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Background: Metabolic dysregulation represents a defining characteristic of Type 2 diabetes (T2DM). Nevertheless, there remains an absence of substantial evidence establishing a direct causal link between circulating blood metabolites and the promotion or prevention of T2DM. In addressing this gap, we employed Mendelian randomization (MR) analysis to investigate the potential causal association between 1,091 blood metabolites, 309 metabolite ratios, and the occurrence of T2DM. Methods: Data encompassing single-nucleotide polymorphisms (SNPs) for 1,091 blood metabolites and 309 metabolite ratios were extracted from a Canadian Genome-wide association study (GWAS) involving 8,299 participants. To evaluate the causal link between these metabolites and Type 2 diabetes (T2DM), multiple methods including Inverse Variance Weighted (IVW), Weighted Median, MR Egger, Weighted Mode, and Simple Mode were employed. p-values underwent correction utilizing False Discovery Rates (FDR). Sensitivity analyses incorporated Cochran's Q test, MR-Egger intercept test, MRPRESSO, Steiger test, leave-one-out analysis, and single SNP analysis. The causal effects were visualized via Circos plot, forest plot, and scatter plot. Furthermore, for noteworthy, an independent T2DM GWAS dataset (GCST006867) was utilized for replication analysis. Metabolic pathway analysis of closely correlated metabolites was conducted using MetaboAnalyst 5.0. Results: The IVW analysis method utilized in this study revealed 88 blood metabolites and 37 metabolite ratios demonstrating a significant causal relationship with T2DM (p < 0.05). Notably, strong causal associations with T2DM were observed for specific metabolites: 1-linoleoyl-GPE (18:2) (IVW: OR:0.930, 95% CI: 0.899-0.962, p = 2.16 × 10-5), 1,2-dilinoleoyl-GPE (18:2/18:2) (IVW: OR:0.942, 95% CI: 0.917-0.968, p = 1.64 × 10-5), Mannose (IVW: OR: 1.133, 95% CI: 1.072-1.197, p = 1.02 × 10-5), X-21829 (IVW: OR:1.036, 95% CI: 1.036-1.122, p = 9.44 × 10-5), and Phosphate to mannose ratio (IVW: OR:0.870, 95% CI: 0.818-0.926, p = 1.29 × 10-5, FDR = 0.008). Additionally, metabolic pathway analysis highlighted six significant pathways associated with T2DM development: Valine, leucine and isoleucine biosynthesis, Phenylalanine metabolism, Glycerophospholipid metabolism, Alpha-Linolenic acid metabolism, Sphingolipid metabolism, and Alanine, aspartate, and glutamate metabolism. Conclusion: This study identifies both protective and risk-associated metabolites that play a causal role in the development of T2DM. By integrating genomics and metabolomics, it presents novel insights into the pathogenesis of T2DM. These findings hold potential implications for early screening, preventive measures, and treatment strategies for T2DM. [ABSTRACT FROM AUTHOR]

A 45-year-old woman presented with right hip pain for a month. Imaging results revealed that the left peritoneal mass was accompanied by metastases of the right sciatic branch, lung, and retroperitoneal lymph nodes. A biopsy of the left peritoneal mass was performed. The pathological morphology demonstrated clear cell adenocarcinoma. Immunohistochemical staining revealed a positive expression of keratin7 and PAX8 and a negative expression of keratin20, GCDFP-15, ER, PR, WT1, CDX2, villin, TTF-1, napsin-A, vimentin, calretinin, and GATA3. Finally, the diagnosis of primary retroperitoneal müllerian adenocarcinoma (PRMA) was confirmed. PRMA is a very rare type of primary retroperitoneal tumor. PRMA should be considered for the retroperitoneal mass. [ABSTRACT FROM AUTHOR]

Background: Despite the efficacy of efgartigimod demonstrated in ADAPT phase 3 trial, data specifically derived from Chinese participants are not available. Therefore, we aimed to evaluate the efficacy and safety of efgartigimod in Chinese patients with generalized myasthenia gravis (gMG). Methods: This is a prospective cohort study conducted in 8 hospitals across China. gMG patients received weekly intravenous infusions of efgartigimod (10  mg/kg) under a named patient program (NPP). The present study is an 8-week study, consisting of 4 consecutive doses of efgartigimod administered over 3  weeks (one cycle), followed by a 5-week follow-up period to assess the tolerability of efgartigimod’s therapeutic effects. The primary outcome was the mean change in MG activities of daily living (MG-ADL) total score from baseline to 4  weeks. MG-ADL responder was defined as a ≥  2-point improvement that persisted for 4  weeks, starting by week 4. Safety evaluations encompassed the monitoring of adverse events (AE) and serious AE (SAE) throughout the study. Results: Between 5 July 2022 and 25 August 2023, a total of 14 gMG patients were included. The mean age was 57.7  years, with a mean MG-ADL score of 10.86  ±  3.32. At week 4, MG-ADL scores showed a mean reduction of 6 points, reaching a maximum decline of 13 points. Among the patients, 85.7% (12/14) achieved MG-ADL responder status after one cycle of treatment. The most significant reduction in quantitative MG (QMG) scores also occurred at week 4, with a mean decrease of 7 points. Notably, the improvements in MG-ADL and QMG scores persisted until week 8. During treatment and follow-up period, only two mild neck rashes occurred and resolved promptly. No infections or SAE were reported. Discussion: A single cycle of efgartigimod treatment demonstrates effectiveness and the tolerability through week 8, with no new safety signals observed in Chinese gMG patients. [ABSTRACT FROM AUTHOR]

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high fatality rate of up to 30% caused by SFTS virus (SFTSV). However, no specific vaccine or antiviral therapy has been approved for clinical use. To develop an effective treatment, we isolated a panel of human monoclonal antibodies (mAbs). SF5 and SF83 are two neutralizing mAbs that recognize two viral glycoproteins (Gn and Gc), respectively. We found that their epitopes are closely located, and we then engineered them as several bispecific antibodies (bsAbs). Neutralization and animal experiments indicated that bsAbs display more potent protective effects than the parental mAbs, and the cryoelectron microscopy structure of a bsAb3 Fab-Gn-Gc complex elucidated the mechanism of protection. In vivo virus passage in the presence of antibodies indicated that two bsAbs resulted in less selective pressure and could efficiently bind to all single parental mAb-escape mutants. Furthermore, epitope analysis of the protective mAbs against SFTSV and RVFV indicated that they are all located on the Gn subdomain I, where may be the hot spots in the phleboviruses. Collectively, these data provide potential therapeutic agents and molecular basis for the rational design of vaccines against SFTSV infection. [ABSTRACT FROM AUTHOR]

