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Dry aging is an effective method to improve the quality and value of meat. Meat quality characteristics such as tenderness and flavor can be significantly improved through a series of biochemical reactions. In recent years, dry-aged beef has gained huge popularity among consumers and research attention due to its unique flavor. However, there are some problems with the dry-aged beef industry, such as large quality differences, high losses during maturation, and high production costs. This article systematically summarizes quality characteristics of dry-aged beef, including flavor, tenderness, safety, color and water-holding capacity (WHC). The mechanism of formation of its characteristic flavor is briefly described. The effects of different dry-aging conditions on beef quality are summarized. New dry aging technologies and value-added ways to reuse the crust are introduced. This article will hopefully provide theoretical guidance for the standardized, efficient and high-value development of the dry-aged beef industry.

Abstract Background Circular RNAs (circRNAs) are closely associated with the development of breast cancer (BC). In this study, we aimed to clarify how differentially expressed circRNAs affect the development of BC. Methods Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to detect the expression of circADAM9, miR‐1236‐3p and fibroblast growth factor 7 (FGF7). Colony formation, 5‐ethynyl‐2′‐deoxyuridine (EdU), wound healing, transwell, and flow cytometry were used to assess cell proliferation, migration, invasion, and apoptosis. Glucose consumption, lactic acid production and ATP levels were assessed using glycolysis metabolism analysis. Dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay were carried out to verify the relationship between miR‐1236‐3p and circADAM9 or FGF7. The roles of cirADAM9 on tumor growth were analyzed using a xenograft tumor model. Ki‐67 and FGF7 expression was measured via immunohistochemistry (IHC) assay. Apoptosis‐related proteins and exosome markers were detected by western blot. Results CircADAM9 was highly expressed in BC cells, and circADAM9 silencing inhibited BC cell proliferation, migration, invasion, and glycolysis, and promoted cell apoptosis. Furthermore, miR‐1236‐3p inhibition could overturn circADAM9 knockdown‐mediated BC inhibition. Moreover, the negative influences of miR‐1236‐3p overexpression on BC progression were restrained via FGF7 overexpression. CircADAM9 silence also inhibited BC tumor growth in vivo. Conclusion CircADAM9 promoted BC development partly by the miR‐1236‐3p/FGF7 axis, highlighting a potential prognostic biomarker and therapeutic target for BC patients.

Abstract MRGPRX1, a Mas-related GPCR (MRGPR), is a key receptor for itch perception and targeting MRGPRX1 may have potential to treat both chronic itch and pain. Here we report cryo-EM structures of the MRGPRX1-Gi1 and MRGPRX1-Gq trimers in complex with two peptide ligands, BAM8-22 and CNF-Tx2. These structures reveal a shallow orthosteric pocket and its conformational plasticity for sensing multiple different peptidic itch allergens. Distinct from MRGPRX2, MRGPRX1 contains a unique pocket feature at the extracellular ends of TM3 and TM4 to accommodate the peptide C-terminal “RF/RY” motif, which could serve as key mechanisms for peptidic allergen recognition. Below the ligand binding pocket, the G6.48XP6.50F6.51G6.52X(2)F/W6.55 motif is essential for the inward tilting of the upper end of TM6 to induce receptor activation. Moreover, structural features inside the ligand pocket and on the cytoplasmic side of MRGPRX1 are identified as key elements for both Gi and Gq signaling. Collectively, our studies provide structural insights into understanding itch sensation, MRGPRX1 activation, and downstream G protein signaling.

Abstract Background To assess the predictive values of primary tumor FDG uptake for patients with inoperable stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT). Methods A total of 107 patients with diagnosis of stage III NSCLC and CCRT were enrolled. The tumor maximum uptake value (SUVmax) was standardized by calculating several ratios between tumor and each background tissues. The receiver operating characteristics curve (ROC) was used to compare the predictive power of prognostic models. The tumor objective response rate (ORR) and overall survival (OS) were compared and analyzed by the Kaplan–Meier method and univariate and multivariate Cox regression models. Results The areas under ROC curve (AUCs) ranged from 0.72 to 0.81 among these tumor SUVmax and standardized SUVmax ratios, and the tumor SUVmax and tumor SUVmax-to-liver SUVmean ratio (TLMR) were more predictive of ORR (AUC, 0.81; 95% CI, 0.73–0.88 for tumor SUVmax and AUC, 0.84; 95%CI, 0.76–0.91 for TLMR) than any of other SUVmax ratios. The patients with lower tumor SUVmax, SUVmean and SUVmax ratios had a significantly better OS than those with their corresponding higher ones. Moreover, both univariate and multivariable analyses revealed that TLMR was significantly associated with better ORR and OS after adjustment with other prognostic variables. Conclusions TLMR, a standardized tumor SUVmax, was an independent prognostic predictor for tumor ORR and OS of patients with stage III NSCLC after CCRT.

