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This review critically evaluates the substantial role of exercise in enhancing cancer prevention, treatment, and patient quality of life. It conclusively demonstrates that regular physical activity not only reduces cancer risk but also significantly mitigates side effects of cancer therapies. The key findings include notable improvements in fatigue management, reduction of cachexia symptoms, and enhancement of cognitive functions. Importantly, the review elucidates the profound impact of exercise on tumor behavior, modulation of immune responses, and optimization of metabolic pathways, advocating for the integration of exercise into standard oncological care protocols. This refined abstract encourages further exploration and application of exercise as a pivotal element of cancer management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Feng, Feng, Wan, Luo, Qu and Wang.)

Cophylogeny has been identified between gut bacteria and their animal host and is highly relevant to host health, but little research has extended to gut bacteriophages. Here we use bee model to investigate host specificity and cophylogeny in the "animal-gut bacteria-phage" tripartite system. Through metagenomic sequencing upon different bee species, the gut phageome revealed a more variable composition than the gut bacteriome. Nevertheless, the bacteriome and the phageome showed a significant association of their dissimilarity matrices, indicating a reciprocal interaction between the two kinds of communities. Most of the gut phages were host generalist at the viral cluster level but host specialist at the viral OTU level. While the dominant gut bacteria Gilliamella and Snodgrassella exhibited matched phylogeny with bee hosts, most of their phages showed a diminished level of cophylogeny. The evolutionary rates of the bee, the gut bacteria and the gut phages showed a remarkably increasing trend, including synonymous and non-synonymous substitution and gene content variation. For all of the three codiversified tripartite members, however, their genes under positive selection and genes involving gain/loss during evolution simultaneously enriched the functions into metabolism of nutrients, therefore highlighting the tripartite coevolution that results in an enhanced ecological fitness for the whole holobiont., (© 2024. The Author(s).)

Developing a microenvironment-responsive drug delivery system (DDS) for the gastrointestinal system is of great interest to enhance drug efficiency and minimize side effects. Unfortunately, the rapid-flowing digestive juice in the gastrointestinal tract and the continuous contraction and peristalsis of the gastrointestinal tract muscle accelerate the elimination of drug carriers. In this study, a boric hydroxyl-modified mesoporous Mg(OH) 2 drug carrier is prepared to prolong the drug retention time. Results show that the newly designed DDS presents high biocompatibility and can immediately turn the free polyhydric alcohol molecules into a gelation form. The in situ-formed gelation network presents high viscosity and can prevent the drug carriers from being washed away by the digestive juice in the gastrointestinal tract.

The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is a critical clinical issue. Although previous studies have suggested macrophages as a key player in promoting inflammation and fibrosis during this transition, the heterogeneity and dynamic characterization of macrophages are still poorly understood. Here, we used integrated single-cell RNA sequencing and spatial transcriptomic to characterize the spatiotemporal heterogeneity of macrophages in murine AKI-to-CKD model of unilateral ischemia-reperfusion injury. A marked increase in macrophage infiltration at day 1 was followed by a second peak at day 14 post AKI. Spatiotemporal profiling revealed that injured tubules and macrophages co-localized early after AKI, whereas in late chronic stages had spatial proximity to fibroblasts. Further pseudotime analysis revealed two distinct lineages of macrophages in this transition: renal resident macrophages differentiated into the pro-repair subsets, whereas infiltrating monocyte-derived macrophages contributed to chronic inflammation and fibrosis. A novel macrophage subset, extracellular matrix remodeling-associated macrophages (EAMs) originating from monocytes, linked to renal fibrogenesis and communicated with fibroblasts via insulin-like growth factors (IGF) signalling. In sum, our study identified the spatiotemporal dynamics of macrophage heterogeneity with a unique subset of EAMs in AKI-to-CKD transition, which could be a potential therapeutic target for preventing CKD development., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Introduction: Increasing evidence indicates that microRNAs (miRNAs) play a crucial role in modulating tumor growth. This study is centered on investigating the contribution of miR-25 to the progression of Renal Cell Carcinoma (RCC)., Methods: The investigators examined the expression levels of miR-25 and ADAMTS16 in RCC samples and cell lines. The association between miR-25 and ADAMTS16 was validated via a luciferase reporter assay. Cell viability, apoptosis, migration, and invasion were evaluated utilizing CCK-8 and flow cytometry techniques, while the expression levels of ADAMTS16, β-catenin, GSK-3β, and p-GSK-3β were assessed through western blot analysis., Results: The investigation revealed elevated expression levels of miR-25 in RCC tissues. Subsequently, ADAMTS16 was identified as a target of miR-25. Increased miR-25 levels were associated with decreased expression of ADAMTS16, resulting in enhanced cell viability and diminished apoptosis. Conversely, inhibition of miR-25 led to decreased cell viability, proliferation, and migration. Additionally, the researchers observed that miR-25 triggered the phosphorylation of GSK-3β and β-catenin while leaving the total GSK-3β level unaffected., Conclusion: This study suggests that miR-25 regulates the expression of ADAMTS16 through the Wnt/β-catenin signaling pathway, providing new insights into the cause and potential treatment of RCC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

To support a phase 1 trial in patients with lymphomas, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for tazemetostat quantitation in 20 μL of human plasma. After protein precipitation, chromatographic separation employed a Kinetex C18 column and a gradient of 0.1% formic acid in both water and acetonitrile, during a 3-min run time. Detection was achieved using a SCIEX 6500+ tandem mass spectrometer with electrospray positive-mode ionization. Validation was based on the latest Food and Drug Administration guidance. With a stable isotopic internal standard, the assay was linear within the range of 10-5000 ng/mL and proved to be accurate (91.9%-103.7%) and precise (<4.4% imprecision). Recovery varied between 93.3% and 121.1%, and matrix effect ranged from -25.5% to -4.9%. Hemolysis, lipemia, and dilution did not impact quantitation. Plasma stability was confirmed after three freeze-thaw cycles, 24 h at room temperature, and 4 months at -80°C. Incurred sample reanalysis yielded 94.4% samples within 20% difference (n = 36). External validation showed a mean bias of -11.1%. Pharmacokinetic (PK) data obtained from three patients suggested variable concentration time profiles, warranting collection of further data. The assay proved to be suitable for tazemetostat quantitation in human plasma and will support clinical studies by defining tazemetostat PKs., (© 2024 John Wiley & Sons Ltd.)

Retinoic acid receptor responder protein-1 (RARRES1) is a podocyte-enriched transmembrane protein whose increased expression correlates with human glomerular disease progression. RARRES1 promotes podocytopenia and glomerulosclerosis via p53-mediated podocyte apoptosis. Importantly, the cytopathic actions of RARRES1 are entirely dependent on its proteolytic cleavage into a soluble protein (sRARRES1) and subsequent podocyte uptake by endocytosis, as a cleavage mutant RARRES1 exerted no effects in vitro or in vivo. As RARRES1 expression is upregulated in human glomerular diseases, here we investigated the functional consequence of podocyte-specific overexpression of RARRES1 in mice in the experimental focal segmental glomerulosclerosis and diabetic kidney disease. We also examined the effects of long-term RARRES1 overexpression on slowly developing aging-induced kidney injury. As anticipated, the induction of podocyte overexpression of RARRES1 (Pod-RARRES1 WT ) significantly worsened glomerular injuries and worsened kidney function in all three models, while overexpression of RARRES1 cleavage mutant (Pod-RARRES1 MT ) did not. Remarkably, direct uptake of sRARRES1 was also seen in proximal tubules of injured Pod-RARRES1 WT mice and associated with exacerbated tubular injuries, vacuolation, and lipid accumulation. Single-cell RNA sequence analysis of mouse kidneys demonstrated RARRES1 led to a marked deregulation of lipid metabolism in proximal tubule subsets. We further identified matrix metalloproteinase 23 (MMP23) as a highly podocyte-specific metalloproteinase and responsible for RARRES1 cleavage in disease settings, as adeno-associated virus 9-mediated knockdown of MMP23 abrogated sRARRES1 uptake in tubular cells in vivo. Thus, our study delineates a previously unrecognized mechanism by which a podocyte-derived protein directly facilitates podocyte and tubular injury in glomerular diseases and suggests that podocyte-specific functions of RARRES1 and MMP23 may be targeted to ameliorate glomerular disease progression in vivo., (Copyright © 2024 International Society of Nephrology. All rights reserved.)