Intracellular bacteria are considered to play a key role in the failure of bacterial infection therapy and increase of antibiotic resistance. Nanotechnology-based drug delivery carriers have been receiving increasing attention for improving the intracellular antibacterial activity of antibiotics, but are accompanied by disadvantages such as complex preparation procedures, lack of active targeting, and monotherapy, necessitating further design improvements. Herein, nanoparticles targeting bacteriainfected macrophages are fabricated to eliminate intracellular bacterial infections via antibiotic release and upregulation of intracellular reactive oxygen species (ROS) levels and proinflammatory responses. These nanoparticles were formed through the reaction of the amino group on selenocystamine dihydrochloride and the aldehyde group on oxidized dextran (ox-Dex), which encapsulates vancomycin (Van) through hydrophobic interactions. These nanoparticles could undergo targeted uptake by macrophages via endocytosis and respond to the bacteria-infected intracellular microenvironment (ROS and glutathione (GSH)) for controlled release of antibiotics. Furthermore, these nanoparticles could consume intracellular GSH and promote a significant increase in the level of ROS in macrophages, subsequently up-regulating the proinflammatory response to reinforce antibacterial activity. These nanoparticles can accelerate bacteria-infected wound healing. In this work, nanoparticles were fabricated for bacteria-infected macrophage-targeted and microenvironment-responsive antibiotic delivery, cellular ROS generation, and proinflammatory up-regulation activity to eliminate intracellular bacteria, which opens up a new possibility for multifunctional drug delivery against intracellular infection. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB), caused by the bacterial pathogen Mycobacterium tuberculosis (MTB), remains one of the most prevalent and deadly infectious diseases worldwide. Currently, there are complex interactions between host cells and pathogens in TB. The onset, progression, and regression of TB are correlated not only with the virulence of MTB but also with the immunity of TB patients. Exosomes are cell-secreted membrane-bound nanovesicles with lipid bilayers that contain a variety of biomolecules, such as metabolites, lipids, proteins, and nucleic acids. Exosome-mediated cell--cell communication and interactions with the microenvironment represent crucial mechanisms through which exosomes exert their functional effects. Exosomes harbor a wide range of regulatory roles in physiological and pathological conditions, including MTB infection. Exosomes can regulate the immune response, metabolism, and cellular death to remodel the progression of MTB infection. During MTB infection, exosomes display distinctive profiles and quantities that may act as diagnostic biomarkers, suggesting that exosomes provide a revealing glimpse into the evolving landscape of MTB infections. Furthermore, exosomes derived from MTB and mesenchymal stem cells can be harnessed as vaccine platforms and drug delivery vehicles for the precise targeting and treatment of TB. In this review, we highlight the functions and mechanisms through which exosomes influence the progression of TB. Additionally, we unravel the critical significance of exosomal constituents in the diagnosis and therapeutic applications of TB, aiming to offer novel perspectives and strategies for combating TB. [ABSTRACT FROM AUTHOR]

Under the background of global climate change, Subsurface Marine Heatwaves (SSMHWs) have become a 'hot-spot' research due to their significant impacts on marine ecosystems. Temperature data from the ECCO2 for the years 1992 to 2021 is used to research the spatiotemporal characteristics of SSMHWs in the upper 500 m over the Xisha region (110°E to 113°E, 15°N to 18°N). This study indicates that SSMHWs of high intensity occur in the Xisha area, with the vertical maximum intensity at approximately 100 m. These events exhibit significant seasonal variations, with the highest intensity occurring in May. The intensity of SSMHW in the analysis region varies interannually. SSMHWs have intensified at a rate of 1.53°C·Days/Year and tend to shift to deeper water over the past three decades. A block-based method for SSMHW identification is proposed, in order to take the vertical extent of the event in consideration. By analyzing the eight most intense events based on spatial cumulative intensity, it suggested that warm mesoscale eddies may play an important role on the spatial distribution of the SSMHWs. Statistical analysis shows that the intensity and coverage of the warm mesoscale eddy in the Xisha zone may influence the intensity and evolution of the SSMHWs. Additionally, only 18.27% of SSMHW events occur with apparent surface marine heatwave signals. These findings are vital for uncovering SSMHW dynamics in the Xisha area, and are important for future monitoring, early warnings and marine conservation. [ABSTRACT FROM AUTHOR]

Introduction: Bone metastases are associated with increased morbidity and decreased quality of life in patients with solid tumors. Identifying patients at increased risk of bone metastases at diagnosis could lead to earlier interventions. We sought to retrospectively identify the incidence and predictive factors for bone metastases at initial diagnosis in a large population-based dataset. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients 18 years-old or older diagnosed with solid cancers from 2010 to 2019. Patients with hematologic malignancies and primary tumors of the bone were excluded. We calculated the incidence and predictive factors for bone metastases according to demographic and tumor characteristics. Results: Among 1,132,154 patients identified, 1,075,070 (95.0%) had known bone metastasis status andwere eligible for the study. Bonemetastaseswere detected in 55,903 patients (5.2% of those with known bone metastases status). Among patients with bone metastases, the most common primary tumors arose from lung (44.4%), prostate (19.3%), breast (12.3%), kidney (4.0%), and colon (2.2%). Bone metastases at presentation were most common in small cell lung cancer (25.2%), non-small cell lung cancer (18.0%), and esophageal adenocarcinoma (9.4%). In addition to stage classification, predictors for bone metastases included Gleason score (OR 95.7 (95% CI 73.1 - 125.4) for Grade Group 5 vs 1 and OR 42.6 (95% CI 32.3 - 55.9) for Group 4 vs 1) and PSA (OR 14.2 (95% CI 12.6 - 16.0) for PSA > 97 vs 0 - 9.9) for prostate cancer, HER2 and hormonal receptor (HR) status (OR 2.2 (95% CI 1.9 - 2.6) for HR+/HER2+ vs HR-/HER2-) for breast cancer, histology (OR 2.5 (95% CI 2.3 - 2.6) for adenocarcinoma vs squamous) for lung cancer, and rectal primary (OR 1.2 (95% 1.1 - 1.4) vs colon primary) and livermetastases (OR 8.6 (95% CI 7.3 - 10.0) vs no liver metastases) for colorectal tumors. Conclusions: Bone metastases at presentation are commonly seen in solid tumors, particularly lung, prostate, breast, and kidney cancers. Clinical and pathologic factors are associated with a significantly increased risk for bone metastases. [ABSTRACT FROM AUTHOR]

Porcine idiopathic vesicular disease (PIVD), one of several clinically indistinguishable vesicular diseases of pigs, is caused by the emerging pathogen Senecavirus A (SVA). Despite the widespread prevalence of porcine SVA infection, no effective commercial vaccines for PIVD prevention and control are available, due to high costs associated with vaccine testing in pigs, considerable SVA diversity, and SVA rapid evolution. In this study, SVA CH/JL/2022 (OP562896), a novel mutant SVA strain derived from an isolate obtained from a pig farm in Jilin Province, China, was inactivated then combined with four adjuvants, MONTANIDETM GEL02 PR (GEL 02), MONTANIDETM ISA 201 VG (ISA 201), MONTANIDETM IMG 1313 VG N (IMS1313), or Rehydragel LV (LV). The resulting inactivated SVA CH/JL/2022 vaccines were assessed for efficacy in mice and found to induce robust in vivo lymphocyte proliferation responses and strong IgG1, IgG2a, and neutralizing antibody responses with IgG2a/IgG1 ratios of <1. Furthermore, all vaccinated groups exhibited significantly higher levels of serum cytokines IL-2, IL-4, IL-6, and IFN as compared to unvaccinated mice. These results indicate that all vaccines elicited both Th1 and Th2 responses, with Th2 responses predominating. Moreover, vaccinated mice exhibited enhanced resistance to SVA infection, as evidenced by reduced viral RNA levels and SVA infection-induced histopathological changes. Collectively, our results demonstrate that the SVA-GEL vaccine induced more robust immunological responses in mice than did the other three vaccines, thus highlighting the potential of SVA-GEL to serve an effective tool for preventing and controlling SVA infection. [ABSTRACT FROM AUTHOR]