Abstract Purpose To investigate the feasibility and clinical utility of a compressed-sensing-accelerated subtractionless whole-body MRA (CS-WBMRA) protocol with only contrast injection for suspected arterial diseases, by comparison to conventional dual-pass subtraction-based whole-body MRA (conventional-WBMRA) and available computed tomography angiography (CTA). Materials and methods This prospective study assessed 86 patients (mean age, 56 years ± 16.4 [standard deviation]; 25 women) with suspected arterial diseases from May 2021 to December 2022, who underwent CS-WBMRA (n = 48, mean age, 55.9 years ± 16.4 [standard deviation]; 25 women) and conventional-WBMRA (n = 38, mean age, 48 years ± 17.4 [standard deviation]; 20 women) on a 3.0 T MRI after random group assignment based on the chronological order of enrolment. Of all enrolled patients administered the CS-WBMRA protocol, 35% (17/48) underwent CTA as required by clinical demands. Two experienced radiologists independently scored the qualitative image quality and venous enhancement contamination. Quantitative image assessment was carried out by determining and comparing the apparent signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of four representative arterial segments. The total examination time and contrast-dose were also recorded. The independent samples t-test or the Wilcoxon rank sum test was used for statistical analysis. Results The overall scores of CS-WBMRA outperformed those of conventional-WMBRA (3.40 ± 0.60 vs 3.22 ± 0.55, P 0.05) between the two protocols. In the quantitative analysis, overall apparent SNRs were significantly higher in the conventional-WBMRA group than in the CS-WBMRA group (214.98 ± 136.05 vs 164.90 ± 118.05; P 0.05). In the CS-WBMRA group, 7 of 1776 (0.4%) vessel segments were contaminated severely by venous enhancement, while in the convention-WBMRA group, 317 of 1406 (23%) were rated as severe contamination. In the CS-WBMRA group, total examination and reconstruction times were only 7 min and 10 min, respectively, vs 20 min and

Abstract Background Civilian nurses have gradually become the main body of military nurses. Our study aimed to understand their occupational happiness and its influencing factors. Methods This descriptive study was conducted with 319 civilian nurses working in 15 military hospitals in China. Based on literature review, expert consultation and combined with the characteristics of civilian positions, this study developed a questionnaire on occupational happiness of civilian nurses in military hospitals. The questionnaire includes 7 dimensions as follows: work emotion, salary, work environment, professional identity, work output, interpersonal relationship, well‑being. The demographic questionnaire and occupational well-being questionnaire of civilian nurses in military hospitals were analysed by t-test, analysis of variance and Pearson correlation analysis. Results The occupational happiness score (3.83 ± 0.56, upper limit score: 5) was at the upper middle level. There were significant differences in occupational well-being by gender (t = -2.668, p = 0.008), age (F = 5.085, p = 0.007) and the type of city where the hospital was located (F = 15.959, p

The current research on 7-series aluminum alloys mainly focuses on solid solution and aging treatments, as well as the flow stress during the deformation process. There are limited researches on the influence of thermal deformation temperature on the microstructure and properties of the aluminum alloy during multi-pass hot rolling process. In this study, the as-cast 7A04 aluminum alloy was subjected to homogenization treatment, followed by multi-pass hot rolling. The effects of different deformation parameters on dislocation density were analyzed. Microstructural characterization of the deformed alloy was performed using optical microscopy (OM), scanning electron microscopy (SEM) with energy-dispersive spectroscopy (EDS), X-ray diffraction (XRD), and micro-hardness tester. The optimal microstructure of the deformed alloy was selected based on the size of recrystallization. Subsequently, the Deform–3D finite element simulation software was used to analyze the multi-pass hot rolling process. The influence of deformation parameters on the uniformity of equivalent strain distribution within the samples was investigated. The results showed that at the deformation temperature of 430 °C, a significant amount of recrystallized microstructure appeared in the alloy, resulting in the lowest dislocation density and a significant reduction in the quantity of coarse precipitates. Finite element numerical simulation revealed that the deformation temperature had a certain influence on the uniformity of strain distribution within the alloy. However, this influence was mostly eliminated when the deformation temperature exceeded 380 °C. Meanwhile, the distribution of strain within the alloy was found to be related to the temperature distribution.

Abstract Background Aspartoacylase (ASPA) is a gene that plays an important role in the metabolic reprogramming of cancer. However, the clinical relevance of ASPA in gastric cancer (GC) has not been demonstrated. Methods The link between ASPA and the clinical features of GC was determined using two public genomic databases. The multivariate Cox proportional hazard model and generalised linear regression model were applied to examine whether the ASPA level is associated with the prognosis and other pathological factors. In addition, the role of specific genes in the infiltration of immune cells in the setting of GC was investigated using a further immunological database. The expression level of various proteins was detected using a western blotting assay. Transwell and methyl thiazolyl tetrazolium tests were applied for the detection of cellular invasion and proliferation, with small hairpin ribonucleic acid used to knockdown ASPA. Results According to the multivariate Cox regression results, the down-regulated ASPA expression is a distinct prognostic factor. Furthermore, ASPA has significant positive correlations with the infiltration of immune cells in GC lesions. Compared to the non-cancer tissues, the GC tissues had a significantly lower level of ASPA expression (p