This work utilizes defect engineering, heterostructure, pyridine N-doping, and carbon supporting to enhance cobalt-nickel selenide microspheres' performance in the oxygen electrode reaction. Specifically, microspheres mainly composed of CoNiSe 2 and Co 9 Se 8 heterojunction rich in selenium vacancies (V Se· ) wrapped with nitrogen-doped carbon nanotubes (p-CoNiSe/NCNT@CC) are prepared by Ar/NH 3 radio frequency plasma etching technique. The synthesized p-CoNiSe/NCNT@CC shows high oxygen reduction reaction (ORR) performance (half-wave potential (E 1/2 ) = 0.878 V and limiting current density (J L ) = 21.88 mA cm -2 ). The J L exceeds the 20 wt% Pt/C (19.34 mA cm -2 ) and the E 1/2 is close to the 20 wt% Pt/C (0.881 V). It also possesses excellent oxygen evolution reaction (OER) performance (overpotential of 324 mV@10 mA cm -2 ), which even exceeds that of the commercial RuO 2 (427 mV@10 mA cm -2 ). The density functional theory calculation indicates that the enhancement of ORR performance is attributed to the synergistic effect of plasma-induced V Se· and the CoNiSe 2 -Co 9 Se 8 heterojunction. The p-CoNiSe/NCNT@CC electrode assembled Zinc-air batteries (ZABs) show a peak power density of 138.29 mW cm -2 , outperforming the 20 wt% Pt/C+RuO 2 (73.9 mW cm -2 ) and other recently reported catalysts. Furthermore, all-solid-state ZAB delivers a high peak power density of 64.83 mW cm -2 and ultra-robust cycling stability even under bending., (© 2024 Wiley‐VCH GmbH.)

Label-free photoelectrochemical sensors have the advantages of high sensitivity and a simple electrode structure. However, its performance is greatly limited due to the photoactive materials' weak photoactivity and poor stability. Herein, a robust homogeneous photoelectrochemical (PEC) aptasensor has been constructed for atrazine (ATZ) based on photoetching (PE) surface oxygen vacancies (O v )-enriched Bismuth vanadate (BiVO 4 ) (PE-BVO). The surface of the O v improves the carrier separation ability of BiVO 4 , thus providing a superior signal substrate for the sensor. A thiol molecular layer self-assembled on PE-BVO acts as a blocker, while 2D graphene acts as a signal-on probe after release from the aptamer-graphene complex. The fabricated sensor has a wide linear detection range of 0.5 pM to 10.0 nM and a low detection limit of 0.34 pM (S/N = 3) for ATZ. In addition, it can efficiently work in a wide pH range (3-13) and high ionic strength (∼6 M Na + ), which provides promising opportunities for detecting environmental pollutants under complex conditions.

Herpes zoster (HZ) is rare in healthy children, but more prevalent in those with leukemia. Optimal timing of chemotherapy reinitiation after HZ treatment is challenging because chemotherapy suppresses immunity and increases risk of HZ relapse. We aimed to optimize the timing of chemotherapy reinitiation after HZ therapy in children with leukemia. The study included 31 children with acute leukemia and HZ infection. General information, clinical symptoms, laboratory test results, duration of HZ treatment, and prognosis were compared with those of children with leukemia alone. Correlation analysis was performed for 20 children who restarted chemotherapy after HZ treatment. Of 31 children with leukemia and HZ, 67.74% had lesions at multiple sites. The median time from chemotherapy initiation to HZ onset was 14.1 (1.5-29.5) months. Among 27 children included in the follow-up, there was one case of HZ relapse. After excluding children who did not continue chemotherapy after HZ treatment, the median interval between completion of HZ therapy and chemotherapy reinitiation in the remaining 20 children was 8.00 (- 3 to 27) days. Lymphocyte counts (LY#) on restarting chemotherapy correlated inversely with HZ lesion healing time (p < 0.05). LY# at the time of HZ onset were lower than those pre- and post-onset, and lower than those in the control group (p < 0.05). In conclusion, children with leukemia have a good HZ prognosis, but an increased risk of HZ recurrence. LY# at the time of chemotherapy reinitiation may be a useful indicator for selecting the optimal interval between antiviral therapy completion and chemotherapy reinitiation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Bivalent RSV prefusion F subunit vaccine (RSVpreF), comprised of equal quantities of stabilized prefusion F antigens from the major circulating subgroups (RSV A, RSV B), is licensed for prevention of RSV-associated lower respiratory tract illness (LRTI) in older adults and for maternal vaccination for prevention of RSV-associated LRTI in infants. To support licensure and large-scale manufacturing, this lot consistency study was conducted to demonstrate equivalence in immunogenicity across 3 RSVpreF lots., Methods: This phase 3, multicenter, parallel-group, placebo-controlled, randomized (1:1:1:1), double-blind study evaluated immunogenicity, safety, and tolerability of RSVpreF in healthy 18-49-year-old adults. Participants received a single 120-µg injection of 1 of 3RSVpreF lots or placebo. Geometric mean ratio (GMR) of RSV serum 50 % neutralizing geometric mean titers obtained 1 month after vaccination were compared between each vaccine lot for RSV A and RSV B, separately. Equivalence between lots was defined using a 1.5-fold criterion (GMR 95 % CIs for every lot pair within the 0.667-1.5 interval). Safety and tolerability were assessed., Results: Of 992participants vaccinated, 948 were included in the evaluable immunogenicity population. All 3 RSVpreF lots elicited strong immune responses, meeting the 1.5-fold equivalence criterion for all between-lot comparisons for both RSV A and RSV B. Across the 3 lots, RSV A and RSV B 50 % neutralizing geometric mean titers substantially increased from baseline (RSV A, 1671-1795; RSV B 1358-1429) to 1 month after RSVpreF vaccination (RSV A, 24,131-25,238; RSV B, 19,238-21,702), corresponding to ≥14-fold increases in 50 % neutralizing titers for both RSV A and RSV B from before to 1 month after vaccination. Single doses of RSVpreF were safe and well tolerated, with similar safety profiles across the 3 RSVpreF lots., Conclusions: These findings support the reproducibility of RSVpreF vaccine manufacturing with similar safety and reactogenicity profiles (NCT05096208)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jeffrey Baker received funding from Pfizer as an investigator for this study. Negar Aliabadi, Iona Munjal, Qin Jiang, Ye Feng, Linda G. Brock, David Cooper, Annaliesa S. Anderson, Kena A. Swanson, William C. Gruber, and Alejandra Gurtman received salary from their employment at Pfizer Inc and may hold Pfizer stock or stock options. Negar Aliabadi reports a relationship with Pfizer that includes: equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Iona Munjal reports financial support was provided by Pfizer. Iona Munjal reports a relationship with Pfizer Inc that includes: employment and equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Qin Jiang reports financial support was provided by Pfizer Inc. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ye Feng declares that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. David Cooper reports a relationship with Pfizer Inc that includes: employment and equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Annaliesa S. Anderson reports a relationship with Pfizer Inc that includes: employment and equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Kena A. Swanson reports writing assistance was provided by ICON. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. William C. Gruber reports financial support was provided by Pfizer Inc. William C. Gruber reports a relationship with Pfizer Inc that includes: employment and equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Alejandra Gurtman reports financial support was provided by Pfizer Inc. Alejandra Gurtman reports a relationship with Pfizer Inc that includes: employment and equity or stocks. I am a Pfizer employee. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier India Pvt Ltd. All rights reserved.)

