Metabolomics analysis of different diameter classes of Taxus chinensis reveals that the resource allocation is related to carbon and nitrogen metabolism.

Taxus chinensis (Taxus cuspidata Sieb. et Zucc.) is a traditional medicinal plant known for its anticancer substance paclitaxel, and its growth age is also an important factor affecting its medicinal value. However, how age affects the physiological and metabolic characteristics and active substances of T. chinensis is still unclear. In this study, carbon and nitrogen accumulation, contents of active substances and changes in primary metabolites in barks and annual leaves of T. chinensis of different diameter classes were investigated by using diameter classes instead of age. The results showed that leaves and barks of small diameter class (D1) had higher content of non-structural carbohydrates and C, which were effective in enhancing defense capacity, while N content was higher in medium (D2) and large diameter classes (D3). Active substances such as paclitaxel, baccatin III and cephalomannine also accumulated significantly in barks of large diameter classes. Moreover, 21 and 25 differential metabolites were identified in leaves and barks of different diameter classes, respectively. The differential metabolites were enhanced the TCA cycle and amino acid biosynthesis, accumulate metabolites such as organic acids, and promote the synthesis and accumulation of active substances such as paclitaxel in the medium and large diameter classes. These results revealed the carbon and nitrogen allocation mechanism of different diameter classes of T. chinensis, and its relationship with medicinal components, providing a guidance for the harvesting and utilization of wild T. chinensis.

Preparation and drug release performance of different gelation type polysaccharide/ß-lactoglobulin fiber composite gels.

Self-assembled protein fibers have attracted much attention in the fields of medicine and food because of their high aspect ratio, polymorphic structure and strong surface hydrophobicity. In this study, three different gelation types of polysaccharides/ß-lactoglobulin fiber (Fblg) composite gels, including ionic alginate-Fblg gels, synergistic xanthan-Fblg gels, and double network agar-Fblg gels, were first prepared. The interactions between the polysaccharides and the Fblgs, the microstructure and mechanical properties of the composite gels were investigated using the light scattering, scanning electron microscopy, rheology and texture analysis in order to reveal their formation mechanisms. Then the loading and release properties of the water-soluble drug 5-fluorouracil (5-FU) and the hydrophobic drug curcumin (Cur) through these composite gels were further studied with release mechanisms determined by fitting different release models. It was found that the mechanical properties of the composite gels were determined by the mesh density of the three-dimensional networks formed inside the gels. The network structure and mechanical strength of the alginate-Fblg gels became weaker with the increase of Fblg content at pH 4 due to their attractive interaction which hindered the binding of Ca2+ to ALG, while the network and the strength of the alginate-Fblg gels didn't change much at pH 7 due to the repulsion between Alg and Fblg. The xanthan-Fblg gels formed lamellar structures with enhanced gel network and mechanical strength due to the hydrogen bonding and the electrostatic interaction with Fblg. The Agar-Fblg composite gel formed at 60 °C (above the gelation temperature of agar of 40 °C) had a denser double network structure and higher mechanical strength than that formed at 0 °C due to inhibition of diffusion of Ca2+ as salt bridges for Fblg. The hydrophilic drugs were loaded in the meshes of the composite gels and their release was determined by the structure of the composite gel networks, whereas the hydrophobic drugs were loaded by attaching to the Fblgs in the composite gels and their release was determined by the loading ability and strength of the gels. The study not only provided a new idea for the preparation and application of polysaccharide-protein fiber composite hydrogels, but also provided insights for improving the efficiency of drug carriers.

Case report: Experience and insights on the treatment of two cases of cryptococcal meningitis during the later stages of the COVID-19 pandemic.

In the late stages of the COVID-19 pandemic, there's an increasing trend in opportunistic infections, including bacterial and fungal infections. This study discusses the treatment process of two cases of cryptococcal meningitis during the COVID-19 pandemic. It highlights the importance of laboratory testing for these co-infections and stresses the need for vigilance, early diagnosis, and proactive treatment to improve patient outcomes in the post-pandemic era.