Background Endovascular therapy administered within 24 hours has been shown to improve outcomes for patients with acute ischemic stroke with large infarction, but the data on its cost-effectiveness are limited. Objective To evaluate the cost-effectiveness of endovascular therapy for acute ischemic stroke with large infarction in China, the largest low- and middle-income country. Methods A short-term decision tree model and a long-term Markov model were used to analyze the cost-effectiveness of endovascular therapy for patients with acute ischemic stroke with large infarction. Outcomes, transition probability, and cost data were obtained from a recent clinical trial and published literature. The benefit of endovascular therapy was assessed by the cost per quality-adjusted life-years (QALYs) gained in the short and long term. Deterministic one-way and probabilistic sensitivity analyses were performed to assess the robustness of the results. Results Compared with medical management alone, endovascular therapy for acute ischemic stroke with large infarction was found to be cost-effective from the fourth year onward and during a lifetime. In the long term, endovascular therapy yielded a lifetime gain of 1.33 QALYs at an additional cost of ¥73 900 (US$ 11 400), resulting in an incremental cost of ¥55 500 (US$ 8530) per QALY gained. Probabilistic sensitivity analysis showed that endovascular therapy was cost-effective in 99.5% of the simulation runs at a willingness-to-pay threshold of ¥243 000 (3 x gross domestic product per capita of China in 2021) per QALY gained. Conclusions Endovascular therapy for acute ischemic stroke with large infarction could be cost-effective in China. [ABSTRACT FROM AUTHOR]

The quality of the bimetal produced by explosion welding is affected by the mechanical characteristics of flying plate material. For development of explosion welding modes, a study of the structure and mechanical properties of titanium alloy Grade 12 (TA10, flying plate) + carbon steel 16 Mn (09G2S) bimetal was conducted. The thickness of the titanium alloy plates was 5 and 6 mm, the mechanical properties, namely the relative elongation in as-delivered condition for these plates differed by 15 %. The results on tear and shear strength of titanium alloy-carbon steel bimetal are given. In the case of titanium alloy TA 10 it is demonstrated that for plates with a lower relative elongation, the strength of the joint produced by explosion welding is lower. Bending test showed no delamination for two thicknesses of the titanium alloy. Also, for the two thicknesses of the titanium alloy, the joint zone has a microstructure characteristic for explosion welding. [ABSTRACT FROM AUTHOR]

Recent evidence has demonstrated that the transsynaptic nanoscale organization of synaptic proteins plays a crucial role in regulating synaptic strength in excitatory synapses. However, the molecular mechanism underlying this transsynaptic nanostructure in inhibitory synapses still remains unclear and its impact on synapse function in physiological or pathological contexts has not been demonstrated. In this study, we utilized an engineered proteolysis technique to investigate the effects of acute cleavage of neuroligin- 2 (NL2) on synaptic transmission. Our results show that the rapid cleavage of NL2 led to impaired synaptic transmission by reducing both neurotransmitter release probability and quantum size. These changes were attributed to the dispersion of RIM1/2 and GABAA receptors and a weakened spatial alignment between them at the subsynaptic scale, as observed through superresolution imaging and model simulations. Importantly, we found that endogenous NL2 undergoes rapid MMP9- dependent cleavage during epileptic activities, which further exacerbates the decrease in inhibitory transmission. Overall, our study demonstrates the significant impact of nanoscale structural reorganization on inhibitory transmission and unveils ongoing modulation of mature GABAergic synapses through active cleavage of NL2 in response to hyperactivity. [ABSTRACT FROM AUTHOR]

An ideal thermoelectric material requires the multi-valley and strong dispersion band structure, for relieving the competition between thermopower and electrical conductivity, whereas the two features barely coexist in natural compounds. Here, the significantly improved thermoelectric performance in n-type PbSe-xAgSbS2 with the purposefully renormalized conduction band structure is reported. It is shown that the strong spin-orbit coupling effect splits the single valley at "L" point into three individuals delicately, as the Dirac point is shifted away from the high symmetry point by the decreasing lattice constant. Compared with the common PbSe-based compounds, the renormalized system exhibits a range of distinctive properties, such as the 2-3 times larger band gap, 5-10 times lower optimal carrier concentration, and weakly temperature-dependent Seebeck coefficient. Owing to the achieved giant band convergence and the low thermal conductivity, a high peak zT of 1.75 at 850 K and an outstanding average zT of 1.04 are obtained. Furthermore, the mechanical property and thermal stability of PbSe are considerably improved for the introduced high entropy effect and lattice shrinkage. This study reveals the remarkable impact of spin-orbit coupling on thermoelectric performance, and suggests that the optimized PbSe material holds great promise for practical applications. [ABSTRACT FROM AUTHOR]

Purpose: To compare the prognosis of complete and insufficient ablation of transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in treating medium and large hepatocellular carcinoma (HCC) and to explore the differences in recurrence patterns between the two groups. Patients and methods: Patients' medical records and imaging data of patients with confirmed HCC from January 2014 to January 2022 were collected. These patients were divided into 2 groups: complete ablation (n=172) and insufficient ablation (n=171). Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier curve and the log-rank test was used to compared. Fisher's exact test was used to compare recurrence patterns between the two groups. Results: The median OS time was 72.8 months (95%CI:69.5-76.1) and 62.0 months (95%CI: 55.3-68.7) in the complete and insufficient ablation groups, respectively. The median PFS time in the complete ablation group was 67.8 months (95% CI: 65.2-70.4) and 38.6 months (95%CI: 29.8-47.4) in the insufficient ablation group. The OS and PFS rates of the complete ablation group were significantly better than those of the insufficient ablation group (P<0.001). In the complete ablation group, 25(41%) patients experienced local tumor progression(LTP), 36(59%) experienced intrahepatic distant progression (IDP), and 0(0%) experienced extrahepatic progression (EP). In the insufficient ablation group, 51 (32.1%) patients experienced LTP, 96 (60.4%) experienced IDP, and 12 (7.5%) experienced EP. The progression patterns of the two groups were statistically significant (P=0.039). Conclusion: Insufficient ablation indicates a poor survival outcome of TACE combined with RFA for medium and large HCC and can promote intrahepatic distant and extrahepatic metastasis. [ABSTRACT FROM AUTHOR]