Chromium yeast (CY) supplementation has the potential to alleviate the negative effects of heat stress in dairy cows, but the mechanism remains elusive. We aimed to identify the metabolic mechanisms whereby CY supplementation alleviates the negative effects of heat stress in mid-lactation dairy cows. Twelve Holstein dairy cows with similar milk yield (24.6 ± 1.5 kg/d), parity (2 or 3) and days in milk (125 ± 8 d) were fed the same basal diet containing 0.09 mg of Cr/kg DM. They were allocated randomly to 2 groups: a control group (CON, without CY supplementation) and a CY group (CY, administered 0.36 mg Cr/kg DM). The experiment was performed over 8 weeks during a hot summer, in which the mean temperature-humidity index was 79.0 ± 3.13 (>72), indicating that the dairy cows were exposed to heat stress. Chromium yeast supplementation reduced rectal temperature (P = 0.032), and increased the lactation performance by increasing the yield of milk (+2.6 kg/d), protein, lactose and total solid, and protein and lactose percentages in the milk of the heat-stressed dairy cows (P 1.0, P

The microbial genome remains a huge treasure trove for the discovery of diverse natural products. Saccharopolyspora erythraea NRRL23338, the industry producer of erythromycin, has a dozen of biosynthetic gene clusters whose encoding products are unidentified. Heterologous expression of one of the polyketide clusters pks7 in Streptomyces albus B4 chassis resulted in the characterization of its function responsible for synthesizing both 6-methylsalicyclic acid and 6-ethylsalicyclic acid. Meanwhile, two new 6-ethylsalicyclic acid ester derivatives were isolated as shunt metabolites. Their structures were identified by comprehensive analysis of MS and NMR experiments. Putative functions of genes within the pks7 BGC were also discussed.

Soil moisture plays a crucial role in determining the yield of winter wheat. The Huang-Huai-Hai (HHH) Plain is the main growing area of winter wheat in China, and frequent occurrence of drought seriously restricts regional agricultural development. Hence, a daily-scale Non-stationary Standardized Precipitation Evapotranspiration Index (NSPEI), based on winter wheat crop coefficient (Kc), was developed in the present study to evaluate the impact of drought characteristics on winter wheat in different growth stages. Results showed that the water demand for winter wheat decreased with the increase in latitude, and the water shortage was affected by effective precipitation, showing a decreasing trend from the middle to both sides in the HHH Plain. Water demand and water shortage showed an increasing trend at the jointing stage and heading stage, while other growth stages showed a decreasing trend. The spatial distributions of drought duration and intensity were consistent, which were higher in the northern region than in the southern region. Moreover, the water shortage and drought intensity at the jointing stage and heading stage showed an increasing trend. The drought had the greatest impact on winter wheat yield at the tillering stage, jointing stage, and heading stage, and the proportions of drought risk vulnerability in these three stages accounted for 0.25, 0.21, and 0.19, respectively. The high-value areas of winter wheat loss due to drought were mainly distributed in the northeast and south-central regions.

Fruit shape is an important external feature when consumers choose their preferred fruit varieties. Studying persimmon (Diospyros kaki Thunb.) fruit shape is beneficial to increasing its commodity value. However, research on persimmon fruit shape is still in the initial stage. In this study, the mechanism of fruit shape formation was studied by cytological observations, phytohormone assays, and transcriptome analysis using the long fruit and flat fruit produced by ‘Yaoxianwuhua’ hermaphroditic flowers. The results showed that stage 2–3 (June 11–June 25) was the critical period for persimmon fruit shape formation. Persimmon fruit shape is determined by cell number in the transverse direction and cell length in the longitudinal direction. High IAA, GA4, ZT, and BR levels may promote long fruit formation by promoting cell elongation in the longitudinal direction, and high GA3 and ABA levels may be more conducive to flat fruit formation by increasing the cell number in the transverse direction and inhibiting cell elongation in the longitudinal direction, respectively. Thirty-two DEGs related to phytohormone biosynthesis and signaling pathways and nine DEGs related to cell division and cell expansion may be involved in the persimmon fruit shape formation process. These results provide valuable information for regulatory mechanism research on persimmon fruit formation.

This paper investigates a method for precise mapping of human arm movements using sEMG signals. A multi-channel approach captures the sEMG signals, which, combined with the accurately calculated joint angles from an Inertial Measurement Unit, allows for action recognition and mapping through deep learning algorithms. Firstly, signal acquisition and processing were carried out, which involved acquiring data from various movements (hand gestures, single-degree-of-freedom joint movements, and continuous joint actions) and sensor placement. Then, interference signals were filtered out through filters, and the signals were preprocessed using normalization and moving averages to obtain sEMG signals with obvious features. Additionally, this paper constructs a hybrid network model, combining Convolutional Neural Networks and Artificial Neural Networks, and employs a multi-feature fusion algorithm to enhance the accuracy of gesture recognition. Furthermore, a nonlinear fitting between sEMG signals and joint angles was established based on a backpropagation neural network, incorporating momentum term and adaptive learning rate adjustments. Finally, based on the gesture recognition and joint angle prediction model, prosthetic arm control experiments were conducted, achieving highly accurate arm movement prediction and execution. This paper not only validates the potential application of sEMG signals in the precise control of robotic arms but also lays a solid foundation for the development of more intuitive and responsive prostheses and assistive devices.