Evaluation of volatile components from the tuber, fibrous roots, bud, stem and leaf tissues of Bletilla striata for its anti-colon cancer activity.

Bletilla striata (Thunb.) Rchb.f., a medicinal plant in the Orchidaceae family, is mainly found in East Asia and has extensive pharmacological activities. Plant's volatile components are important active ingredients with a wide range of physiological activities, and B. striata has a special odor and unique volatile components. Yet it has received little attention, hindering a full understanding of its phytochemical components. Employing the ultrasonic-assisted extraction method, the volatile components of B. striata's fibrous root, bud, aerial part and tuber were extracted, resulting in yields of 0.06%, 0.64%, 3.38% and 4.47%, respectively. A total of 78 compounds were identified from their chemical profiles using gas chromatography-mass spectrometry (GC-MS), including 45 components with the main compounds of linoleic acid (content accounting for 31.23%), n-hexadecanoic acid (13.53%), and octadecanoic acid (9.5%) from the tuber, 34 components with the main compounds of eicosane, 2-methyl- (28.42%), linoelaidic acid (10.43%), linoleic acid (4.53%), and n-hexadecanoic acid (6.91%) from the fibrous root, 38 components with the main compounds of pentadeca-6,9-dien-1-ol (9.29%), n-hexadecanoic acid (11%), eicosane,2-methyl- (23.43%), and linoleic acid (23.53%) from the bud, and 27 components with the main compounds of linoelaidic acid (5.97%), n-hexadecanoic acid (15.99%), and linolenic acid ethyl ester (18.9%) from the aerial part. Additionally, the growth inhibition activity against colon cancer HCT116 cells was evaluated using sulforhodamine B (SRB) assay and the thiazolyl blue tetrazolium bromide (MTT) assay, and the accumulation of reactive oxygen species (ROS) was determined using dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining and fluorescence intensity analysis. The volatile extracts exhibited significant growth inhibitory efficacy against HCT116 cells, with half-maximal inhibitory concentration (IC50) values of 3.65, 2.32, 2.42 and 3.89 mg/mL in the SRB assay, and 3.55, 2.58, 3.12 and 4.80 mg/mL in the MTT assay for the root, bud, aerial part, and tuber, respectively. Notably, treatment with the aerial part extract caused morphological changes in the cells and significantly raised the intracellular ROS level. In summary, the chemical profiles of the volatile components of B. striata were revealed for the first time, demonstrating a certain tissue specificity. Additionally, it demonstrated for the first time that these volatile extracts possess potent anti-colon cancer activity, highlighting the importance of these volatile components in B. striata's medicinal properties.

Revealing the impact of thermal annealing on the perovskite/organic bulk heterojunction interface in photovoltaic devices.

Perovskite/organic bulk heterojunction (BHJ) integrated solar cells have tremendous development potential to exceed the Shockley-Queisser limit efficiency of single-junction photovoltaics, due to the merits of spectra response extension. However, the presence of energy level barriers and severe non-radiative recombination at the interface between perovskite and BHJ greatly hindered the transport and collection of charge carriers, usually leading to large Voc and photocurrent loss, as well as the stability degradation of integrated devices. Therefore, investigating the interface properties of perovskite/BHJ is crucial for understanding the charge transport process and enhancing device performance. In this study, we effectively regulated the interface properties and charge transport in perovskite/BHJ integrated devices using a thermal annealing process. Using Kelvin probe microscopy, photoluminescence, and transient absorption spectroscopy, we revealed that moderate annealing treatment would contribute to forming close interface contact and provide more channels or pathways for charge transfer, which is advantageous for the interface charge collection and device performance. In addition, the lone pair electrons of acyl, thiophene and pyrrole function groups in polymer PDPP3T and PCBM can act as the Lewis base and provide electrons to the under-coordinated lead atoms or clusters in the perovskite, effectively passivating traps on the surface and grain boundaries of the perovskite through Lewis acid-base coordination. Finally, we improved the photovoltaic conversion efficiency of the device to 21.57% with enhanced stability using an optimized thermal annealing process. This study provides a comprehensive understanding of the integrated perovskite/BHJ interface properties, which could be extended to other optoelectronic devices based on a similar integrated structure.