Introduction: Spinal cord injury (SCI) is a severely disabling disease. Hyperactivation of neuroinflammation is one of the main pathophysiological features of secondary SCI, with phospholipid metabolism playing an important role in regulating inflammation. Phospholipase D (PLD), a critical lipid-signaling molecule, is known to be involved in various physiological processes, including the regulation of inflammation. Despite this knowledge, the specific role of PLD in SCI remains unclear. Methods: In this study, we constructed mouse models of SCI and administered PLD inhibitor (FIPI) treatment to investigate the efficacy of PLD. Additionally, transcriptome sequencing and protein microarray analysis of spinal cord tissues were conducted to further elucidate its mechanism of action. Results: The results showed that PLD expression increased after SCI, and inhibition of PLD significantly improved the locomotor ability, reduced glial scarring, and decreased the damage of spinal cord tissues in mice with SCI. Transcriptome sequencing analysis showed that inhibition of PLD altered gene expression in inflammation regulation. Subsequently, the protein microarray analysis of spinal cord tissues revealed variations in numerous inflammatory factors. Biosignature analysis pointed to an association with immunity, thus confirming the results obtained from transcriptome sequencing. Discussion: Collectively, these observations furnish compelling evidence supporting the anti-inflammatory effect of FIPI in the context of SCI, while also offering important insights into the PLD function which may be a potential therapeutic target for SCI. [ABSTRACT FROM AUTHOR]

Autoimmune encephalitis (AE) broadly refers to inflammation of the brain parenchyma mediated by autoimmune mechanisms. In most patients with AE, autoantibodies against neuronal cell surface antigens are produced by B-cells and induce neuronal dysfunction through various mechanisms, ultimately leading to disease progression. In recent years, B-cell targeted therapies, including monoclonal antibody (mAb) therapy and chimeric antigen receptor T-cell (CAR-T) therapy, have been widely used in autoimmune diseases. These therapies decrease autoantibody levels in patients and have shown favorable results. This review summarizes the mechanisms underlying these two B-cell targeted therapies and discusses their clinical applications and therapeutic potential in AE. Our research provides clinicians with more treatment options for AE patients whose conventional treatments are not effective. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) results in a large amount of tissue cell debris in the lesion site, which interacts with various cytokines, including inflammatory factors, and the intrinsic glial environment of the central nervous system(CNS) to forman inhibitory microenvironment that impedes nerve regeneration. The efficient clearance of tissue debris is crucial for the resolution of the inhibitory microenvironment after SCI. Macrophages are themain cells responsible for tissue debris removal after SCI. However, the high lipid content in tissue debris and the dysregulation of lipid metabolism within macrophages lead to their transformation into foamy macrophages during the phagocytic process. This phenotypic shift is associated with a further pro-inflammatory polarization that may aggravate neurological deterioration and hamper nerve repair. In this review, we summarize the phenotype and metabolism of macrophages under inflammatory conditions, as well as the mechanisms and consequences of foam cell formation after SCI. Moreover, we discuss two strategies for foamcell modulation and several potential therapeutic targets that may enhance the treatment of SCI. [ABSTRACT FROM AUTHOR]

Introduction: Behaviors of swimming rodents are not uniform, exhibiting large variations, which may underlie the individual differences in swimming exerciseinduced benefits. The study aimed to monitor individualized swimming behavior and evaluate its biological significance. Methods: A swimming tank which can monitor individualized rodent swimming behavior during exercise was established. A total of 45 mice were subjected to swimming training for 1 month (1 h per day) and the swimming behaviors of each mouse were recorded. Results: The swimming behaviors of mice displayed considerable variations in aspects of distance, velocity, and area preference. For example, nearly one-third of mice preferred to swim in central area and most of the mice exhibited an even area distribution. Long-term exercise training improved cardiac systolic function and decreased blood pressure in mice, but hardly changed swimming behaviors. Analyses of the relationship between swimming behavior and cardiovascular adaptations to exercise training revealed that swimming behavior indicated the biological effects of swimming training. Specifically, mice which preferred swimming at the central zone or were trainable in behavior during 1-month training exhibited better outcomes in cardiac function and blood pressure post long-term exercise. Mechanistically, a centralized swimming behavior indicated a smaller stress during exercise, as evidenced by a milder activation of hypothalamic-pituitary-adrenal axis. Discussion: These results suggest that swimming behavior during training indicates individualized adaptations to long-term exercise, and highlight a biological significance of swimming behavior monitoring in animal studies. [ABSTRACT FROM AUTHOR]

Background The latent and incubation periods characterize the transmission of infectious viruses and are the basis for the development of outbreak prevention and control strategies. However, systematic studies on the latent period and associated factors with the incubation period for SAS-CoV-2 variants are still lacking. We inferred the two durations of Delta, BA.1, and BA.2 cases and analyzed the associated factors. Methods The Delta, BA.1, and BA.2 (and its lineages BA.2.2 and BA.2.76) cases with clear transmission chains and infectors from 10 local SAS-CoV-2 epidemics in China were enrolled. The latent and incubation periods were fitted by the Gamma distribution, and associated factors were analyzed using the accelerated failure time model. Results The mean latent period for 672 Delta, 208 BA.1, and 677 BA.2 cases was 4.40 (95%CI: 4.24~4.63), 2.50 (95%CI: 2.27~2.76), and 2.58 (95%CI: 2.48~2.69) days, respectively, with 85.65% (95%CI: 83.40~87.77%), 97.80% (95%CI: 96.35~98.89%), and 98.87% (95%CI: 98.40~99.27%) of them starting to shed viruses within 7 days after exposure. In 405 Delta, 75 BA.1, and 345 BA.2 symptomatic cases, the mean latent period was 0.76, 1.07, and 0.79 days shorter than the mean incubation period [5.04 (95%CI: 4.83~5.33), 3.42 (95%CI: 3.00~3.89), and 3.39 (95%CI: 3.24~3.55) days], respectively. No significant difference was observed in the two durations between BA.1 and BA.2 cases. After controlling for the sex, clinical severity, vaccination history, number of infectors, the length of exposure window and shedding window, the latent period [Delta: exp(β)=0.81, 95%CI: 0.66~0.98, p=0.034; Omicron: exp(β)=0.82, 95%CI: 0.71~0.94, p=0.004] and incubation period [Delta: exp(β)=0.69, 95%CI: 0.55~0.86, p<0.001; Omicron: exp(β)=0.83, 95%CI: 0.72~0.96, p=0.013] were significantly shorter in 18~49 years but did not change significantly in ≥50 years compared with 0~17 years. Conclusion Pre-symptomatic transmission can occur in Delta, BA.1, and BA.2 cases. The latent and incubation periods between BA.1 and BA.2 were similar but shorter compared with Delta. Age may be associated with the latent and incubation periods of SARS-CoV-2 [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Biochemistry is the property of Society of Medical Biochemists of Serbia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Significance: The conventional optical properties (OPs) reconstruction in spatial frequency domain (SFD) imaging, like the lookup table (LUT) method, causes OPs aliasing and yields only average OPs without depth resolution. Integrating SFD imaging with time-resolved (TR) measurements enhances space-TR information, enabling improved reconstruction of absorption (μa) and reduced scattering (μ's) coefficients at various depths. Aim: To achieve the stratified reconstruction of OPs and the separation between μa and μ's, using deep learning workflow based on the temporal and spatial information provided by time-domain SFD imaging technique, while enhancing the reconstruction accuracy. Approach: Two data processing methods are employed for the OPs reconstruction with TR-SFD imaging, one is full TR data, and the other is the featured data extracted from the full TR data (E, continuous-wave component, (t), mean time of flight). We compared their performance using a series of simulation and phantom validations. Results: Compared to the LUT approach, utilizing full TR, E and (t) datasets yield high-resolution OPs reconstruction results. Among the three datasets employed, full TR demonstrates the optimal accuracy. Conclusions: Utilizing the data obtained from SFD and TR measurement techniques allows for achieving high-resolution separation reconstruction of μa and μ's at different depths within 5 mm. [ABSTRACT FROM AUTHOR]