Purpose: Aromatase inhibitor (AI) therapy reduces risk of recurrence and death for postmenopausal women with breast cancer (BC); however, AI-induced arthralgia (AIIA) can lead to discontinuation of treatment. Curcumin, a bioactive polyphenolic substance, may help ameliorate inflammation-related conditions including osteoarthritis and pain., Methods: We conducted a multisite randomized placebo-controlled, double-blind pilot trial (Alliance A22&#95;Pilot9) to evaluate the effects of nanoemulsion curcumin (NEC, 200 mg/day) in postmenopausal women experiencing AIIA for ≥ 3 months. The primary objective was to determine the feasibility of using Functional Assessment of Cancer Treatment-Endocrine Symptoms (FACT-ES) to detect changes from 0 (T0) to 3 months (T3) of NEC treatment in AI-induced symptoms and well-being; secondary objectives included evaluation of changes in Disabilities of the Shoulder, Arm, and Hand (DASH), Brief Pain Inventory-short form (BPI-SF), grip strength, and biomarkers at T0 and T3., Results: Forty-two patients were randomized to NEC or placebo; 34 women completed the 3-month study. Patient-reported outcome measures (PROMs: FACT-ES, DASH, BPI-SF) and biospecimens were collected at T0-T3 in > 80% of participants. Adherence was ≥ 90% for both arms. PROMs and grip strength did not differ significantly by treatment arm. Plasma curcumin was detected only in NEC arm participants. Serum estradiol and estrone levels were below detection or low on study agent. Gastrointestinal adverse effects were commonly reported in both arms., Conclusion: NEC versus placebo in a multisite randomized trial is feasible and well-tolerated. Additional studies with larger sample size are needed to further evaluate the efficacy and safety of NEC in treatment of AIIA., Clinicaltrials: gov Identifier: NCT03865992, first posted March 7, 2019., (© 2024. The Author(s).)

Objective: The United States (U.S.) and Mexico have vastly different lifetime prevalence of posttraumatic stress disorder (PTSD), despite similarly high rates of trauma exposure. To explain this disparate prevalence, we created the Perception of Trauma Difficulty Assessment Tool (PTDAT) to identify four social comparison effect types that inform perception of trauma difficulty (i.e., Upward Assimilation Effect, Downward Assimilation Effect, Downward Contrast Effect, Upward Contrast Effect) to determine whether there was a dominant effect type associated with respondents' perception of coping with trauma difficulty for a sample of U.S. Americans and Mexicans. We identified sociodemographic characteristics and the degree of trauma exposure that associated with PTSD, PTSD symptom severity, and functional impairment for each effect type., Method: This was a cross-sectional study of a sample of 898 U.S. Americans and 902 Mexicans. A chi-square test determined whether there was a dominant effect type for each national group. For each effect type, multiple regression analyses identified predictors of PTSD, PTSD symptom severity, and functional impairment., Results: For U.S. Americans, trauma exposure was a predictor for PTSD for effect type Upward Contrast Effect, when respondents contrasted from an excellent appraisal of most people by making a poor self-appraisal. For Mexicans, all effect types had predictors for PTSD, with trauma exposure being a predictor for all., Conclusions: These preliminary findings provide support to consider patients' social context as it informs their perception of their capacity to cope, which may maintain PTSD. Future research is needed to determine whether perceptions of trauma difficulty are stable over time. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

We report the findings of a multi-language and multi-lab investigation of young infants' ability to discriminate lexical tones as a function of their native language, age and language experience, as well as of tone properties. Given the high prevalence of lexical tones across human languages, understanding lexical tone acquisition is fundamental for comprehensive theories of language learning. While there are some similarities between the developmental course of lexical tone perception and that of vowels and consonants, findings for lexical tones tend to vary greatly across different laboratories. To reconcile these differences and to assess the developmental trajectory of native and non-native perception of tone contrasts, this study employed a single experimental paradigm with the same two pairs of Cantonese tone contrasts (perceptually similar vs. distinct) across 13 laboratories in Asia-Pacific, Europe and North-America testing 5-, 10- and 17-month-old monolingual (tone, pitch-accent, non-tone) and bilingual (tone/non-tone, non-tone/non-tone) infants. Across the age range and language backgrounds, infants who were not exposed to Cantonese showed robust discrimination of the two non-native lexical tone contrasts. Contrary to this overall finding, the statistical model assessing native discrimination by Cantonese-learning infants failed to yield significant effects. These findings indicate that lexical tone sensitivity is maintained from 5 to 17 months in infants acquiring tone and non-tone languages, challenging the generalisability of the existing theoretical accounts of perceptual narrowing in the first months of life. RESEARCH HIGHLIGHTS: This is a multi-language and multi-lab investigation of young infants' ability to discriminate lexical tones. This study included data from 13 laboratories testing 5-, 10-, and 17-month-old monolingual (tone, pitch-accent, non-tone) and bilingual (tone/non-tone, non-tone/non-tone) infants. Overall, infants discriminated a perceptually similar and a distinct non-native tone contrast, although there was no evidence of a native tone-language advantage in discrimination. These results demonstrate maintenance of tone discrimination throughout development., (© 2023 John Wiley & Sons Ltd.)

Pathogenic bacteria significantly contribute to elevated morbidity and mortality rates, highlighting the urgent need for early and precise detection. Currently, there is a paucity of effective broad-spectrum methods for detecting pathogenic bacteria. We have developed an innovative proton-responsive series piezoelectric quartz crystal (PR-SPQC) platform for the broad-spectrum identification of pathogenic bacteria. This was achieved by retrieving and aligning sequences from the NCBI GenBank database to identify and validate 16S rRNA oligonucleotide sequences that are signatures of pathogenic bacteria but absent in humans or fungi. The hyperbranched rolling circle amplification, activated exclusively by the screened target, exponentially generates protons that are detected by SPQC through a 2D polyaniline (PANI) film. The PR-SPQC platform demonstrates broad-spectrum capabilities in detecting pathogenic bacteria, with a detection limit of 2 CFU/mL within 90 min. Clinical testing of blood samples yielded satisfactory results. With its advantages in miniaturization, cost efficiency, and suitability for point-of-care testing, PR-SPQC has the potential to be extensively used for the rapid identification of diverse pathogenic bacteria within clinical practice and public health sectors.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen that causes severe abortions in sows and high piglet mortality, resulting in huge economic losses to the pig industry worldwide. The emerging and novel PRRSV isolates are clinically and biologically important, as there are likely recombination and pathogenic differences among PRRSV genomes. Furthermore, the NADC34-like strain has become a major epidemic strain in some parts of China, but the characterization and pathogenicity of the latest strain in Inner Mongolia have not been reported in detail. In this study, an NADC34-like strain (CHNMGKL1-2304) from Tongliao City, Inner Mongolia was successfully isolated and characterized, and confirmed the pathogenicity in pigs. The phylogenetic tree showed that this strain belonged to sublineage 1.5 and had high homology with the strain JS2021NADC34. There is no recombination between CHNMGKL1-2304 and any other domestic strains. Animal experiments show that the CHNMGKL1-2304 strain is moderately virulent to piglets, which show persistent fever, weight loss and high morbidity but no mortality. The presence of PRRSV nucleic acids was detected in both blood, tissues, nasal and fecal swabs. In addition, obvious pathological changes and positive signals were observed in lung, lymph node, liver and spleen tissues when subjected to hematoxylin-eosin (HE) staining and immunohistochemistry (IHC). This report can provide a basis for epidemiological investigations and subsequent studies of PRRSV.