In Vitro Modeling of Recurrent Dermatofibrosarcoma Protuberans: Assessment of 5-Aminolevulinic Acid Photodynamic Therapy Efficacy.

BACKGROUND: Dermatofibrosarcoma Protuberans (DFSP) is a rare, low-grade malignant tumor of the dermis with a high recurrence rate post-surgery. Current treatments, including surgery, radiotherapy, and targeted therapy, have limitations. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) is a promising non-invasive approach, but its efficacy in DFSP treatment remains underexplored. METHODS: This study aimed to evaluate the anti-tumor efficacy of 5-ALA PDT using an in vitro model derived from a recurrent DFSP patient. The cells were treated with varying concentrations of 5-ALA and exposed to red light, followed by assessments of cell viability, proliferation, apoptosis, migration, invasion, angiogenesis, and expression of DFSP-related genes and proteins. RESULTS: 5-ALA PDT significantly reduced DFSP cell viability in a dose-dependent manner and induced apoptosis. It also effectively inhibited cell proliferation, migration, and invasion, as well as suppressed angiogenic activity in conditioned media. Furthermore, 5-ALA PDT downregulated the expression of COL1A1 and PDGFRB, key genes in DFSP pathogenesis. CONCLUSIONS: The findings provide the first evidence of 5-ALA PDT's in vitro anti-tumor efficacy against DFSP, suggesting its potential as a novel therapeutic approach for DFSP. Further studies are warranted to explore the clinical utility of 5-ALA PDT in preventing DFSP recurrence.

Interspecies interactions in dairy biofilms drive community structure and response against cleaning and disinfection.

Interspecies interactions within a biofilm community influence population dynamics and community structure, which in turn may affect the bacterial stress response to antimicrobials. This study was conducted to assess the impact of interactions between Kocuria salsicia and a three-species biofilm community (comprising Stenotrophomonas rhizophila, Bacillus licheniformis, and Microbacterium lacticum) on biofilm mass, the abundance of individual species, and their survival under a laboratory-scale cleaning and disinfection (C&D) regime. The presence of K. salsicia enhanced the cell numbers of all three species in pairwise interactions. The outcomes derived from summing up pairwise interactions did not accurately predict the bacterial population dynamics within communities of more than two species. In four-species biofilms, we observed the dominance of S. rhizophila and B. licheniformis, alongside a concurrent reduction in the cell counts of K. salsicia and M. lacticum. This pattern suggests that the underlying interactions are not purely non-transitive; instead, a more complex interplay results in the dominance of specific species. We observed that bacterial spatial organization and matrix production in different mixed-species combinations affected survival in response to C&D. Confocal microscopy analysis of spatial organization showed that S. rhizophila localized on the biofilm formed by B. licheniformis and M. lacticum, and S. rhizophila was more susceptible to C&D. Matrix production in B. licheniformis, evidenced by alterations in biofilm mass and by scanning electron microscopy, demonstrated its protective role against C&D, not only for this species itself, but also for neighbouring species. Our findings emphasise that various social interactions within a biofilm community not only affect bacterial population dynamics but also influence the biofilm community's response to C&D stress.

Phosphorylation-Driven Epichaperome Assembly: A Critical Regulator of Cellular Adaptability and Proliferation.