Background. Biochar amendments enhance crop productivity and improve agricultural quality. To date, studies on the correlation between different amounts of biochar in pakchoi (Brassica campestris L.) quality and rhizosphere soil microorganisms are limited, especially in weakly alkaline soils. The experiment was set up to explore the effect of different concentrations of biochar on vegetable quality and the correlation between the index of quality and soil bacterial community structure changes. Methods. The soil was treated in the following ways via pot culture: the blank control (CK) without biochar added and with biochar at different concentrations of 1% (T1), 3%(T2),5%(T3), and7%(T4). Here, we investigatedthe synergistic effect of biochar on the growth and quality of pakchoi, soil enzymatic activities, and soil nutrients. Microbial communities from pakchoi rhizosphere soil were analyzed by Illumina MiSeq. Results. The results revealed that adding 3% biochar significantly increased plant height, root length, and dry weight of pakchoi and increased the contents of soluble sugars, soluble proteins, Vitamin C (VC), cellulose, and reduced nitrate content in pakchoi leaves. Meanwhile, soil enzyme activities and available nutrient content in rhizosphere soil increased. This study demonstrated that the the microbial community structure of bacteria in pakchoi rhizosphere soil was changed by applying more than 3% biochar. Among the relatively abundant dominant phyla, Gemmatimonadetes, Anaerolineae, Deltaproteobacteria and Verrucomicrobiae were reduced, and Alphaproteobacteria, Gammaproteobacteria, Bacteroidia, and Acidimicrobiia relative abundance increased. Furthermore, adding 3% biochar reduced the relative abundance of Gemmatimonas and increased the relative abundances of Ilumatobacter, Luteolibacter, Lysobacter, Arthrobacter, and Mesorhizobium. The nitrate content was positively correlated with the abundance of Gemmatimonadetes, and the nitrate content was significantly negatively correlated with the relative abundance of Ilumatobacter. Carbohydrate transport and metabolism in the rhizosphere soil of pakchoi decreased, and lipid transport and metabolism increased after biochar application. Conclusion. Overall, our results indicated that applying biochar improved soil physicochemical states and plant nutrient absorption, and affected the abundance of dominant bacterial groups (e.g., Gemmatimonadetes and Ilumatobacter), these were the main factors to increase pakchoi growth and promote quality of pakchoi. Therefore, considering the growth, quality of pakchoi, and soil environment, the effect of using 3% biochar is better. [ABSTRACT FROM AUTHOR]

Background and purpose: Adjunctive tirofiban administration in patients undergoing endovascular treatment (EVT) for acute large vessel occlusion (LVO) has been investigated in several studies. However, the findings are conflict. This study aimed to compare the eect of dierent administration pathways of tirofiban on patients undergoing EVT for acute LVO with intracranial atherosclerotic disease (ICAD). Methods: Patients were selected from the ANGEL-ACT Registry (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke: A Prospective Multicenter Registry Study) and divided into four groups: intra-arterial (IA), intravenous (IV), and intra-arterial plus intravenous (IA+IV) and non-tirofiban. The primary outcome was 90-day ordinal modified Rankin Scale (mRS) score, and the secondary outcomes included the rates of mRS 0–1, 0–2, and 0–3 at 90-day, successful recanalization. The safety outcomes were symptomatic intracranial hemorrhage (sICH) and other safety endpoints. The multivariable logistic regression models adjusting for potential baseline confounders were performed to compare the outcomes. A propensity score matching (PSM) with a 1:1:1:1 ratio was conducted among four groups, and the outcomes were then compared in the post-matched population. Results: A total of 502 patients were included, 80 of which were in the IAtirofiban group, 73 in IV-tirofiban, 181 in (IA+IV)-tirofiban group, and 168 in the non-tirofiban group. The median (IQR) 90-day mRS score in the four groups of IA, IV, IA+IV, and non-tirofiban was, respectively 3(0–5) vs. 1(0–4) vs. 1(0–4) vs. 3(0–5). The adjusted common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.77 (95% CI, 0.45–1.30, P = 0.330), with IV-tirofiban vs. non-tirofiban was 1.36 (95% CI, 0.78–2.36, P = 0.276), and with (IA+IV)-tirofiban vs. non-tirofiban was 1.03 (95% CI, 0.64–1.64, P = 0.912). The adjusted OR for mRS 0–1 and mRS 0–2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.51 (95% CI, 0.27–0.98, P = 0.042) and 0.50 (95% CI, 0.26–0.94, P = 0.033). The other outcomes of each group were similar with non-tirofiban group, all P was >0.05. After PSM, the common odds ratio (OR) for 90-day ordinal modified Rankin Scale distribution with IA-tirofiban vs. non-tirofiban was 0.41 (95% CI, 0.18–0.94, P = 0.036), and the OR for mRS 0–1 and mRS 0–2 at 90-day with IA-tirofiban vs. non-tirofiban was, respectively 0.28 (95% CI, 0.11–0.74, P = 0.011) and 0.25 (95% CI, 0.09–0.67, P = 0.006). Conclusions: Intra-arterial administration of tirofiban was associated with worse outcome than non-tirofiban, which suggested that intra-arterial tirofiban had a harmful eect on patients undergoing EVT for ICAD-LVO. [ABSTRACT FROM AUTHOR]

Orf virus (ORFV), a typical member of the genus Parapoxvirus, Poxvirus family, causes a contagious pustular dermatitis in sheep, goats, and humans. Poxviruses encode a multisubunit DNA-dependent RNA polymerase (vRNAP) that carries out viral gene expression in the host cytoplasm, which is a viral factor essential to poxvirus replication. Due to its vital role in viral life, vRNAP has emerged as one of the potential drug targets. In the present study, we investigated the antiviral effect of genistein against ORFV infection. We provided evidence that genistein exerted antiviral effect through blocking viral genome DNA transcription/replication and viral protein synthesis and reducing viral progeny, which were dosedependently decreased in genistein-treated cells. Furthermore, we identified that genistein interacted with the vRNAP RPO30 protein by CETSA, molecular modeling and Fluorescence quenching, a novel antiviral target for ORFV. By blocking vRNAP RPO30 protein using antibody against RPO30, we confirmed that the inhibitory effect exerted by genistein against ORFV infection is mediated through the interaction with RPO30. In conclusion, we demonstrate that genistein effectively inhibits ORFV transcription in host cells by targeting vRNAP RPO30, which might be a promising drug candidate against poxvirus infection. [ABSTRACT FROM AUTHOR]