Background: Cold stress has negative effects on the growth and health of mammals, and has become a factor restricting livestock development at high latitudes and on plateaus. The gut-liver axis is central to energy metabolism, and the mechanisms by which it regulates host energy metabolism at cold temperatures have rarely been illustrated. In this study, we evaluated the status of glycolipid metabolism and oxidative stress in pigs based on the gut-liver axis and propose that AMP-activated protein kinase (AMPK) is a key target for alleviating energy stress at cold temperatures by dietary fat supplementation., Results: Dietary fat supplementation alleviated the negative effects of cold temperatures on growth performance and digestive enzymes, while hormonal homeostasis was also restored. Moreover, cold temperature exposure increased glucose transport in the jejunum. In contrast, we observed abnormalities in lipid metabolism, which was characterized by the accumulation of bile acids in the ileum and plasma. In addition, the results of the ileal metabolomic analysis were consistent with the energy metabolism measurements in the jejunum, and dietary fat supplementation increased the activity of the mitochondrial respiratory chain and lipid metabolism. As the central nexus of energy metabolism, the state of glycolipid metabolism and oxidative stress in the liver are inconsistent with that in the small intestine. Specifically, we found that cold temperature exposure increased glucose transport in the liver, which fully validates the idea that hormones can act on the liver to regulate glucose output. Additionally, dietary fat supplementation inhibited glucose transport and glycolysis, but increased gluconeogenesis, bile acid cycling, and lipid metabolism. Sustained activation of AMPK, which an energy receptor and regulator, leads to oxidative stress and apoptosis in the liver; dietary fat supplementation alleviates energy stress by reducing AMPK phosphorylation., Conclusions: Cold stress reduced the growth performance and aggravated glycolipid metabolism disorders and oxidative stress damage in pigs. Dietary fat supplementation improved growth performance and alleviated cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis. In this study, we highlight the importance of AMPK in dietary fat supplementation-mediated alleviation of host energy stress in response to environmental changes., (© 2024. The Author(s).)

Introduction: Rare myocarditis and pericarditis cases have occurred in coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine recipients. Troponin levels, a potential marker of myocardial injury, were assessed in healthy participants before and after BNT162b2 vaccination., Methods: Vaccine-experienced 12- to 30-year-olds in phase 3 crossover C4591031 Substudy B (NCT04955626) who had two or three prior BNT162b2 30-μg doses were randomized to receive BNT162b2 30 μg followed by placebo, or placebo followed by BNT162b2 30 µg, 1 month apart. A participant subset, previously unvaccinated against COVID-19, in the phase 3 C4591007 study (NCT04816643) received up to three vaccinations (BNT162b2 10 μg or placebo [5- to 11-year-olds]) or open-label BNT162b2 30 μg (12- to 15-year-olds). Blood samples collected pre-vaccination, 4 days post-vaccination, and 1-month post-vaccination (C4591031 Substudy B only) were analyzed. Frequencies of elevated troponin I levels (male, > 35 ng/l; female, > 17 ng/l) were assessed., Results: Percentages of 12- to 30-year-olds (n = 1485) in C4591031 Substudy B with elevated troponin levels following BNT162b2 or placebo receipt were 0.5% and 0.8% before vaccination, 0.7% and 1.0% at day 4, and 0.7% and 0.5% at 1 month, respectively. In Study C4591007 (n = 1265), elevated troponin I levels were observed in 0.2, 0.4, and 0.2% of 5- to 11-year-old BNT162b2 recipients at baseline and 4 days post-dose 2 and 3, respectively; corresponding values in 12- to 15-year-olds were 0.4, 0.4, and 0.7%. No 5- to 11-year-old placebo recipients had elevated troponin levels. No myocarditis or pericarditis cases or deaths were reported., Conclusions: Among 5- to  < 30-year-olds in both studies, troponin levels were rarely elevated (≤ 1.0%) and similar before and post-vaccination; troponin levels were also similar between BNT162b2 and placebo in 12- to 30-year-old and 5- to 11-year-old recipients in the respective studies. No myocarditis or pericarditis cases were reported. These findings did not provide evidence that BNT162b2 causes troponin elevations. No utility of routine measurement of troponin levels in asymptomatic BNT162b2 recipients was identified., (© 2024. Pfizer Inc.)

HIPK2 is a multifunctional kinase that acts as a key pathogenic mediator of chronic kidney disease and fibrosis. It acts as a central effector of multiple signaling pathways implicated in kidney injury, such as TGF-β/Smad3-mediated extracellular matrix accumulation, NF-κB-mediated inflammation, and p53-mediated apoptosis. Thus, a better understanding of the specific HIPK2 regions necessary for distinct downstream pathway activation is critical for optimal drug development for CKD. Our study now shows that caspase-6-mediated removal of the C-terminal region of HIPK2 (HIPK2-CT) lead to hyperactive p65 NF-κB transcriptional response in kidney cells. In contrast, the expression of cleaved HIPK2-CT fragment could restrain the NF-κB transcriptional activity by cytoplasmic sequestration of p65 and the attenuation of IκBα degradation. Therefore, we examined whether HIPK2-CT expression can be exploited to restrain renal inflammation in vivo. The induction of HIPK2-CT overexpression in kidney tubular cells attenuated p65 nuclear translocation, expression of inflammatory cytokines, and macrophage infiltration in the kidneys of mice with unilateral ureteral obstruction and LPS-induced acute kidney injury. Collectively, our findings indicate that the HIPK2-CT is involved in the regulation of nuclear NF-κB transcriptional activity and that HIPK2-CT or its analogs could be further exploited as potential antiinflammatory agents to treat kidney disease.

Objectives: To date, the majority of research on resting-state functional magnetic resonance imaging (rs-fMRI) in the developing brain has primarily centered on adolescents and adults, leaving a gap in understanding variations in spontaneous brain activity at rest in preterm infants. This study aimed to uncover and comprehend the distinctions in spontaneous brain activity between preterm and term infants, with the goal of establishing a foundation for assessing the condition of preterm infants., Methods: In this study, 14 term infants and 15 preterm infants with equivalent gestational age were carefully chosen from the neonatal unit of Anhui Provincial Children's Hospital. The amplitude of low-frequency fluctuations (ALFF) intensity was assessed using resting-state functional magnetic resonance imaging (rs-fMRI) to examine brain activity in both groups. Subsequently, the differences between the term and preterm infants were statistically analyzed using a two-sample t -test. A p- value of <0.05, corrected for the REST Gaussian Random Fields, was deemed to be statistically significant., Results: In comparison to the term infant group, the preterm infant group exhibited a significant increase in the ALFF value in the left precuneus, left frontal superior orbital gyrus, and left calcarine cortex., Conclusion: Significant variances in spontaneous brain activity have been observed in various regions between term infants and preterm infants of equivalent gestational age. These variations could potentially impact the emotional and cognitive development of preterm infants in the long term., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Feng, Wang, Li, Dai and Zhang.)