The intricate protein-chaperone network is vital for cellular function. Recent discoveries have unveiled the existence of specialized chaperone complexes called epichaperomes, protein assemblies orchestrating the reconfiguration of protein-protein interaction networks, enhancing cellular adaptability and proliferation. This study delves into the structural and regulatory aspects of epichaperomes, with a particular emphasis on the significance of post-translational modifications in shaping their formation and function. A central finding of this investigation is the identification of specific PTMs on HSP90, particularly at residues Ser226 and Ser255 situated within an intrinsically disordered region, as critical determinants in epichaperome assembly. Our data demonstrate that the phosphorylation of these serine residues enhances HSP90's interaction with other chaperones and co-chaperones, creating a microenvironment conducive to epichaperome formation. Furthermore, this study establishes a direct link between epichaperome function and cellular physiology, especially in contexts where robust proliferation and adaptive behavior are essential, such as cancer and stem cell maintenance. These findings not only provide mechanistic insights but also hold promise for the development of novel therapeutic strategies targeting chaperone complexes in diseases characterized by epichaperome dysregulation, bridging the gap between fundamental research and precision medicine.

Integrated proteomics reveals autophagy landscape and an autophagy receptor controlling PKA-RI complex homeostasis in neurons.

Autophagy is a conserved, catabolic process essential for maintaining cellular homeostasis. Malfunctional autophagy contributes to neurodevelopmental and neurodegenerative diseases. However, the exact role and targets of autophagy in human neurons remain elusive. Here we report a systematic investigation of neuronal autophagy targets through integrated proteomics. Deep proteomic profiling of multiple autophagy-deficient lines of human induced neurons, mouse brains, and brain LC3-interactome reveals roles of neuronal autophagy in targeting proteins of multiple cellular organelles/pathways, including endoplasmic reticulum (ER), mitochondria, endosome, Golgi apparatus, synaptic vesicle (SV) for degradation. By combining phosphoproteomics and functional analysis in human and mouse neurons, we uncovered a function of neuronal autophagy in controlling cAMP-PKA and c-FOS-mediated neuronal activity through selective degradation of the protein kinase A - cAMP-binding regulatory (R)-subunit I (PKA-RI) complex. Lack of AKAP11 causes accumulation of the PKA-RI complex in the soma and neurites, demonstrating a constant clearance of PKA-RI complex through AKAP11-mediated degradation in neurons. Our study thus reveals the landscape of autophagy degradation in human neurons and identifies a physiological function of autophagy in controlling homeostasis of PKA-RI complex and specific PKA activity in neurons.

The Efficacy & Molecular Mechanisms of a Terpenoid Compound Ganoderic Acid C1 on Corticosteroid-Resistant Neutrophilic Airway Inflammation: In vivo and in vitro Validation.

Introduction: Neutrophil predominant airway inflammation is associated with severe and steroid-resistant asthma clusters. Previously, we reported efficacy of ASHMI, a three-herb TCM asthma formula in a steroid-resistant neutrophil-dominant murine asthma model and further identified Ganoderic Acid C1 (GAC1) as a key ASHMI active compound in vitro. The objective of this study is to investigate GAC1 effect on neutrophil-dominant, steroid-resistant asthma in a murine model. Methods: In this study, Balb/c mice were systematically sensitized with ragweed (RW) and alum and intranasally challenged with ragweed. Unsensitized/PBS challenged mice served as normal controls. Post sensitization, mice were given 4 weeks of oral treatment with GAC1 or acute dexamethasone (Dex) treatment at 48 hours prior to challenge. Pulmonary cytokines were measured by ELISA, and lung sections were processed for histology by H&E staining. Furthermore, GAC1 effect on MUC5AC expression and on reactive oxygen species (ROS) production in human lung epithelial cell line (NCI-H292) was determined by qRT-PCR and ROS assay kit, respectively. Computational analysis was applied to select potential targets of GAC1 in steroid-resistant neutrophil-dominant asthma. Molecular docking was performed to predict binding modes between GAC1 and Dex with TNF-α. Results: The result of the study showed that chronic GAC1 treatment, significantly reduced pulmonary inflammation (P < 0.01-0.001 vs Sham) and airway neutrophilia (P < 0.01 vs Sham), inhibited TNF-α, IL-4 and IL-5 levels (P < 0.05-0.001 vs Sham). Acute Dex treatment reduced eosinophilic inflammation and IL-4, IL-5 levels, but had no effect on neutrophilia and TNF-α production. GAC1 treated H292 cells showed decreased MUC5AC gene expression and production of ROS (P < 0.001 vs stimulated/untreated cells). Molecular docking results showed binding energy of complex GAC1-TNF was -10.8 kcal/mol. Discussion: GAC1 may be a promising anti-asthma botanical drug for treatment of steroid-resistant asthma.