Spinal cord injury is a severe neurological trauma that can frequently lead to neuropathic pain. During the initial stages following spinal cord injury, inflammation plays a critical role; however, excessive inflammation can exacerbate pain. Regulatory T cells (Treg cells) have a crucial function in regulating inflammation and alleviating neuropathic pain. Treg cells release suppressor cytokines and modulate the function of other immune cells to suppress the inflammatory response. Simultaneously, inflammation impedes Treg cell activity, further intensifying neuropathic pain. Therefore, suppressing the inflammatory response while enhancing Treg cell regulatory function may provide novel therapeutic avenues for treating neuropathic pain resulting from spinal cord injury. This review comprehensively describes the mechanisms underlying the inflammatory response and Treg cell regulation subsequent to spinal cord injury, with a specific focus on exploring the potential mechanisms through which Treg cells regulate neuropathic pain following spinal cord injury. The insights gained from this review aim to provide new concepts and a rationale for the therapeutic prospects and direction of cell therapy in spinal cord injury-related conditions. [ABSTRACT FROM AUTHOR]

Microbial interactions are key to maintaining soil biodiversity. However, whether negative or positive associations govern the soil microbial system at a global scale remains virtually unknown, limiting our understanding of how microbes interact to support soil biodiversity and functions. Here, we explored ecological networks among multitrophic soil organisms involving bacteria, protists, fungi, and invertebrates in a global soil survey across 20 regions of the planet and found that positive associations among both pairs and triads of soil taxa governed global soil microbial networks. We further revealed that soil networks with greater levels of positive associations supported larger soil biodiversity and resulted in lower network fragility to withstand potential perturbations of species losses. Our study provides unique evidence of the widespread positive associations between soil organisms and their crucial role in maintaining the multitrophic structure of soil biodiversity worldwide. [ABSTRACT FROM AUTHOR]

Ascites and pleural effusion are recognized complications of pancreatic cancer. These diseases are accompanied by ascites and pleural effusion, and drug treatment is limited by high costs, long hospital stays, and failure rates. Immunotherapy may offer new option, but in most patients with late stages of cancer, immune cells may lose the ability to recognize tumor cells, how to activate their immune cells is a major problem, sodium glucosidate (SSG) is injected into ascites as a protein tyrosine phosphatase inhibitor to wake up immune cells and prepare for immunotherapy. We used single-cell RNA sequencing (scRNA-seq) to investigate whether and how SSG injected into ascites of pancreatic cancer elicits an immune response. Our study showed that the process of SSG fusion treatment of ascites and pleural effusion, the interaction between TandNK cells, MPs cells, monocytes and neutrophils was induced, and large numbers of genes were expressed, resulting in upregulation of immune response, which also approved that SSG is not only used as a protein tyrosine phosphatase inhibitor, but also it works as a protein tyrosine phosphatase inhibitor. It can also be used to regulate immune cell function, recruiting immune cells to the right place with the help of PD-1 or PD-L1 to fight cancer cells in ascites and pleural effusions in cancer patients. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is a toxic, essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter. These studies have mainly focused on the production and pharmacological side effects caused by H2S. Therefore, effective strategies to remove H2S has become a key research topic. Furthermore, the development of novel nanoplatforms has provided new tools for the targeted removal of H2S. This paper was performed to review the association between H2S and disease, related H2S inhibitory drugs, as well as H2S responsive nanoplatforms (HRNs). This review first analyzed the role of H2S in multiple tissues and conditions. Second, common drugs used to eliminate H2S, as well as their potential for combination with anticancer agents, were summarized. Not only the existing studies on HRNs, but also the inhibition H2S combined with different therapeutic methods were both sorted out in this review. Furthermore, this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail. Finally, potential challenges of HRNs were proposed. This study demonstrates the excellent potential of HRNs for biomedical applications. [ABSTRACT FROM AUTHOR]

Let H be a complex infinite dimensional Hilbert space and B (H) be the algebra of all bounded linear operators on H . In this paper, we mainly study the operators that satisfy both a-Weyl's theorem and property (R). Also, the operators whose functional calculus satisfies the two properties are also explored. We give the features for the operator or its functional calculus for which both a-Weyl's theorem and property (R) hold. [ABSTRACT FROM AUTHOR]

Purpose: To explore the epidemiological trends in acetabular fracture and report the mid-term to long-term clinical outcomes of the elderly treated with operation. Methods: Retrospective study. Patients aged ≥ 14 years with operative treatment of the Acetabular fracture from Jan 2010 to Dec 2019 at a level-1 trauma centre were identified to analyze the epidemiological trends, and the difference in fracture patterns between young and elderly patients (≥ 60 years old) were compared. The elderly patients were followed up to evaluate their clinical outcomes and satisfaction degree (worst to best: 0 to10). The patients were divided into the 2010–2014 group and the 2015–2019 group according to the year of admission, and the clinical outcomes of the two groups were compared to verify the stability from mid-term to long-term after surgery for acetabular fracture. Results: A total of 1024 patients (mean age 43.35 years, range 14–86 years) with acetabular fractures received operative treatment in this decade. The mean age of the acetabular fracture patients increased from 41.1 years to 47.7 years, and the proportion of elderly patients increased from 5.7% to 24.0%, with some volatility. The ratio of male to female decreased year by year, and the proportion of female patients increased with age. And the anterior fracture patterns were more common in the elderly patients compared to the young patients (P < 0.001). 118 elderly patients (82 males, 36 females; mean age 66.91 years, range 60–86 years) were followed-up (mean 77.4 months, range 35–152 months). The overall mortality rate of the elderly patients was 7.69% (9/118). The Harris hip score of those alive patients was 90.41 ± 12.91 points (excellent and good rate 84.4%). 87 patients completed the SF-12 with a normal HRQoL (PCS 50.49 ± 8.88 points; MCS 55.66 ± 8.86 points). 90.8% of the patients achieved a satisfaction score of 9 or higher. And there was no significant difference in clinical outcomes between the 2010–2014 group and the 2015–2019 group (P > 0.05). Conclusions: In conclusion, acetabular fractures presented an obvious ageing trend in China, and the fracture patterns of the elderly patients differed from those in the young patients. Operative treatment for elderly acetabular fractures yielded satisfactory and persistent clinical outcomes from mid-term to long-term clinical. [ABSTRACT FROM AUTHOR]