Objective: To explore the effects of budesonide combined with Bifidobacteria and Lactobacilli on the lung function and intestinal microbiota of patients with chronic obstructive pulmonary disease (COPD)., Methods: Clinical data of 124 COPD patients admitted to Fengcheng Hospital, Fengxian District, Shanghai from February 2021 to February 2023 were retrospectively analyzed. Patients either received budesonide treatment alone (n=59, control group) or budesonide combined with Bifidobacteria and Lactobacilli (n=65, observation group). Levels of lung function indicators, symptom relief time, gut microbiota levels, and quality of life were compared between the two groups before and after the treatment., Results: After two weeks of treatment, the improvement of lung function in the observation group was better than that in the control group ( P <0.05). Compared to budesonide treatment alone, combined budesonide, Bifidobacteria, and Lactobacilli treatment were associated with shorter symptom relief time ( P <0.05), and with more significant improvement of intestinal microbiota level ( P <0.05) and the quality of life ( P <0.05)., Conclusions: Budesonide combined with Bifidobacteria and Lactobacilli can effectively alleviate clinical symptoms, regulate intestinal microbiota, improve lung function and the quality of life of COPD patients., (Copyright: © Pakistan Journal of Medical Sciences.)

The adipose-derived stem cells (ASCs) are a valuable resource for regenerative medicine and essential materials for research in fat deposition. However, the isolation procedure of ASCs has not been standardized and needs to be harmonized; differences in proliferation and adipogenic differentiation of ASCs obtained from different fat depots have not been well characterized. In the present study, we compared the efficiency of ASCs isolation by enzymatic treatment and explant culture methods and the proliferation ability and adipogenic differentiation potential of ASCs isolated from subcutaneous and visceral fat depots. The explant culture method was simple and with no need for expensive enzymes while the enzymatic treatment method was complex, time consuming and costly. By the explant culture method, a larger number of ASCs were isolated from subcutaneous and visceral fat depots. By contrast, fewer ASCs were obtained by the enzymatic treatment method, especially from visceral adipose. ASCs isolated by the explant culture method performed well in cell proliferation and adipogenic differentiation, though they were slightly lower than those by the enzymatic treatment method. ASCs isolated from visceral depot demonstrated higher proliferation ability and adipogenic differentiation potential. In total, the explant culture method is simpler, more efficient, and lower cost than the enzymatic treatment method for ASCs isolation; compared with visceral adipose, subcutaneous adipose is easier to isolate ASCs; however, the visceral ASCs are superior to subcutaneous ASCs in proliferation and adipogenic differentiation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The global headlines have been dominated by the sudden and widespread outbreak of monkeypox, a rare and endemic zoonotic disease caused by the monkeypox virus (MPXV). Genomic composition based machine learning (ML) methods have recently shown promise in identifying host adaptability and evolutionary patterns of virus. Our study aimed to analyze the genomic characteristics and evolutionary patterns of MPXV using ML methods. Methods: The open reading frame (ORF) regions of full-length MPXV genomes were filtered and 165 ORFs were selected as clusters with the highest homology. Unsupervised machine learning methods of t-distributed stochastic neighbor embedding (t-SNE), Principal Component Analysis (PCA), and hierarchical clustering were performed to observe the DCR characteristics of the selected ORF clusters. Results: The results showed that MPXV sequences post-2022 showed an obvious linear adaptive evolution, indicating that it has become more adapted to the human host after accumulating mutations. For further accurate analysis, the ORF regions with larger variations were filtered out based on the ranking of homology difference to narrow down the key ORF clusters, which drew the same conclusion of linear adaptability. Then key differential protein structures were predicted by AlphaFold 2, which meant that difference in main domains might be one of the internal reasons for linear adaptive evolution. Discussion: Understanding the process of linear adaptation is critical in the constant evolutionary struggle between viruses and their hosts, playing a significant role in crafting effective measures to tackle viral diseases. Therefore, the present study provides valuable insights into the evolutionary patterns of the MPXV in 2022 from the perspective of genomic composition characteristics analysis through ML methods., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Li, Cai, Kang, Feng, Li, Chen, Li, Bao and Jiang.)

The pericarp of Herpetospermum pedunculosum (HPP) has traditionally been used for treating jaundice and hepatitis. However, the specific hepatoprotective components and their safety/efficacy profiles remain unclear. This study aimed to characterize the total cucurbitacins (TCs) extracted from HPP and evaluate their hepatoprotective potential. As a reference, Hu-lu-su-pian (HLSP), a known hepatoprotective drug containing cucurbitacins, was used for comparison of chemical composition, effects, and safety. Molecular networking based on UHPLC-MS/MS identified cucurbitacin B, isocucurbitacin B, and cucurbitacin E as the major components in TCs, comprising 70.3%, 26.1%, and 3.6% as determined by RP-HPLC, respectively. TCs treatment significantly reversed CCl 4 -induced metabolic changes associated with liver damage in a dose-dependent manner, impacting pathways including energy metabolism, oxidative stress and phenylalanine metabolism, and showed superior efficacy to HLSP. Safety evaluation also showed that TCs were safe, with higher LD 50 and no observable adverse effect level (NOAEL) values than HLSP. The median lethal dose (LD 50 ) and NOAEL values of TCs were 36.21 and 15 mg/kg body weight (BW), respectively, while the LD 50 of HLSP was 14 mg/kg BW. In summary, TCs extracted from HPP demonstrated promising potential as a natural hepatoprotective agent, warranting further investigation into synergistic effects of individual cucurbitacin components., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Xu, Hu, Meng, Zheng, Wu, Feng and Wang.)

Bats are associated with the circulation of most mammalian filoviruses (FiVs), with pathogenic ones frequently causing deadly hemorrhagic fevers in Africa. Divergent FiVs have been uncovered in Chinese bats, raising concerns about their threat to public health. Here, we describe a long-term surveillance to track bat FiVs at orchards, eventually resulting in the identification and isolation of a FiV, Dehong virus (DEHV), from Rousettus leschenaultii bats. DEHV has a typical filovirus-like morphology with a wide spectrum of cell tropism. Its entry into cells depends on the engagement of Niemann-Pick C1, and its replication is inhibited by remdesivir. DEHV has the largest genome size of filoviruses, with phylogenetic analysis placing it between the genera Dianlovirus and Orthomarburgvirus , suggesting its classification as the prototype of a new genus within the family Filoviridae . The continuous detection of viral RNA in the serological survey, together with the wide host distribution, has revealed that the region covering southern Yunnan, China, and bordering areas is a natural circulation sphere for bat FiVs. These emphasize the need for a better understanding of the pathogenicity and potential risk of FiVs in the region., Competing Interests: Competing interests statement:The authors declare no competing interest.