Remodeling the Homologous Recombination Mechanism of Yarrowia lipolytica for High-Level Biosynthesis of Squalene.

Squalene is a high-value antioxidant with many commercial applications. The use of microbial cell factories to produce squalene as an alternative to plant and animal extracts could meet increasing market demand. Yarrowia lipolytica is an excellent host for squalene production due to its high levels of acetyl-CoA and a hydrophobic environment. However, the need for precise and complicated gene editing has hindered the industrialization of this strain. Herein, the rapid construction of a strain with high squalene production was achieved by enhancing the homologous recombination efficiency in Y. lipolytica. First, remodeling of the homologous recombination efficiency resulted in a 10-fold increase in the homologous recombination rate. Next, the whole mevalonate pathway was integrated into the chromosome to enhance squalene production. Then, a higher level of squalene accumulation was achieved by increasing the level of acetyl coenzyme A and regulating the downstream steroid synthesis pathway. Finally, the squalene production reached 35 g/L after optimizing the fermentation conditions and performing a fed-batch culture in a 5 L jar fermenter. This is the highest squalene production ever reported to date by de novo biosynthesis without adding any inhibitors, paving a new path toward the industrial production of squalene and its downstream products.

A comparative study of the use of digital technology in the anterior smile experience.

OBJECTIVES: this study aims to compare the clinical outcomes of traditional and digital crown extension guides in the aesthetic restoration of anterior teeth. Additionally, the study will analyze the differences in the results of various digital crown extension guides in anterior aesthetic restorations. METHODS: Sixty-two patients who required aesthetic restoration of their anterior teeth were selected for this study. The patients had a total of 230 anterior teeth and were randomly divided into three groups: a control group of 22 cases who received diagnostic wax-up with pressure film, an experimental group 1 of 20 cases who received 3D printed digital models with pressure film, and an experimental group 2 of 20 patients who received digital dual-positioning guides. The control group had a total of 84 anterior teeth, experimental group 1 had 72 anterior teeth, and experimental group 2 had 74 anterior teeth. The study compared three methods for fabricating crown extension guides: the control group used the diagnostic wax-up plus compression film method, while experimental group 1 used compression film on 3D printed models and experimental group 2 used 3D printed digital dual-positioning crown extension guides. After the crown lengthening surgery, the control group patients wore DMG resin temporary crown material for gingival contouring, while the experimental group patients wore 3D printed resin temporary crowns for the same purpose. The patients were followed up in the outpatient clinic after wearing temporary crowns for 1 month, 3 months, and 6 months, respectively. The clinical results were evaluated in terms of marginal fit, red aesthetic index, and white aesthetic index. RESULTS: Based on the statistical analysis, the experimental group required significantly fewer follow-up visits and less time for guide design and fabrication compared to the control group. Additionally, the surgical time for the experimental group was significantly shorter than that of the control group. During the postoperative period between the 1st and 3rd month, the PES index scores for the marginal gingival level, proximal, and distal mesiodistal gingival papillae of the experimental group showed a trend of superiority over those of the control group. By the 6th month, the marginal gingival level exhibited a significant difference between the experimental and control groups. The experimental group demonstrated superior results to the control group in terms of shape, contour, and volume of the teeth, color, surface texture, and transparency of the restorations, and features during the 1st and 3rd postoperative months. In the 6th month, the comparative results indicated that the experimental group continued to exhibit superior outcomes to the control group in terms of the shape, color, surface texture, and transparency of the restorations, as well as the characteristics of the teeth. Additionally, the experimental group demonstrated significantly fewer gingival alterations than the control group at 1 month, 3 months, and 6 months post-procedure, with this difference being statistically significant. Furthermore, the combination of 3D printing technology and restorative techniques was utilized, resulting in consistent patient satisfaction. CONCLUSION: Digitalisation plays an important role in anterior aesthetic restorations. The use of digital technology to manage the entire process of anterior cosmetic restorations can improve restorative results, reduce the number of follow-up appointments, shorten consultation time, and achieve better patient satisfaction.