This examined the effects of Lonicera japonica extract (LJE) with different chlorogenic acid (CGA) contents on lactation performance, antioxidant status and immune function and rumen fermentation in heat-stressed high-yielding dairy cows. In total, 45 healthy Chinese Holstein high-yielding dairy cows, all with similar milk yield, parity, and days in milk were randomly allocated to 3 groups: (1) the control group (CON) without LJE; (2) the LJE-10% CGA group, receiving 35 g/(d·head) of LJE-10% CGA, and (3) the LJE-20% CGA group, receiving 17.5 g/(d·head) of LJE-20% CGA. The results showed that the addition of LJE significantly reduced RT, and enhanced DMI, milk yield, milk composition, and improved rumen fermentation in high-yielding dairy cows experiencing heat stress. Through the analysis of the serum biochemical, antioxidant, and immune indicators, we observed a reduction in CREA levels and increased antioxidant and immune function. In this study, while maintaining consistent CGA content, the effects of addition from both types of LJE are similar. In conclusion, the addition of LJE at a level of 4.1 g CGA/(d·head) effectively relieved heat stress and improved the lactation performance of dairy cows, with CGA serving as the effective ingredient responsible for its anti-heat stress properties.

Nanoparticles (NPs) have been surfacing as a pivotal platform for vaccine development. In our previous work, we developed a cholera toxin B subunit (CTB)-based self-assembled nanoparticle (CNP) and produced highly promising bioconjugate nanovaccines by loading bacterial polysaccharide (OPS) in vivo. In particular, the Klebsiella pneumoniae O2 serotype vaccine showcased a potent immune response and protection against infection. However, extremely low yields limited its further application. In this study, we prepared an efficient Klebsiella pneumoniae bioconjugate nanovaccine in Escherichia coli with a very high yield. By modifying the 33rd glycine (G) in the CNP to aspartate (D), we were able to observe a dramatically increased expression of glycoprotein. Subsequently, through a series of mutations, we determined that G33D was essential to increasing production. In addition, this increase only occurred in engineered E. coli but not in the natural host K. pneumoniae strain 355 (Kp355) expressing OPSKpO2. Next, T-cell epitopes were fused at the end of the CNP(G33D), and animal experiments showed that fusion of the M51 peptide induced high antibody titers, consistent with the levels of the original nanovaccine, CNP-OPSKpO2. Hence, we provide an effective approach for the high-yield production of K. pneumoniae bioconjugate nanovaccines and guidance for uncovering glycosylation mechanisms and refining glycosylation systems.

Nanoparticles (NPs) have been widely utilized in vaccine design. Although numerous NPs have been explored, NPs with adjuvant effects on their own have rarely been reported. We produce a promising self-assembled NP by integrating the pentameric Escherichia coli heat-labile enterotoxin B subunit (LTB) (studied as a vaccine adjuvant) with a trimer-forming peptide. This fusion protein can self-assemble into the NP during expression, and polysaccharide antigens (OPS) are then loaded in vivo using glycosylation. We initially produced two Salmonella paratyphi A conjugate nanovaccines using two LTB subfamilies (LTIB and LTIIbB). After confirming their biosafety in mice, the data showed that both nanovaccines (NP(LTIB)-OPSSPA and NP(LTIIbB)-OPSSPA) elicited strong polysaccharide-specific antibody responses, and NP(LTIB)-OPS resulted in better protection. Furthermore, polysaccharides derived from Shigella or Klebsiella pneumoniae were loaded onto NP(LTIB) and NP(LTIIbB). The animal experimental results indicated that LTIB, as a pentamer module, exhibited excellent protection against lethal infections. This effect was also consistent with that of the reported cholera toxin B subunit (CTB) modular NP in all three models. For the first time, we prepared a novel promising self-assembled NP based on LTIB. In summary, these results indicated that the LTB-based nanocarriers have the potential for broad applications, further expanding the library of self-assembled nanocarriers.

Rice–duckweed coculturing as an advanced technique has proven effective for weed control. However, the complex environmental interactions underlying its effectiveness remain unclear. In this study, a controlled pot experiment was conducted to isolate the shading effect of duckweeds (Landoltia punctata and Spirodela polyrhiza) from their intricate environmental interactions with paddy weeds (Cyperus difformis, Eclipta prostrata, and Ammannia auriculata). The results revealed that as the duckweeds grew, there were notable decreases in total weed density (52.41–77.01%) and biomass (42.33–99.23%) while rice biomass remained unaffected. Duckweed covering allowed less than 8.64% of light to pass through and led to decreases in environmental temperature, pH, and dissolved oxygen concentration in the floodwater, but had little impact on inorganic nitrogen levels. Through screening with random forest analysis and structural equation modelling, it was found that weed density and biomass were predominantly influenced by the reduced light transmittance (54.1% and 77.2%, p ≤ 0.001) resulting from duckweed covering while the decline in dissolved oxygen content partly influenced weed density (18%). In conclusion, this study’s results bring a different perspective, confirming the sunlight-shading effect of duckweed as a critical mechanism significantly inhibiting the germination and growth of weeds. These findings provide a scientific basis for the improved application of ecological weed control methods in paddy fields.