Rabies is a fatal zoonotic disease that poses a threat to public health. Rabies virus (RABV) is excreted in the saliva of infected animals, and is primarily transmitted by bite. The role of the salivary glands in virus propagation is significant, but has been less studied in the pathogenic mechanisms of RABV. To identify functionally important genes in the salivary glands, we used RNA sequencing (RNA-seq) to establish and analyze mRNA expression profiles in parotid tissue infected with two RABV strains, CVS-11 and PB4. The biological functions of differentially expressed genes (DEGs) were determined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which revealed 3,764 DEGs (678 up-regulated and 3,086 down-regulated) in the CVS-11 infected group and 4,557 DEGs (874 up-regulated and 3,683 down-regulated) in the PB4 infected group. Various biological processes are involved, including the salivary secretion pathway and the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway. This study provides the first mapping of the transcriptome changes in response to RABV infection in parotid tissue, offering new insights into the study of RABV-affected salivary gland function and RABV pathogenic mechanisms in parotid tissue. The salivary gland-enriched transcripts may be potential targets of interest for rabies disease control., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guo, Zhang, Feng, Liu, Wang, Zhang, Wang, Zhang and Guo.)

As important components of the mammalian diet and tissues, fats are involved in a variety of biological processes in addition to providing energy. In general, the increase in basal metabolism and health risks under cold temperature conditions causes the host to need more energy to maintain body temperature and normal biological processes. The intestine and its microbiota are key components in orchestrating host metabolic homeostasis and immunity, and respond rapidly to changing environmental conditions. However, the role of dietary-fat supplementation in regulating host homeostasis of metabolism and barrier functions through gut microbiota at cold temperatures is incompletely understood. Our results showed that dietary-fat supplementation alleviated the negative effects of cold temperatures on the alpha-diversity of both ileal and colonic microbiota. Cold temperatures altered the ileal and colonic microbiota of pigs, and the extent of changes was more pronounced in the colonic microbiota. Translocation of the gut microbiota was restored after supplementation with a high-fat diet. In addition, cold temperatures exacerbated ileal mucosal damage and inflammation, and disrupted barrier function, which may be associated with decreased concentrations of butyrate and isobutyrate. Cold temperature-induced metabolic dysbiosis was manifested by altered hormone levels and upregulation of expression of multiple metabolites involved in metabolism (lipids, amino acids and minerals) and the immune response. Supplementation with a high-fat diet restored metabolic homeostasis and barrier function by improving gut-microbiota composition and increasing SCFAs concentrations in pigs. In conclusion, cold temperatures induced severe translocation of microbiota and barrier damage. These actions increased the risk of metabolic imbalance. Dietary-fat supplementation alleviated the adverse effects of cold temperatures on host metabolism by remodeling the gut microbiota.

Circular RNAs (circRNA) are a kind of endogenous biological macromolecules that play significant roles in many biological processes, including adipogenesis, a precisely orchestrated process that is mediated by a large number of factors. Among them, peroxisome proliferator-activated receptor gamma (PPARG), is undoubtedly the most important regulator of adipocyte development in all types of adipose tissue. The formation of intramuscular fat (IMF), is a key factor that influences the meat quality in livestock animals. PPARG has been demonstrated to show a positive correlation with IMF deposition although the regulatory mechanism involved is not known. This study demonstrates that PPARG mediates IMF deposition by producing multiple exonic circRNAs (circPPARGs). Three circPPARGs promote adipogenic differentiation and inhibit the proliferation of intramuscular preadipocytes and these effects are conserved across several species including buffaloes, cattle and mice. Notably, circPPARG1 interacts with PPARG protein to inhibit the transcription of hormone sensitive lipase (HSL) involved in lipolysis. In addition, the positive effects of circPPARG1 on IMF deposition were identified in mice in vivo. Thus, PPARG drives IMF deposition, not only through the common transcription factor pathway, but also by producing circRNAs. This study provides new insights into our understanding of the regulatory mechanisms of PPARG in IMF deposition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Immune checkpoint inhibitor (ICI) rechallenge in non-small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD-1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Intramuscular fat (IMF) is a crucial determinant of meat quality and is influenced by various regulatory factors. Despite the growing recognition of the important role of long noncoding RNAs (lncRNAs) in IMF deposition, the mechanisms underlying buffalo IMF deposition remain poorly understood. In this study, we identified and characterized a lncRNA, lncFABP4, which is transcribed from the antisense strand of fatty acid-binding protein 4 (FABP4). lncFABP4 inhibited cell proliferation in buffalo intramuscular preadipocytes. Moreover, lncFABP4 significantly increased intramuscular preadipocyte differentiation, as indicated by an increase in the expression of the adipogenic markers peroxisome proliferator-activated receptor gamma (PPARG), CCAAT enhancer binding protein alpha (C/EBPα), and FABP4. Mechanistically, lncFABP4 was found to have the potential to regulate downstream gene expression by participating in protein-protein interaction pathways. These findings contribute to further understanding of the intricate mechanisms through which lncRNAs modulate intramuscular adipogenesis in buffaloes., (© 2024 Japanese Society of Animal Science.)

Objective: Erxian Decoction (EXD) is traditionally employed in the treatment of menopausal syndromes, although its underlying mechanisms remain largely undefined. Given that the senescence of bone marrow mesenchymal stem cells (BMSCs) is intertwined with organismal aging and associated diseases, this study endeavored to elucidate the influence of EXD on aging BMSCs and uncover the mechanisms through which EXD impedes BMSC senescence., Methods: Initially, we probed the anti-senescent mechanisms of EXD on BMSCs via network pharmacology. We subsequently isolated and identified exosomes from the serum of EXD-fed rats (EXD-Exos) and administered these to H 2 O 2 -induced aging BMSC. Assays were conducted to assess BMSC senescence indicators and markers pertinent to mitochondrial autophagy. Treatments with mitophagy inhibitors and activators were then employed to substantiate our findings., Results: Protein-protein interaction (PPI) network analyses spotlighted AKT1, TP53, TNF, JUN, VEGFA, IL6, CASP3 and EGFR as focal targets. Gene Ontology and Kyoto Encylcopedia of Genes and Genomes pathway analyses underscored oxidative stress, mitophagy and cell proliferation as pivotal processes. Our cellular assays ascertained that EXD-Exos mitigated H 2 O 2 -induced senescence phenotypes in BMSCs. Moreover, EXD-Exos ameliorated disrupted mitophagy in BMSCs, as evidenced by enhanced cellular membrane potential and diminished reactive oxygen species levels. Intriguingly, EXD-Exos also preserved the osteogenic differentiation potential of BMSCs while curtailing their adipogenic propensity., Conclusion: Our findings compellingly suggest that EXD counteracts BMSC senescence by fostering mitophagy., (© 2023 John Wiley & Sons Ltd.)

We have developed and validated a novel LC-MS/MS method for the simultaneous quantification of ZEN-3694 and its active metabolite ZEN-3791 in human plasma after protein precipitation. Stable isotope-labeled versions were used as internal standards. Chromatographic separation was achieved on a Kinetex C18 column using 0.1% formic acid in H 2 O and 0.1% formic acid in MeOH as mobile phases. Detection was performed via positive electrospray ionization mode with multiple reaction monitoring. The assay exhibited linearity in the concentration range of 5-5000 ng/ml for both analytes. Intra- and inter-assay precision and accuracy were within ±11%. ZEN-3694 and ZEN-3791 recoveries were between 93 and 105%. This LC-MS/MS assay is an essential tool to study ZEN-3694 in an ongoing clinical trial (NCT04840589).