Ultra-processed foods and human health: An umbrella review and updated meta-analyses of observational evidence.

BACKGROUND & AIMS: Ultra-processed food (UPF) intake has increased sharply over the last few decades and has been consistently asserted to be implicated in the development of non-communicable diseases. We aimed to evaluate and update the existing observational evidence for associations between ultra-processed food (UPF) consumption and human health. METHODS: We searched Medline and Embase from inception to March 2023 to identify and update meta-analyses of observational studies examining the associations between UPF consumption, as defined by the NOVA classification, and a wide spectrum of health outcomes. For each health outcome, we estimated the summary effect size, 95% confidence interval (CI), between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. These metrics were used to evaluate evidence credibility of the identified associations. RESULTS: This umbrella review identified 39 meta-analyses on the associations between UPF consumption and health outcomes. We updated all meta-analyses by including 122 individual articles on 49 unique health outcomes. The majority of the included studies divided UPF consumption into quartiles, with the lowest quartile being the reference group. We identified 25 health outcomes associated with UPF consumption. For observational studies, 2 health outcomes, including renal function decline (OR: 1.25; 95% CI: 1.18, 1.33) and wheezing in children and adolescents (OR: 1.42; 95% CI: 1.34, 1.49), showed convincing evidence (Class I); and five outcomes were reported with highly suggestive evidence (Class II), including diabetes mellitus, overweight, obesity, depression, and common mental disorders. CONCLUSIONS: High UPF consumption is associated with an increased risk of a variety of chronic diseases and mental health disorders. At present, not a single study reported an association between UPF intake and a beneficial health outcome. These findings suggest that dietary patterns with low consumption of UPFs may render broad public health benefits.

Insect root feeders incur negative density-dependent damage across plant species in an alpine meadow.

Although herbivores are well known to incur positive density-dependent damage and mortality, thereby likely shaping plant community assembly, the response of belowground root feeders to changes in plant density has seldom been addressed. Locally rare plant species (with lower plant biomass per area) are often smaller with shallower roots than common species (with higher plant biomass per area) in competition-intensive grasslands. Likewise, root feeders are often distributed in the upper soil layers. We hypothesized, therefore, that root feeders would incur negative density (biomass)-dependent damage across plant species. To test this hypothesis, we investigated the diversity and abundance of plant and root feeder species in an alpine meadow and determined the diet of the root feeders using metabarcoding. Across all species, root feeder load decreased with increasing aboveground plant biomass, root biomass, and total plant biomass per area, indicating a negative density dependence of damage across plant species. Aboveground plant biomass per area increased with increasing individual plant biomass and root depth per area across species, suggesting that rare plant species were smaller in size and had shallower root systems compared to common plant species. Both root biomass per area and root feeder biomass per area decreased with soil depth, but the root feeder biomass decreased disproportionately faster compared to root biomass with increasing root depth. Root feeder load decreased with increasing root depth but was not correlated with the feeding preference of root feeder species. Moreover, the prediction derived from a random process incorporating vertical distributions of root biomass and root feeder biomass significantly accounted for interspecific variation in root feeder load. In conclusion, the data indicate that root feeders incur negative density-dependent damage across plant species. On this basis, we suggest that manipulative experiments should be conducted to determine the effect of the negative density-dependent damage on plant community structure and that different types of plant-animal interactions should be concurrently examined to fully understand the effect of plant density on overall herbivore damage across plant species.