Thermocatalytic decomposition is an efficient purification technology that is potentially applicable to degrading chemical warfare agents and industrial toxic gases. In particular, ZrO2 has attracted attention as a catalyst for the thermocatalytic decomposition of dimethyl methylphosphonate (DMMP), which is a simulant of the nerve gas sarin. However, the influence of the crystal phase and morphology on the catalytic performance of ZrO2 requires further exploration. In this study, monoclinic- and tetragonal-phase ZrO2 (m- and t-ZrO2, respectively) with nanoparticle, flower-like shape and hollow microsphere morphologies were prepared via hydrothermal and solvothermal methods, and their thermocatalytic decomposition of DMMP was systematically investigated. For a given morphology, m-ZrO2 performed better than t-ZrO2. For a given crystalline phase, the morphology of hollow microspheres resulted in the longest protection time. The exhaust gases generated by the thermocatalytic decomposition of DMMP mainly comprised H2, CO2, H2O and CH3OH, and the by-products were phosphorus oxide species. Thus, the deactivation of ZrO2 was attributed to the deposition of these phosphorous oxide species on the catalyst surface. These results are expected to help guide the development of catalysts for the safe disposal of chemical warfare agents.

Abstract Heatwaves impose serious impacts on ecosystems, human health, agriculture, and energy consumption. Previous studies have classified heatwaves into independent daytime, independent nighttime, and compound daytime-nighttime types, and examined the long-term changes in the three types. However, the underlying mechanisms associated with the variations in different heatwave types remain poorly understood. Here we present the first investigation of the local physical processes associated with the daytime, nighttime, and compound heatwaves over the global land during 1979–2020. The results show that three heatwave types occur frequently and increasingly in most regions worldwide. Nighttime and compound heatwaves exhibit stronger increases in both frequency (the yearly number of the events) and fraction (the ratio of the yearly number of one heatwave type to the total yearly number of all types) than daytime heatwaves. Composite diagnostic analyses of local meteorological variables suggest that daytime heatwaves are associated with increased solar radiation under dry conditions and reduced cloud cover and humidity under a clear sky. In contrast, nighttime heatwaves are typically accompanied by moist conditions with increases in cloud fraction, humidity, and longwave radiation at night. These synoptic conditions for daytime and nighttime heatwaves are combined to contribute to compound heatwaves. Local divergences and moisture fluxes responsible for different heatwaves are further revealed. Positive moisture divergence anomalies are seen in most land areas for daytime and compound heatwaves, while they mainly appear in low latitudes for nighttime heatwaves. Our research provides a comprehensive understanding of the local mechanisms of different heatwave types, informing future risks and impact assessments.

Abstract Background Smoking, alcohol consumption, and human papillomavirus (HPV) infection are known risk factors for oral squamous cell carcinoma (OSCC) including SCC of oropharynx (SCCOP) and SCC of oral cavity (SCCOC). Researchers have examined each of these risk factors independently, but few have observed the potential risk of their interaction. This study investigated the interactions among these risk factors and risk of OSCC. Methods Totally 377 patients with newly diagnosed SCCOP and SCCOC and 433 frequency-matched cancer-free controls by age and sex were included. Multivariable logistic regression was performed to calculate ORs and 95% CIs. Results We found that overall OSCC risk was independently associated with smoking (adjusted OR(aOR), 1.4; 95%CI, 1.0–2.0), alcohol consumption (aOR, 1.6; 95%CI, 1.1–2.2), and HPV16 seropositivity (aOR, 3.3; 95%CI, 2.2–4.9), respectively. Additionally, we found that HPV16 seropositivity increased the risk of overall OSCC in ever-smokers (aOR, 6.8; 95%CI, 3.4–13.4) and ever-drinkers (aOR, 4.8; 95%CI, 2.9–8.0), while HPV16-seronegative ever-smokers and ever-drinkers had less than a twofold increase in risk of overall OSCC (aORs, 1.2; 95%CI, 0.8–1.7 and 1.8; 95%CI, 1.2–2.7, respectively). Furthermore, the increased risk was particularly high for SCCOP in HPV16-seropositive ever-smokers (aOR, 13.0; 95%CI, 6.0–27.7) and in HPV16-seropositive ever-drinkers (aOR, 10.8; 95%CI, 5.8–20.1), while the similar increased risk was not found in SCCOC. Conclusion These results suggest a strong combined effect of HPV16 exposure, smoking, and alcohol on overall OSCC, which may indicate a strong interaction between HPV16 infection and smoking and alcohol consumption, particularly for SCCOP.