Sulfation and desulfation of steroids are opposing processes that regulate the activation, metabolism, excretion, and storage of steroids, which account for steroid homeostasis. Steroid sulfation and desulfation are catalyzed by cytosolic sulfotransferase and steroid sulfatase, respectively. By modifying and regulating steroids, cytosolic sulfotransferase (SULT) and steroid sulfatase (STS) are also involved in the pathophysiology of steroid-related diseases, such as hormonal dysregulation, metabolic disease, and cancer. The estrogen sulfotransferase (EST, or SULT1E1) is a typical member of the steroid SULTs. This review is aimed to summarize the roles of SULT1E1 and STS in steroid homeostasis and steroid-related diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Although nuts play an important role in preventing cardiovascular disease, the metabolic cues by which nuts regulate blood pressure have not been fully understood.Aims:We conducted a nested case-control study in a prospective cohort study of Southwest China children to explore the potential lipid metabolites related to the relationship between nut dietary and blood pressure., Methods: Forty-three hypertension cases and 53 controls serum samples were obtained for lipidomic data analysis using a liquid chromatography mass spectrometry platform., Results: We identified four lipid metabolites that are associated with nut intake by a generalized linear model and logistic regression analysis, including phosphatidylglycerol 43:6 [PG (43:6)], phosphatidylcholine 18:0/20:3 [PC (18:0/20:3)], and two phosphatidylethanolamine (PE) compounds [PE (P-16:0/20:4) and PE (P-22:0/18:2)]. Logistic regression analysis indicated that the levels of PG (43:6) and PE (P-16:0/20:4) were negatively associated with hypertension in children, which might be useful biomarkers for predicting childhood hypertension. Further mediation analysis revealed that PG (43:6) and PC (18:0/20:3) function as mediating variables between nut intake and blood pressure levels., Conclusion: This study provides scientific evidence that nut consumption induces some beneficial changes in lipid metabolism, which may reduce the risk of hypertension in children.

Background: Nuts and algae have been shown to improve BP levels, but their effectiveness is controversial., Aims: This study aims to illustrate the effect of dietary pattern with nuts and algae-less on BP levels in children and adolescents from a cross-sectional study., Methods: A total of 5645 children from the Chongqing Children's Health Cohort, aged 9.34 ± 1.74 years with 52.05% males, were analyzed. Stratified analysis was conducted to explore the differences between the two dietary patterns in urban or rural areas, as well as the differences in different gender. Logistic regression was used to analyze the influence factors of increased BP. And a GLM was used to analyze the influence of the two dietary patterns on systolic blood pressure (SBP, mmHg), diastolic blood pressure (DBP, mmHg), and mean arterial pressure (MAP, mmHg)., Results: Children with nuts and algae-less dietary patterns had higher SBP (104.68 ± 10.31 vs 103.81 ± 9.74, P = .006), DBP (64.27 ± 7.53 vs 63.55 ± 7.52, P = .002), and MAP (77.74 ± 7.75 vs 76.97 ± 7.52, P = .001) compared with those children with a balanced diet. After adjusting for covariates, the nuts and algae-less diet was a risk factor for hypertension in children when compared with the balanced diet(OR(95%CI):1.455(1.097,1.930), P = .009). The nuts and algae-less diet has a significant influence on SBP (104.68 ± 10.31 mmHg vs.103.81 ± 9.74 mmHg, P = .006). Stratified analysis by sex showed that nuts and algae-less dietary patterns had a more significant impact on females than males., Conclusion: Nuts and algae-less dietary pattern correlated with increased BP levels in children, and a greater impact on SBP levels was found in females, suggesting that a balanced diet with appropriate nuts and algae should be proposed for children in China.

This study investigated the nutritional benefits of complex dietary fiber (beta-glucan and fructo-oligosaccharides, CDF) supplementation in sows and piglets during late pregnancy and lactation. Twenty-four sows were randomly divided into two groups: the control group was fed a basal diet ( n = 12), and the experimental group was fed a CDF diet (0.25% CDF replaced the same proportion of corn in the basal diet, n = 12). Dietary treatment was given from day 107 of pregnancy to day 25 of lactation. The results of this experiment showed that CDF increased the average daily feed intake (ADFI) of sows during lactation and the weaning body weight (BW) and average daily gain of piglets. Dietary CDF supplementation improved the antioxidant capacity and immune level of sows and decreased the serum zonulin level. Dietary supplementation with CDF increased the levels of antioxidant activity, immunoglobulin, and anti-inflammatory factor interleukin-10 (IL-10) in milk. Meanwhile, piglets in the CDF group had increased serum antioxidant activity, immunoglobulin, and growth-related hormone levels; decreased malondialdehyde (MDA), interleukin-6 (IL-6), and D-lactic acid (D-LA) levels; and increased fecal short-chain fatty acid content. In addition, the CDF group increased the diversity of microorganisms in sow feces. In conclusion, the supplementation of a diet with CDF in late pregnancy and lactation can alleviate the oxidative stress of sows, improve milk quality, and have significant positive effects on the antioxidant capacity and growth performance of piglets.

Intramuscular fat (IMF) content is one of the most significant factors influencing beef quality in terms of tenderness, flavor, and juiciness. Thus, internal factors affecting IMF deposition have received considerable attention for decades. In this study, we demonstrated a long non-coding RNA, lnc210, promoted adipogenic differentiation of buffalo intramuscular adipocytes. lnc210 was rich in adipose tissue and showed increased expression with the adipogenic differentiation of buffalo intramuscular adipocytes. lnc210 was mainly expressed in the nucleus of adipocytes. Full-length lnc210 was obtained by rapid amplification of cDNA ends technology. lnc210 overexpression promoted lipid accumulation by upregulating the mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG) and CCAAT enhancer binding protein alpha (C/EBPα) in buffalo intramuscular adipocytes. These results provide a basis for an in-depth analysis of the role of lnc210 in accelerating IMF deposition in buffaloes.

The central nervous system is susceptible to the modulation of various neurophysiological processes by the cytochrome P450 enzyme (CYP), which plays a crucial role in the metabolism of neurosteroids. The antiepileptic drug phenytoin (PHT) has been observed to induce neuronal side effects in patients, which could be attributed to its induction of CYP expression and testosterone (TES) metabolism in the hippocampus. While pregnane X receptor (PXR) is widely known for its regulatory function of CYPs in the liver, we have discovered that the treatment of mice with pregnenolone 16α-carbonitrile (PCN), a PXR agonist, has differential effects on CYP expression in the liver and hippocampus. Specifically, the PCN treatment resulted in the induction of cytochrome P450, family 3, subfamily a, polypeptide 11 (CYP3A11), and CYP2B10 expression in the liver, while suppressing their expression in the hippocampus. Functionally, the PCN treatment protected mice from PHT-induced hippocampal nerve injury, which was accompanied by the inhibition of TES metabolism in the hippocampus. Mechanistically, we found that the inhibition of hippocampal CYP expression and attenuation of PHT-induced neurotoxicity by PCN were glucocorticoid receptor dependent, rather than PXR independent, as demonstrated by genetic and pharmacological models. In conclusion, our study provides evidence that PCN can negatively regulate hippocampal CYP expression and attenuate PHT-induced hippocampal neurotoxicity independently of PXR. Our findings suggest that glucocorticoids may be a potential therapeutic strategy for managing the neuronal side effects of PHT., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Authors.)