Mobile-Delivered Mindfulness Intervention on Anxiety Level Among College Athletes: Randomized Controlled Trial.

BACKGROUND: College athletes are a group often affected by anxiety. Few interventional studies have been conducted to address the anxiety issues in this population. OBJECTIVE: We conducted a mobile-delivered mindfulness intervention among college athletes to study its feasibility and efficacy in lowering their anxiety level and improving their mindfulness (measured by the Five Facet Mindfulness Questionnaire [FFMQ]). METHODS: In April 2019, we recruited 290 college athletes from a public university in Shanghai, China, and 288 of them were randomized into an intervention group and a control group (closed trial), with the former (n=150) receiving a therapist-guided, smartphone-delivered mindfulness-based intervention and the latter receiving mental health promotion messages (n=138). We offered in-person instructions during the orientation session for the intervention group in a classroom, with the therapist interacting with the participants on the smartphone platform later during the intervention. We used generalized linear modeling and the intent-to-treat approach to compare the 2 groups' outcomes in dispositional anxiety, precompetition anxiety, and anxiety during competition, plus the 5 dimensions of mindfulness (measured by the FFMQ). RESULTS: Our intent-to-treat analysis and generalized linear modeling found no significant difference in dispositional anxiety, precompetition anxiety, or anxiety during competition. Only the "observation" facet of mindfulness measures had a notable difference between the changes experienced by the 2 groups, whereby the intervention group had a net gain of .214 yet fell short of reaching statistical significance (P=.09). Participants who specialized in group sports had a higher level of anxiety (ß=.19; SE=.08), a lower level of "nonjudgemental inner experience" in FFMQ (ß=-.07; SE=.03), and a lower level of "nonreactivity" (ß=-.138; SE=.052) than those specializing in individual sports. CONCLUSIONS: No significant reduction in anxiety was detected in this study. Based on the participant feedback, the time availability for mindfulness practice and session attendance for these student athletes in an elite college could have compromised the intervention's effectiveness. Future interventions among this population could explore a more student-friendly time schedule (eg, avoid final exam time) or attempt to improve cognitive and scholastic outcomes. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900024449; https://www.chictr.org.cn/showproj.html?proj=40865.

USP40 promotes hepatocellular carcinoma progression through a YAP/USP40 positive feedback loop.

Yes-associated protein (YAP) is an essential driver of hepatocellular carcinoma (HCC) progression and the ubiquitin-proteasome system controls its abundance. However, the role of ubiquitin-specific protease 40 (USP40) in YAP stability remains unclear. Here, USP40 was first identified as a novel regulator of YAP abundance and its target genes in HCC cells. USP40 interacted with YAP to remove the lysine 48 (K48)-linked polyubiquitination of YAP at K252 and K315 sites, thereby maintaining YAP stability. USP40 facilitated the proliferation, colony formation, migration and spheroid formation of HCC cells in vitro and promoted HCC growth in vivo in a YAP-dependent manner. In turn, YAP transcriptionally activated USP40 expression in HCC cells. RNA sequencing analysis showed that about 37% of USP40-regulated genes overlapped with YAP-regulated genes. Interestingly, stiffness-induced USP40 upregulation was abolished by YAP knockdown, and USP40 knockdown attenuated stiffness-induced YAP accumulation in HCC cells. Clinical data demonstrated that USP40 was positively associated with YAP expression in HCC tissues and its high expression indicated a poor prognosis. In conclusion, the USP40/YAP positive feedback loop contributes to HCC progression, suggesting that USP40 may be a promising drug target for anti-HCC.