Abstract Artificially improving persimmon (Diospyros kaki Thunb.), one of the most important fruit trees, remains challenging owing to the lack of reference genomes. In this study, we generated an allele-aware chromosome-level genome assembly for the autohexaploid persimmon ‘Xiaoguotianshi’ (Chinese-PCNA type) using PacBio CCS and Hi-C technology. The final assembly contained 4.52 Gb, with a contig N50 value of 5.28 Mb and scaffold N50 value of 44.01 Mb, of which 4.06 Gb (89.87%) of the assembly were anchored onto 90 chromosome-level pseudomolecules comprising 15 homologous groups with 6 allelic chromosomes in each. A total of 153,288 protein-coding genes were predicted, of which 98.60% were functionally annotated. Repetitive sequences accounted for 64.02% of the genome; and 110,480 rRNAs, 12,297 tRNAs, 1,483 miRNAs, and 3,510 snRNA genes were also identified. This genome assembly fills the knowledge gap in the autohexaploid persimmon genome, which is conducive in the study on the regulatory mechanisms underlying the major economically advantageous traits of persimmons and promoting breeding programs.

Abstract Background Kidney tumors have become increasingly prevalent among adults and are now considered one of the most common types of tumors. Accurate segmentation of kidney tumors can help physicians assess tumor complexity and aggressiveness before surgery. However, segmenting kidney tumors manually can be difficult because of their heterogeneity. Methods This paper proposes a 2.5D MFFAU-Net (multi-level Feature Fusion Attention U-Net) to segment kidneys, tumors and cysts. First, we propose a 2.5D model for learning to combine and represent a given slice in 2D slices, thereby introducing 3D information to balance memory consumption and model complexity. Then, we propose a ResConv architecture in MFFAU-Net and use the high-level and low-level feature in the model. Finally, we use multi-level information to analyze the spatial features between slices to segment kidneys and tumors. Results The 2.5D MFFAU-Net was evaluated on KiTS19 and KiTS21 kidney datasets and demonstrated an average dice score of 0.924 and 0.875, respectively, and an average Surface dice (SD) score of 0.794 in KiTS21. Conclusion The 2.5D MFFAU-Net model can effectively segment kidney tumors, and the results are comparable to those obtained with high-performance 3D CNN models, and have the potential to serve as a point of reference in clinical practice.

Abstract Background Brucellosis is a chronic zoonotic disease, and Ningxia is one of the high prevalence regions in China. To mitigate the spread of brucellosis, the government of Ningxia has implemented a comprehensive prevention and control plan (2022-2024). It is meaningful to quantitatively evaluate the accessibility of this strategy. Methods Based on the transmission characteristics of brucellosis in Ningxia, we propose a dynamical model of sheep-human-environment, which coupling with the stage structure of sheep and indirect environmental transmission. We first calculate the basic reproduction number $$R_0$$ R 0 and use the model to fit the data of human brucellosis. Then, three widely applied control strategies of brucellosis in Ningxia, that is, slaughtering of sicked sheep, health education to high risk practitioners, and immunization of adult sheep, are evaluated. Results The basic reproduction number is calculated as $$R_{0}=1.47$$ R 0 = 1.47 , indicating that human brucellosis will persist. The model has a good alignment with the human brucellosis data. The quantitative accessibility evaluation results show that current brucellosis control strategy may not reach the goal on time. “Ningxia Brucellosis Prevention and Control Special Three-Year Action Implementation Plan (2022-2024)” will be achieved in 2024 when increasing slaughtering rate $$\gamma$$ γ by 30 $$\%$$ % , increasing health education to reduce $$\beta _{h}$$ β h to 50 $$\%$$ % , and an increase of immunization rate of adult sheep $$\theta$$ θ by 40 $$\%$$ % . Conclusion The results demonstrate that the comprehensive control measures are the most effective for brucellosis control, and it is necessary to further strengthen the multi-sectoral joint mechanism and adopt integrated measures to prevention and control brucellosis. These results can provide a reliable quantitative basis for further optimizing the prevention and control strategy of brucellosis in Ningxia.

Abstract Background Engineered strains of Escherichia coli have been used to produce bioconjugate vaccines using Protein Glycan Coupling Technology (PGCT). Nanovaccines have also entered the vaccine development arena with advances in nanotechnology and have been significantly developed, but chassis cells for conjugate nanovaccines have not been reported. Results To facilitate nanovaccine preparation, a generic recombinant protein (SpyCather4573) was used as the acceptor protein for O-linked glycosyltransferase PglL, and a glycol-engineered Escherichia coli strain with these two key components (SC4573 and PglL) integrated in its genome was developed in this study. The targeted glycoproteins with antigenic polysaccharides produced by our bacterial chassis can be spontaneously bound to proteinous nanocarriers with surface exposed SpyTag in vitro to form conjugate nanovaccines. To improve the yields of the targeted glycoprotein, a series of gene cluster deletion experiments was carried out, and the results showed that the deletion of the yfdGHI gene cluster increased the expression of glycoproteins. Using the updated system, to the best of our knowledge, we report for the first time the successful preparation of an effective Klebsiella pneumoniae O1 conjugate nanovaccine (KPO1-VLP), with antibody titers between 4 and 5 (Log10) after triple immunization and up to 100% protection against virulent strain challenge. Conclusions Our results define a convenient and reliable framework for bacterial glycoprotein vaccine preparation that is flexible and versatile, and the genomic stability of the engineered chassis cells promises a wide range of applications for biosynthetic glycobiology research.