Background: Multidisciplinary team (MDT) meetings are the gold standard of cancer treatment. However, the limited participation of multiple medical experts and the low frequency of MDT meetings reduce the efficiency and coverage rate of MDTs. Herein, we retrospectively report the results of an asynchronous MDT based on a cloud platform (cMDT) to improve the efficiency and coverage rate of MDT meetings for digestive tract cancer. Methods: The participants and cMDT processes associated with digestive tract cancer were discussed using a cloud platform. Software programming and cMDT test runs were subsequently conducted to further improve the software and processing. cMDT for digestive tract cancer was officially launched in June 2019. The doctor response duration, cMDT time, MDT coverage rate, National Comprehensive Cancer Network guidelines compliance rate for patients with stage III rectal cancer, and uniformity rate of medical experts’ opinions were collected. Results: The final cMDT software and processes used were determined. Among the 7462 digestive tract cancer patients, 3143 (control group) were diagnosed between March 2016 and February 2019, and 4319 (cMDT group) were diagnosed between June 2019 and May 2022. The average number of doctors participating in each cMDT was 3.26 ± 0.88. The average doctor response time was 27.21 ± 20.40 hours, and the average duration of cMDT was 7.68 ± 1.47 min. The coverage rates were 47.85% (1504/3143) and 79.99% (3455/4319) in the control and cMDT groups, respectively. The National Comprehensive Cancer Network guidelines compliance rates for stage III rectal cancer patients were 68.42% and 90.55% in the control and cMDT groups, respectively. The uniformity rate of medical experts’ opinions was 89.75% (3101/3455), and 8.97% (310/3455) of patients needed online discussion through WeChat; only 1.28% (44/3455) of patients needed face-to-face discussion with the cMDT group members. Conclusion: A cMDT can increase the coverage rate of MDTs and the compliance rate with National Comprehensive Cancer Network guidelines for stage III rectal cancer. The uniformity rate of the medical experts’ opinions was high in the cMDT group, and it reduced contact between medical experts during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is caused by the bacterial pathogen Mycobacterium tuberculosis (MTB) and is one of the principal reasons for mortality and morbidity worldwide. Currently, recommended anti-tuberculosis drugs include isoniazid, rifampicin, ethambutol, and pyrazinamide. TB treatment is lengthy and inflicted with severe side-effects, including reduced patient compliance with treatment and promotion of drug-resistant strains. TB is also prone to other concomitant diseases such as diabetes and HIV. These drug-resistant and complex co-morbid characteristics increase the complexity of treating MTB. Host-directed therapy (HDT), which effectively eliminates MTB and minimizes inflammatory tissue damage, primarily by targeting the immune system, is currently an attractive complementary approach. The drugs used for HDT are repositioned drugs in actual clinical practice with relative safety and efficacy assurance. HDT is a potentially effective therapeutic intervention for the treatment of MTB and diabetic MTB, and can compensate for the shortcomings of current TB therapies, including the reduction of drug resistance and modulation of immune response. Here, we summarize the state-of-the-art roles and mechanisms of HDT in immune modulation and treatment of MTB, with a special focus on the role of HDT in diabetic MTB, to emphasize the potential of HDT in controlling MTB infection. [ABSTRACT FROM AUTHOR]

Background: It has been discovered that Janus kinase 2 (JAK2) exon12 mutations lead to the polycythemia vera (PV) phenotype, while somatic mutations of calreticulin (CALR) are associated with essential thrombocythemia (ET) or primary myelofibrosis. In this article, we report a case of ET with coexistence of JAK2 exon12 and CALR mutations. The objective of this study was to elucidate the pathogenicity mechanism of a JAK2 exon12 mutation (JAK2N533S) and the role of the coexistence of mutations on the hematological phenotype. Methods: We designed a colony analysis of tumor cells obtained from this patient, and attempted to identify mutant genes using DNA from hair follicles. Mutation impairment prediction and conservative analysis were conducted to predict the mutation impairment and structure of JAK2N533S. In addition, we conducted a functional analysis of JAK2N533S by constructing Ba/F3 cell models. Results: Three distinct tumor subclones, namely JAK2N533Shet+/CALRtype1het+, JAK2N533Shet+/CALRwt, and JAK2N533Shet+/CALRtype1hom+, were identified from the 17 selected erythroid and 21 selected granulocyte colonies. The analysis of hair follicles yielded positive results for JAK2N533S. According to the bioinformatics analysis, JAK2N533S may exert only a minor effect on protein function. Functional studies showed that JAK2N533S did not have a significant effect on the proliferation of Ba/F3 cells in the absence of interleukin-3 (IL-3), similar to wild-type JAK2. Notably, there were no increased phosphorylation levels of JAK2-downstream signaling proteins, including signal transducer and activator of transcription 3 (STAT3) and STAT5, in Ba/F3 cells harboring the JAK2N533S. Conclusion: Our study revealed that the JAK2N533Shet+/CALRtype1het+ subclone was linked to a significant expansion advantage in this patient, indicating that it may contribute to the development of the ET phenotype. We further demonstrated that JAK2N533S, as a noncanonical JAK2 exon12 mutation, is a germline mutation that may not exert an effect on cell proliferation and protein function. These results and the present body of available data imply that certain noncanonical JAK2 mutations are not gain-of-function mutations leading to the development of myeloproliferative neoplasms. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is one of the most common and deadly cancers in women, which is closely linked to the persistent infection of high-risk human papillomavirus (HPV). Current treatment of cervical cancer involves radical hysterectomy, radiotherapy, and chemotherapy or a combination. Objective: We investigated if hapten-enhanced intratumoral chemotherapy (HEIC) was effective in boosting immunity for effective treatment of precancerous cervical lesions and HPV infection. Study design: We used single-cell RNA sequencing (scRNA-Seq) to obtain transcriptome profiles of 40,239 cells from biopsies of precancerous cervical lesions from the cervix directly from one patient before the start of HEIC and approximately 1 week after HEIC. The blood samples were taken at the same time as biopsies. We compared the expression characteristics of malignant epithelial cells and immune cells, including epithelial cells, endothelial cells (ECs), fibroblasts, mural cells, T cells, B cells, T and NK neutrophils, mast cells, microparticles (MPs), and platelets, as well as the dynamic changes in cell percentage and cell subtype heterogeneity. Results: Intratumoral injection of chemotherapy drug plus hapten induces an acute immune response in precancerous cervical lesions with HPV and further awakens immune cells to prevent the abnormal proliferation of the precancerous cells. Conclusion: HEIC provides a potential treatment method for cervical cancer and HPV infection tailored to each patient’s condition. [ABSTRACT FROM AUTHOR]