[Potential Ecological Risk Assessment of Soil Heavy Metals in Fengdong New District Based on Information Diffution Model].

The large-scale construction of new districts has led to severe soil heavy metal pollution. Therefore, taking Fengdong New District as the target research area, the descriptive statistics of heavy metal content characteristics and Kriging interpolation analysis have been conducted, and the potential ecological risk index and information diffusion theory were further combined to create an information diffusion model based on risk assessment. Finally, the pollution degree, ecological risk, and risk occurrence probability of Pb, Cu, Cd, and Hg were discussed. The findings revealed that the average concentrations of the four heavy metals far exceeded the background value of soil heavy metals by a factor of 1.943 (Pb), 1.419 (Cu), 3.074 (Cd), and 3.567 (Hg), respectively. Moreover, the distribution of soil heavy metals showed strong variability(CV>65%)owing to human interference. The distribution of Pb and Cu pollution were predominantly influenced by industrial production and land development for construction purposes, whereas industrial activities, agricultural practices, and transportation served as the primary sources of Cd contamination. On the other hand, industrial construction emerged as the major factor contributing to Hg pollution. The average values of individual potential ecological risk index for heavy metals of 9.716 (Pb), 7.095 (Cu), 92.292 (Cd), and 142.469 (Hg), coupled with the regional comprehensive potential ecological risk index (RI) average of 251.573, signified that the region was overall characterized by a relatively high potential ecological risk status. The overall potential ecological risk for Pb and Cu in the region were mild, whereas Cd and Hg posed moderate to high risks, indicating that Cd and Hg were the dominant driving factors behind regional heavy metal pollution. The evaluation results of the information diffusion model based on the potential ecological risk indicated that the probability ranking of different levels of comprehensive potential ecological risk was as follows:slightly high (38.98%) > moderate (38.55%) > high (5.89%) > slight (5.15%) > extremely high (3.56%). The exceeding probabilities of potential ecological risk levels for Cd and Hg were significantly higher than those for Pb and Cu. The exceeding probability of different pollution levels of Hg were slight (94.89%), moderate (66.85%), slightly high (23.62%), high (3.9%), and extremely high (2%), of which only the surpassing probability of the slight level was lower than that of Cd. The prediction error of pollution probability of each potential ecological risk level was less than 5%, demonstrating the reliability of the information diffusion model based on the risk assessment. This research will provide technical reference and support for the monitoring and management of potential ecological risks from soil heavy metals in limited sample data regions.

Uncovering rearrangements in the Tibetan antelope via population-derived genome refinement and comparative analysis with homologous species.

Introduction: The Tibetan antelope (Pantholops hodgsonii) is a remarkable mammal thriving in the extreme Qinghai-Tibet Plateau conditions. Despite the availability of its genome sequence, limitations in the scaffold-level assembly have hindered a comprehensive understanding of its genomics. Moreover, comparative analyses with other Bovidae species are lacking, along with insights into genome rearrangements in the Tibetan antelope. Methods: Addressing these gaps, we present a multifaceted approach by refining the Tibetan Antelope genome through linkage disequilibrium analysis with data from 15 newly sequenced samples. Results: The scaffold N50 of the refined reference is 3.2 Mbp, surpassing the previous version by 1.15-fold. Our annotation analysis resulted in 50,750 genes, encompassing 29,324 novel genes not previously study. Comparative analyses reveal 182 unique rearrangements within the scaffolds, contributing to our understanding of evolutionary dynamics and species-specific adaptations. Furthermore, by conducting detailed genomic comparisons and reconstructing rearrangements, we have successfully pioneered the reconstruction of the X-chromosome in the Tibetan antelope. Discussion: This effort enhances our comprehension of the genomic landscape of this species.