Abstract Background Lentinan (LNT) is a complex fungal component that possesses effective antitumor and immunostimulating properties. However, there is a paucity of studies regarding the effects and mechanisms of LNT on type 1 diabetes. Objective In the current study, we investigated whether an intraperitoneal injection of LNT can diminish the risk of developing type 1 diabetes (T1D) in non-obese diabetic (NOD) mice and further examined possible mechanisms of LNT’s effects. Methods: Pre-diabetic female NOD mice 8 weeks of age, NOD mice with 140–160 mg/dL, 200–230 mg/dL or 350–450 mg/dL blood glucose levels were randomly divided into two groups and intraperitoneally injected with 5 mg/kg LNT or PBS every other day. Then, blood sugar levels, pancreas slices, spleen, PnLN and pancreas cells from treatment mice were examined. Results Our results demonstrated that low-dosage injections (5 mg/kg) of LNT significantly suppressed immunopathology in mice with autoimmune diabetes but increased the Foxp3+ regulatory T cells (Treg cells) proportion in mice. LNT treatment induced the production of Tregs in the spleen and PnLN cells of NOD mice in vitro. Furthermore, the adoptive transfer of Treg cells extracted from LNT-treated NOD mice confirmed that LNT induced Treg function in vivo and revealed an enhanced suppressive capacity as compared to the Tregs isolated from the control group. Conclusion LNT was capable of stimulating the production of Treg cells from naive CD4 + T cells, which implies that LNT exhibits therapeutic values as a tolerogenic adjuvant and may be used to reverse hyperglycaemia in the early and late stages of T1D.

In this work, the authors demonstrate that LLPS of the quaternary USH2 protein complex initiates the formation of stereociliary ankle link condensates, providing insights into the pathogenesis of deafness.

Abstract Background Bone is one of the most frequent sites for breast cancer metastasis. Breast cancer bone metastasis (BCBM) leads to skeletal morbidities including pain, fractures, and spinal compression, all of which severely impact quality of life. Immunotherapy is a promising therapy for patients with advanced cancer, but whether it may provide benefit to metastatic bone cancer is currently unknown. Thus, a better understanding of the immune landscape of bone-disseminated breast cancers may reveal new therapeutic strategies. In this study, we use histopathological analysis to investigate changes within the immune microenvironment of primary breast cancer and paired BCBM. Methods Sixty-three patients with BCBM, including 31 with paired primary and bone metastatic lesions, were included in our study. The percentage of stroma and stromal tumor-infiltrating lymphocytes (TILs) was evaluated by histopathological analysis. The quantification of stromal TILs (CD4 + and CD8 +), macrophages (CD68 + and HLA-DR +), programmed cell death protein 1 (PD-1), and programmed cell death protein ligand 1 (PD-L1) was evaluated through immunohistochemical (IHC) staining. Statistical analysis was performed with paired t test, Wilcoxon test, spearman correlation test, and univariate and multivariate cox regression. Results Median survival after BCBM pathological diagnosis was 20.5 months (range: 3–95 months). Of the immune parameters measured, none correlated with survival after bone metastasis was diagnosed. Compared to the primary site, bone metastases exhibited more tumor stroma (mean: 58.5% vs 28.87%, p

Increasing the osteogenic differentiation ability and decreasing the adipogenic differentiation ability of bone marrow mesenchymal stem cells (BMSCs) is a potential strategy for the treatment of osteoporosis (OP). Naturally derived oligosaccharides have shown significant anti-osteoporotic effects. Nystose (NST), an oligosaccharide, was isolated from the roots of Morinda officinalis How. (MO). The aim of the present study was to investigate the effects of NST on bone loss in ovariectomized mice, and explore the underlying mechanism of NST in promoting differentiation of BMSCs to osteoblasts. Administration of NST (40, 80 and 160 mg/kg) and the positive control of estradiol valerate (0.2 mg/kg) for 8 weeks significantly prevented bone loss induced by ovariectomy (OVX), increased the bone mass density (BMD), improved the bone microarchitecture and reduced urine calcium and deoxypyridinoline (DPD) in ovariectomized mice, while inhibited the increase of body weight without significantly affecting the uterus weight. Furthermore, we found that NST increased osteogenic differentiation, inhibited adipogenic differentiation of BMSCs in vitro, and upregulated the expression of the key proteins of BMP and Wnt/β-catenin pathways. In addition, Noggin and Dickkopf-related protein-1 (DKK-1) reversed the effect of NST on osteogenic differentiation and expression of the key proteins in BMP and Wnt/β-catenin pathway. The luciferase activities and the molecular docking analysis further supported the mechanism of NST. In conclusion, these results indicating that NST can be clinically used as a potential alternative medicine for the prevention and treatment of postmenopausal osteoporosis.

