Vitamin D and major chronic diseases.

Numerous observational studies have demonstrated a significant inverse association between vitamin D status and the risk of major chronic disease, including type 2 diabetes (T2D), cardiovascular disease (CVD), and cancer. However, findings from Mendelian randomization (MR) studies and randomized controlled trials (RCTs) suggest minimal or no benefit of increased vitamin D levels. We provide an overview of recent literature linking vitamin D to major chronic diseases. Because emerging evidence indicates a potential threshold effect of vitamin D, future well-designed studies focused on diverse populations with vitamin D deficiency or insufficiency are warranted for a more comprehensive understanding of the effect of maintaining sufficient vitamin D status on the prevention of major chronic diseases.

METTL3 deficiency leads to ovarian insufficiency due to IL-1ß overexpression in theca cells.

Premature ovarian insufficiency (POI) is a clinical syndrome characterised by a decline in ovarian function in women before 40 years of age and is associated with oestradiol deficiency and a complex pathogenesis. However, the aetiology of POI is still unclear and effective preventative and treatment strategies are still lacking. Methyltransferase like 3 (METTL3) is an RNA methyltransferase that is involved in spermatogenesis, oocyte development and maturation, early embryonic development, and embryonic stem cell differentiation and formation, but its role in POI is unknown. In the present study, METTL3 deficiency in follicular theca cells was found to lead to reduced fertility in female mice, with a POI-like phenotype, and METTL3 knockout promoted ovarian inflammation. Further, a reduction in METTL3 in follicular theca cells led to a decrease in the m6A modification of pri-miR-21, which further reduced pri-miR-21 recognition and binding by DGCR8 proteins, leading to a decrease in the synthesis of mature miR-21-5p. Decrease of miR-21-5p promoted the secretion of interleukin-1ß (IL-1ß) from follicular theca cells. Acting in a paracrine manner, IL-1ß inhibited the cAMP-PKA pathway and activated the NF-κB pathway in follicular granulosa cells. This activation increased the levels of reactive oxygen species in granulosa cells, causing disturbances in the intracellular Ca2+ balance and mitochondrial damage. These cellular events ultimately led to granulosa cell apoptosis and a decrease in oestradiol synthesis, resulting in POI development. Collectively, these findings reveal how METTL3 deficiency promotes the expression and secretion of IL-1ß in theca cells, which regulates ovarian functions, and proposes a new theory for the development of POI disease.

Investigation of oxygen packaging to maintain beef color stability and microbiology safety after periods of long-term superchilled storage.

This study aimed to develop an appropriate modified atmosphere packaging (MAP) system for displayed beef steaks following long-term superchilled (-1 °C) storage. After superchilled storage for 0, 2, 8, or 16 weeks, beef loins were fabricated into steaks and displayed with 20%, 50%, or 80% O2-MAP under chilled conditions. At each storage point, after display for 0, 3, 7, or 10 days, instrumental color, myoglobin redox forms percentage, lipid oxidation, total viable count (TVC), and total volatile basic nitrogen (TVB-N) were evaluated. Meat color stability decreased, with prolonged storage period and display time. When the storage period was within 8 weeks, under all the above MAP conditions, the display time for the beef steaks was up to 10 days. Considering 80% O2-MAP promoted lipid oxidation, 50% and 80% O2-MAP were not recommended for displaying steaks for more than 10 and 7 days respectively after 16 weeks of storage. However, 20%, 50%, or 80% O2-MAP could maintain 3 days of microbial shelf-life according to TVC and TVB-N results. Additionally, after long-term superchilled storage for 16 weeks, the various O2 concentrations had minimal impact on microbiota succession during the MAP display period. Furthermore, beef steaks packaged under various MAP systems exhibited similar microbial compositions, with the dominant bacteria alternating between Lactobacillus and Carnobacterium. This study provided practical guidance for improving beef color stability after long-term superchilled storage.

Identification of a longevity gene through evolutionary rate covariation of insect mito-nuclear genomes.

Oxidative phosphorylation, essential for energy metabolism and linked to the regulation of longevity, involves mitochondrial and nuclear genes. The functions of these genes and their evolutionary rate covariation (ERC) have been extensively studied, but little is known about whether other nuclear genes not targeted to mitochondria evolutionarily and functionally interact with mitochondrial genes. Here we systematically examined the ERC of mitochondrial and nuclear benchmarking universal single-copy ortholog (BUSCO) genes from 472 insects, identifying 75 non-mitochondria-targeted nuclear genes. We found that the uncharacterized gene CG11837-a putative ortholog of human DIMT1-regulates insect lifespan, as its knockdown reduces median lifespan in five diverse insect species and Caenorhabditis elegans, whereas its overexpression extends median lifespans in fruit flies and C. elegans and enhances oxidative phosphorylation gene activity. Additionally, DIMT1 overexpression protects human cells from cellular senescence. Together, these data provide insights into the ERC of mito-nuclear genes and suggest that CG11837 may regulate longevity across animals.

High-Throughput Screening Strategy for Electrocatalysts for Selective Catalytic Oxidation of Formaldehyde to Formic Acid.