Context. Meat quality is increasingly being paid more attention by customers and enterprises. However, the modern pursuit of pork production has led to a decline in pork quality. Muscle fibre type is one of the important factors affecting meat quality that can be used as a key control point. Aims. This study set out to assess the effects of dietary guanidinoacetic acid (GAA) on the growth performance, meat quality, postmortem energy metabolism, and muscle fibre types of finishing pigs. Methods. In total, 180 healthy Duroc × Landrace × Meishan cross castrated male pigs with the similar weight (average 90 kg) were randomly divided into three treatments, with five replicates (pens) per treatment and 12 pigs per pen, including a GAA-free basal diet and basal diet with 0.05% or 0.10% GAA for 15 days. Key results. In longissimus thoracis muscle, the results indicated that GAA supplementation decreased the drip loss and the cooking loss in 0.10% GAA group. Meanwhile, in semitendinosus muscle, 0.10% GAA addition increased pH45 min, and decreased the cooking loss. Additionally, GAA addition increased the content of ATP and AMP in semitendinosus muscle. The mRNA expressions of MyHC-I and MyHC-IIa were increased, whereas MyHC-IIx and MyHC-IIb were decreased. Moreover, in longissimus thoracis muscle, GAA addition promoted the mRNA expressions of CaM and NFATc1; in semitendinosus muscle, dietary GAA up-regulated the CnA and NFATc1 mRNA expressions. Conclusions. GAA addition improved the meat quality, enhanced postmortem energy metabolism and promoted the conversion of fast-muscle fibre to slow-muscle fibre via activating the CaN/NFAT signalling. Implications. The addition of GAA can improve the meat quality of post-slaughter finishing pigs and provide a theoretical basis for the application of GAA in livestock production. [ABSTRACT FROM AUTHOR]

Water scarcity threatens agriculture in California. During the last two decades, historically severe droughts have led to severe water shortages. Under projected changes in climate, droughts of greater severity and duration will exacerbate this situation. California produces 80% of the world's almonds, which require consistent water supplies for irrigation. Almonds are the most commonly grown crop in California, covering nearly 1.4 million acres over about 8,000 farms. In response to these challenges, almond growers are considering a myriad of management strategies to save water and mitigate climate change. The Tree-Crop Remote Sensing of Evapotranspiration Experiment (T-REX) aims to identify water and orchard management opportunities to maximize water use efficiency and carbon sequestration in almonds and other woody perennial tree crops. The project combines satellite, uncrewed aerial vehicles, and proximal sensing technologies to retrieve key variables used to model surface fluxes and biophysical properties. We aim to advance our understanding of water management and cultural practices on water-carbon relationships in tree-perennial agroecosystems. Through new methods, such as evapotranspiration-based irrigation scheduling, even a modest 10% decrease in almond orchard irrigation across the state equates to about a third of the water in Lake Oroville, California's second-largest reservoir, at average levels. From a carbon perspective, almond orchards could sequester 8% of the state's current greenhouse gas emissions by transitioning toward climate-smart practices. As such, the almond industry is uniquely positioned to curb water use and contribute to climate change mitigation while maintaining economic viability of almond production. An overview of initial results related to evapotranspiration observational and modeling uncertainty and carbon sequestration potential are presented in this article. [ABSTRACT FROM AUTHOR]

In brief: Oocyte vitrification leads to DNA hypomethylation, which results in defect in early embryo development. This study reveals that oocyte vitrification impairs the DNA methylation pattern by influencing protein O-GlcNAcylation. Oocyte vitrification leads to decreased DNA methylation levels, which impairs the quality and the developmental potential of oocytes. However, the underlying molecular mechanism still need to be further revealed. In this study, mouse metaphase II (M II) oocytes were frozen by vitrification technology, while fresh oocytes were used as the control group. The effect of oocyte vitrification on protein O-GlcNAcylation and its impact on the developmental potential of oocytes were elucidated. We found that the protein O-GlcNAcylation levels were significantly increased in vitrified oocytes. Increase of protein O-GlcNAcylation levels in control oocytes by PUGNAc (an O-GlcNAcase inhibitor) decreases blastocyst rate after parthenogenetic activation (20.82% in PUGNAc-treated group; 53.82% in control group, P < 0.05). We also discovered that DNA methylation was disrupted in two-cell embryos derived from vitrified oocytes, resulting in decreased 5mC and increased 5hmC, showing similar phenotypes to that derived from PUGNActreated oocytes. In vitrified and PUGNAc-treated oocytes, O-GlcNAcylated TET3 was significantly increased. Notably, by inhibiting protein O-GlcNAcylation in vitrified oocytes using OSMI1 (an O-GlcNAc transferase inhibitor) we restored the DNA methylation in two-cell embryos and ameliorated the developmental defects in early embryo. Thus, elevated protein O-GlcNAcylation in vitrified oocytes is an essential contributor to their declining embryonic developmental potential. Modulation of protein O-GlcNAcylation improves the developmental potential of vitrified oocytes. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease characterized by extracellular senile plaques including amyloid-β peptides and intracellular neurofibrillary tangles consisting of abnormal Tau. Depression is one of the most common neuropsychiatric symptoms in AD, and clinical evidence demonstrates that depressive symptoms accelerate the cognitive deficit of AD patients. However, the underlying molecular mechanisms of depressive symptoms present in the process of AD remain unclear. Methods: Depressive-like behaviors and cognitive decline in hTau mice were induced by chronic restraint stress (CRS). Computational prediction and molecular experiments supported that an asparagine endopeptidase (AEP)- derived Tau fragment, Tau N368 interacts with peroxisome proliferator-activated receptor delta (PPAR-δ). Further behavioral studies investigated the role of Tau N368-PPAR-δ interaction in depressive-like behaviors and cognitive declines of AD models exposed to CRS. Results: We found that mitochondrial dysfunction was positively associated with depressive-like behaviors and cognitive deficits in hTau mice. Chronic stress increased Tau N368 and promoted the interaction of Tau N368 with PPAR-δ, repressing PPAR-δ-mediated transactivation in the hippocampus of mice. Then we predicted and identified the binding sites of PPAR-δ. Finally, inhibition of AEP, clearance of Tau N368 and pharmacological activation of PPAR-δ effectively alleviated CRS-induced depressive-like behaviors and cognitive decline in mice. Conclusion: These results demonstrate that Tau N368 in the hippocampus impairs mitochondrial function by suppressing PPAR-δ, facilitating the occurrence of depressive-like behaviors and cognitive decline. Therefore, our findings may provide new mechanistic insight in the pathophysiology of depression-like phenotype in mouse models of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: The clinical manifestations of multiple myeloma (MM) and bone metastatic tumor are both systemic bone pain, which is difficult to distinguish from imaging manifestations, leading to misdiagnosis and missed diagnosis. Case summary: We reported a man with a unique case whose tumors were MM with bone metastatic tumor of clear cell renal cell carcinoma (CCRCC). Computed tomography (CT) showed multifocal osteolytic bone destruction, while magnetic resonance imaging (MRI) showed multifocal bone marrow infiltration with soft tissue mass. Pathology and immunohistochemistry established the diagnosis of the coexistence of myeloma with bone metastatic tumor of CCRCC in the spine. Immunotherapy and systemic chemotherapy were adopted in the clinic, and vertebral decompression was performed after anemia was corrected. This case with MM and bone metastatic tumor of CCRCC received radiotherapy and immunotherapy and acquired satisfying outcome after 1 year of follow-up. Conclusion: It is difficult to differentiate MM and bone metastatic tumor on imaging, especially when there are bone lesions at the same time, which is an easily missed diagnosis and needs to be comprehensively evaluated in combination with functional procedures, clinical laboratory tests, and histopathology. [ABSTRACT FROM AUTHOR]