Cancer metabolism has emerged as a pivotal area of research recently. The ability to visualize and comprehend the metabolic processes of cancer holds immense clinical value, particularly in the diagnosis of malignant tumors and the assessment of treatment responses. Deuterium Metabolic Imaging (DMI), as a robust, simple, and versatile MR spectroscopic imaging tool, demonstrates promise in tumor diagnosis and treatment efficacy assessment. This review explored the latest developments and applications of DMI in oncology across various tumor metabolic axes, with a specific emphasis on its potential for clinical translation. DMI offers invaluable insights into tumor biology, treatment responses, and prognostic outcomes. Notably, DMI can identify early responses to immunotherapy, a prominent area of current research interest. In conclusion, DMI harbors the potential to evolve into a convenient and efficient imaging technique in clinical practice, thereby advancing precision medicine and improving the diagnosis and evaluation of cancer treatments.

Abstract The rigid body localization (RBL) technique is capable of estimating the state of a rigid body, including its translation and orientation, by utilizing the interactions between sensors and landmarks. The prevalent RBL methods employ precise time‐of‐flight measurements (or range measurements) to estimate the state. However, the clock offsets in range measurements in asynchronous networks are unavoidable, leading to performance degradation for state estimators. Therefore, range difference measurements have been adopted to solve the RBL problem. However, existing approaches struggle to achieve desirable performance while maintaining computational efficiency. To address this issue, a new closed‐form state estimator for asynchronous networks is introduced. The proposed algorithm leverages the Taylor‐series expansion technique to enhance accuracy while keeping computational overhead low. Numerical experiments demonstrate that the proposed method achieves state‐of‐the‐art performance with high computational efficiency under small Gaussian noises.

IntroductionBreast cancer (BC) is now the most common type of cancer in women. Disulfidptosis is a new regulation of cell death (RCD). RCD dysregulation is causally linked to cancer. However, the comprehensive relationship between disulfidptosis and BC remains unknown. This study aimed to explore the predictive value of disulfidptosis-related genes (DRGs) in BC and their relationship with the TME.MethodsThis study obtained 11 disulfidptosis genes (DGs) from previous research by Gan et al. RNA sequencing data of BC were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO) databases. First, we examined the effect of DG gene mutations and copy number changes on the overall survival of breast cancer samples. We then used the expression profile data of 11 DGs and survival data for consensus clustering, and BC patients were divided into two clusters. Survival analysis, gene set variation analysis (GSVA) and ss GSEA were used to compare the differences between them. Subsequently, DRGs were identified between the clusters used to perform Cox regression and least absolute shrinkage and selection operator regression (LASSO) analyses to construct a prognosis model. Finally, the immune cell infiltration pattern, immunotherapy response, and drug sensitivity of the two subtypes were analyzed. CCK-8 and a colony assay obtained by knocking down genes and gene sequencing were used to validate the model.ResultTwo DG clusters were identified based on the expression of 11DGs. Then, 225 DRGs were identified between them. RS, composed of six genes, showed a significant relationship with survival, immune cell infiltration, clinical characteristics, immune checkpoints, immunotherapy response, and drug sensitivity. Low-RS shows a better prognosis and higher immunotherapy response than high-RS. A nomogram with perfect stability constructed using signature and clinical characteristics can predict the survival of each patient. CCK-8 and colony assay obtained by knocking down genes have demonstrated that the knockdown of high-risk genes in the RS model significantly inhibited cell proliferation.DiscussionThis study elucidates the potential relationship between disulfidptosis-related genes and breast cancer and provides new guidance for treating breast cancer.

Ciliated sensory cells such as photo- and olfactory receptors employ multiple types of opsins or hundreds of unique olfactory G-protein coupled receptors to respond to various wavelengths of light or odorants. With respect to hearing and balance, the mechanotransduction machinery involves fewer variants; however, emerging evidence suggests that specialization occurs at the molecular level. To address how the mechanotransduction complex varies in the inner ear, we characterized the expression of paralogous genes that encode components required for mechanotransduction in zebrafish hair cells using RNA-FISH and bioinformatic analysis. Our data indicate striking zonal differences in the expression of two components of the mechanotransduction complex which are known to physically interact, the transmembrane channel-like 1 and 2 (tmc1/2) family members and the calcium and integrin binding 2 and 3 (cib2/3) paralogues. tmc1, tmc2b, and cib3 are largely expressed in peripheral or extrastriolar hair cells, whereas tmc2a and cib2 are enriched in central or striolar hair cells. In addition, a gene implicated in deaf-blindness, ush1c, is highly enriched in a subset of extrastriolar hair cells. These results indicate that specific combinations of these components may optimize responses to mechanical stimuli in subtypes of sensory receptors within the inner ear.