral stab approach for fixation. The patients were also stratified by the Injury Severity Score (ISS), associated injuries, and, mechanism of injuries. The modified harris hip score (MHHS) was used to evaluate the ongoing complications with the clinical outcome of patients with two years or greater follow-up. RESULTS: Eight (16%) patients were managed successfully with closed reduction without surgery and thirty-seven (74%) patients required operative reduction and internal fixation (ORIF) of the femoral head and acetabulum, and 5 (10%) patients required immediate THR. Six (12%) patients developed AVN, and four (8%) required a secondary THR. Sixteen patients (33%) developed post-traumatic osteoarthritis (PTOA), eight (16%) developed heterotopic ossification (HO) and six patients (12%) had sciatic nerve injury, none requiring operative treatment. Overall functional results according to MHHS were, excellent in two (4%) patients, good in sixteen (32%) patients, fair in twenty-two (44%) patients, and poor in ten (20%) patients. A statistically significant difference in outcome was observed among four pipkin subtypes. CONCLUSION: Femoral head fractures are rare injuries often associated with poor outcomes. In this study, we report the functional outcomes and complications of all treatment approaches for femoral head fracture based on the Pipkin classification. The treatment aim should always be the anatomical reduction of the fragments. This study, adds to the growing literature on femoral head fracture and provides a reference for the clinical treatment to guide patient management. TRIAL REGISTRATION: Our study was approved by the Clinical Research and Biomedical Ethical Committee of West China Hospital, Sichuan University, and was performed in accordance with the Declaration of Helsinki. All participants provided written informed consent to participate in this study.

A missense mutation of the WNK1 gene affects cold tolerance in Chinese domestic cattle.

Inclement weather conditions, especially cold stress, have threatened the cattle industry. Cattle exposed to cold environments for a longer time suffer developmental delay, immunity decline, and eventually death. WNK1 is a member of With-no-lysine kinases (WNKs), widely expressed in animal organs and tissues. WNK1 and WNK4 are expressed in adipose tissue, and WNK4 promotes adipogenesis. WNK1 does not directly affect adipogenesis but has been shown to promote WNK4 expression in several tissues or organs. One missense mutation NC_037346.1:g.107692244, A > G, rs208265410 in the WNK1 gene was detected from the database of bovine genomic variation (BGVD). Here, we collected 328 individuals of 17 breeds representing four groups of Chinese cattle, northern group cattle, southern group cattle, central group cattle, and special group cattle (Tibetan cattle). We also collected the temperature and humidity data records from their relative locations. The frequencies of the G allele in Chinese breeds increased from northern China to southern China, and the frequencies of the A allele showed an opposite trend. Our results indicate that the WNK1 gene might be a candidate gene marker associated with cold tolerance.

Genome-wide analysis emancipates genomic diversity and signature of selection in Altay white-headed cattle of Xinjiang, China.

Altay white-headed cattle have not received enough attention for several reasons. Due to irrational breeding and selection practices, the number of pure Altay white-headed cattle has decreased significantly and the breed is now on the eve of extinction. The genomic characterization will be a crucial step towards understanding the genetic basis of productivity and adaptability to survival under native Chinese agropastoral systems; nevertheless, no attempt has been made in Altay white-headed cattle. In the current study, we compared the genomes of 20 Altay white-headed cattle to the genomes of 144 individuals in representative breeds. Population genetic diversity revealed that the nucleotide diversity of Altay white-headed cattle was less than that of indicine breeds and comparable to that of Chinese taurus cattle. Using population structure analysis, we also found that Altay white-headed cattle carried the ancestry of the European and East Asian cattle lineage. In addition, we used three different methods (F ST, θπ ratio and XP-EHH) to investigate the adaptability and white-headed phenotype of Altay white-headed cattle and compared it with Bohai black cattle. We found EPB41L5, SCG5 and KIT genes on the list of the top one percent genes, these genes might have an association with environmental adaptability and the white-headed phenotype for this breed. Our research reveals the distinctive genomic features of Altay white-headed cattle at the genome-wide level.