Immune checkpoint inhibitors (PD-1/PD-L1 and CTLA-4 blockade) have revolutionized the treatment landscape in non-small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO-IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

The self-powered sensor (SPS) is a sensor method that does not require the external power source and has the potential for portable detection of environmental contaminants. In this work, for the first time, a biomolecule-free SPS for detection of ultra-trace triazine endocrine disruptor atrazine (ATZ) with high sensitivity and selectivity is constructed using a glucose oxidase (GOD)-like cobalt metal-organic framework (Co-MOF) nanozyme-modified high-performance anode and a molecularly imprinted cathode. By modulating the size and morphology of the prepared materials, Co-MOF nanozyme with superior GOD-like property (Michaelis constant K m  = 15.8 mM) has been obtained and modified at the anode to catalyze glucose oxidation with high efficiency and provide energy continuously and stably for the SPS. The separation mode of anodic energy supply-cathodic recognition ensures the recognition effect without affecting the catalytic characteristic of Co-MOF and the output signal of the SPS. The designed SPS has a wide linear range of 1 pM-100 nM and a detection limit as low as 0.65 pM, as well as superior selectivity and good stability. The present work provides a promising approach for the design of self-powered sensors which can be extended to detection of a wider range of environmental pollutants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Importance: Typhoid fever is a life-threatening disease caused by Salmonella enterica serovar Typhi, resulting in a significant disease burden across developing countries. Historically, China was very much close to the global epicenter of typhoid, but the role of typhoid transmission within China and among epicenter remains overlooked in previous investigations. By using newly produced genomics on a national scale, we clarify the complex local and global transmission history of such a notorious disease agent in China spanning the most recent five decades, which largely undermines the global public health network., Competing Interests: The authors declare no conflict of interest.

Although the gut microbiota has been reported to influence osteoporosis risk, the individual species involved, and underlying mechanisms, remain largely unknown. We performed integrative analyses in a Chinese cohort of peri-/post-menopausal women with metagenomics/targeted metabolomics/whole-genome sequencing to identify novel microbiome-related biomarkers for bone health. Bacteroides vulgatus was found to be negatively associated with bone mineral density (BMD), which was validated in US white people. Serum valeric acid (VA), a microbiota derived metabolite, was positively associated with BMD and causally downregulated by B. vulgatus. Ovariectomized mice fed B. vulgatus demonstrated increased bone resorption and poorer bone micro-structure, while those fed VA demonstrated reduced bone resorption and better bone micro-structure. VA suppressed RELA protein production (pro-inflammatory), and enhanced IL10 mRNA expression (anti-inflammatory), leading to suppressed maturation of osteoclast-like cells and enhanced maturation of osteoblasts in vitro. The findings suggest that B. vulgatus and VA may represent promising targets for osteoporosis prevention/treatment., (© 2023. The Author(s).)

Introduction: Nephrotic syndrome (NS) is characterized by renal sodium and water retention. The mechanisms are not fully elucidated., Methods: The NS rat model was established by single intraperitoneal injection of 100 mg/kg puromycin aminonucleoside (PAN). The plasma electrolyte level and urinary sodium excretion were monitored dynamically. The changes of some sodium transporters, including epithelial Na + channel (ENaC), Na + /H + exchanger 3 (NHE3), Na + -K + -2Cl - cotransporter 2 (NKCC2) and Na + -Cl - cotransporter (NCC) in renal cortex at different time points and the level of peripheral circulation factors were detected., Results: The urinary sodium excretion of the model group increased significantly on the first day, then decreased compared with the control group, and there was no significant difference between the model group and the control group on the 12th day. The changes of peripheral circulation factors were not obvious. Some sodium transporters in renal cortex increased in varying degrees, while NKCC2 decreased significantly compared with the control group., Conclusions: The occurrence of NS edema may not be related to the angiotensin system. The decrease of urinary sodium excretion is independent of the development of albuminuria. During the 18 days of observation, it can be divided into three stages: sodium retention, sodium compensation, and simple water retention. The mechanism is related to the increased expression of α-ENaC, γ-ENaC, NHE3 and NCC in a certain period of time, the compensatory decrease of NKCC2 expression and the continuous increase of aquaporin 2 (AQP2) expression., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Immobilization-free sensors (IFSs), with no requirement of fixing the recognition element to the electrode surface, have received increasing attention due to their unique advantages of reusable electrodes, not being limited by the load of the recognition element, and not being easily changed to the structure of the probe. In the present work, an effective visible light-driven immobilization-free photoelectric aptasensor for ultrasensitive detection of atrazine (ATZ) was proposed based on a reusable BiOBr/Ag NP substrate electrode with ultrafast charge transfer. Controllable thiols were used as conditioning agents for the photoelectric signal. The ingeniously designed bifunctional graphene can act as not only a molecular "bridge" for the ATZ aptamer through a strong π-π stacking effect, obtaining a graphene-aptamer complex, serving as a homogeneous recognition element, but also a switch for signal modulation for quantitative detection of target substances. Benefiting from the synergistic effect of the above-mentioned factors, the proposed sensor is capable of ultrasensitive and highly selective detection of ATZ in real water samples with a low detection limit of 1.2 pM and a wide linear range from 5.0 pM to 10.0 nM. Furthermore, it shows high stability, good selectivity, and strong anti-interference ability. Thus, this work has provided a fresh perspective for designing advanced immobilization-free photoelectric sensors and convenient detection of environmental pollutants.

Ischemia/reperfusion injury (IRI) is a notable contributor to kidney injury, but effective prevention and treatment options are limited. The present study aimed to evaluate the impact of xanthohumol (XN), a kind of flavonoid, on renal IRI and its pathological process in rats. Rats and HK-2 cells were divided into five groups: Sham (control), IR [hypoxia-reoxygenation (HR)], IR (HR) + XN, IR (HR) + erastin or IR (HR) + XN + erastin. The effects of XN and erastin (a ferroptosis inducer) on IRI in rats were evaluated using blood urea nitrogen, plasma creatinine, glutathione, superoxide dismutase and malondialdehyde kits, western blotting, cell viability assay, hematoxylin and eosin staining and reactive oxygen species (ROS) detection. Nrf2 small interfering (si)RNA was used to investigate the role of the Nrf2/heme oxygenase (HO)-1 axis in XN-mediated protection against HR injury. Cell viability, ROS levels and expression of ferroptosis-related proteins were analyzed. Following IR, renal function of rats was severely impaired and oxidative stress and ferroptosis levels significantly increased. However, XN treatment decreased renal injury and inhibited oxidative stress and ferroptosis in renal tubular epithelial cells. Additionally, XN upregulated the Nrf2/HO-1 signaling pathway and Nrf2-siRNA reversed the renoprotective effect of XN. XN effectively decreased renal IRI by inhibiting ferroptosis and oxidative stress and its protective mechanism may be associated with the Nrf2/HO-1 signaling pathway., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Tang et al.)

With the increase in the survival rate of very preterm infants, the long-term neurodevelopmental outcomes of such infants have attracted more and more attention. Very preterm infants tend to develop movement disorders and psychological and behavioral problems, including cerebral palsy, developmental coordination disorders, autism spectrum disorders, attention deficit hyperactivity disorders, specific learning disorders, and intellectual developmental disorders. It is of vital importance to improve the long-term prognosis of very preterm infants, and early comprehensive intervention measures can minimize disability and achieve optimal parenting outcomes. This article provides a review of the research progress on the long-term neurodevelopmental outcomes in extremely preterm infants.