Electrocatalytic oxidation of formaldehyde (FOR) is an effective way to prevent the damage caused by formaldehyde and produce high-value products. A screening strategy of a single-layer MnO2-supported transition metal catalyst for the selective oxidation of formaldehyde to formic acid was designed by high-throughput density functional calculation. N-MnO2@Cu and MnO2@Cu are predicted to be potential FOR electrocatalysts with potential-limiting steps (PDS) of 0.008 and -0.009 eV, respectively. Electronic structure analysis of single-atom catalysts (SACs) shows that single-layer MnO2 can regulate the spin density of loaded transition metal and thus regulate the adsorption of HCHO (Ead), and Ead is volcanically distributed with the magnetic moment descriptor -|mM - mH|. In addition, the formula quantifies Ead and |mM - mH| to construct a volcano-type descriptor α describing the PDS [ΔG(*CHO)]. Other electronic and structural properties of SACs and α are used as input features for the GBR method to construct machine learning models predicting the PDS (R2 = 0.97). This study hopes to provide some insights into FOR electrocatalysts.

Association of Human Whole-blood NAD + Levels with Nabothian Cyst.

Objective: Little is known about the association between whole-blood nicotinamide adenine dinucleotide (NAD +) levels and nabothian cysts. This study aimed to assess the association between NAD + levels and nabothian cysts in healthy Chinese women. Methods: Multivariate logistic regression analysis was performed to analyze the association between NAD + levels and nabothian cysts. Results: The mean age was 43.0 ± 11.5 years, and the mean level of NAD + was 31.3 ± 5.3 µmol/L. Nabothian cysts occurred in 184 (27.7%) participants, with single and multiple cysts in 100 (15.0%) and 84 (12.6%) participants, respectively. The total nabothian cyst prevalence gradually decreased from 37.4% to 21.6% from Q1 to Q4 of NAD + and the prevalence of single and multiple nabothian cysts also decreased across the NAD + quartiles. As compared with the highest NAD + quartile (≥ 34.4 µmol/L), the adjusted odds ratios with 95% confidence interval of the NAD + Q1 was 1.89 (1.14-3.14) for total nabothian cysts. The risk of total and single nabothian cysts linearly decreased with increasing NAD + levels, while the risk of multiple nabothian cysts decreased more rapidly at NAD + levels of 28.0 to 35.0 µmol/L. Conclusion: Low NAD + levels were associated with an increased risk of total and multiple nabothian cysts.

The Impact of Music on Anxiety, Pain, and Blood Pressure in Ophthalmic Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVES: To evaluate the effectiveness of music therapy in reducing anxiety, pain, and vital sign changes in ophthalmic surgery patients. METHODS: An extensive search of databases, including PubMed, Embase, Web of Science, and Google Scholar, identified relevant studies up to Jan 2024. Selection of studies was conducted based on the PICOS criteria. The quality of methodology was assessed using the Cochrane risk-of-bias assessment tool and Review Manager 5.4. Meta-analysis comparing the control group and the music therapy group was performed using R and Stata/SE 15.1 random or fixed effects model. RESULTS: This meta-analysis included fifteen studies comprising 2098 participants. The analysis revealed that music therapy significantly reduced the risk of high anxiety levels as measured by Visual Analogue Scale (VAS) (I2 = 0%, RR(95%CI): 0.75(0.63, 0.88), p = 0.0006), indicating a substantial effect without heterogeneity. The Anxiety scores determined by State-Trait Anxiety Inventory-State (STAI-S) also showed a significant decrease (SMD(95%CI): -0.75(-0.88, -0.61), p < 0.0001), albeit with moderate heterogeneity (I² = 36%). Additionally, music therapy was associated with a reduction in intraoperative pain levels, with no observed heterogeneity (I2 = 0%, SMD(95%CI): -0.74(-0.93, -0.56), p < 0.0001). In contrast, music intervention did not significantly influence self-reported nervousness, relaxation, or satisfaction levels as determined by VAS. Regarding to physiological parameters, a marginal decrease in systolic blood pressure (SBP) was observed (SMD(95%CI): -0.42(-0.79, -0.04), p = 0.0286), with considerable heterogeneity (I² = 92%). Diastolic blood pressure (DBP) experienced a slight reduction (I² = 90%, SMD(95%CI): -0.45(-0.79, -0.11), p = 0.0088). However, no significant effect was observed on patients' heart rate (p = 0.0864). CONCLUSION: Music therapy effectively reduced anxiety and pain, and moderately improved vital signs in patients undergoing ophthalmic surgery, highlighting its role in enhancing patient well-being. Further in-depth RCTs are needed to confirm its efficacy.

Machine learning in prenatal MRI predicts postnatal ventricular abnormalities in fetuses with isolated ventriculomegaly.

OBJECTIVES: To evaluate the intracranial structures and brain parenchyma radiomics surrounding the occipital horn of the lateral ventricle in normal fetuses (NFs) and fetuses with ventriculomegaly (FVs), as well as to predict postnatally enlarged lateral ventricle alterations in FVs. METHODS: Between January 2014 and August 2023, 141 NFs and 101 FVs underwent 1.5 T balanced steady-state free precession (BSSFP), including 68 FVs with resolved lateral ventricles (FVM-resolved) and 33 FVs with stable lateral ventricles (FVM-stable). Demographic data and intracranial structures were analyzed. To predict the enlarged ventricle alterations of FVs postnatally, logistic regression models with 5-fold cross-validation were developed based on lateral ventricle morphology, blended-cortical or/and subcortical radiomics characteristics. Validation of the models' performance was conducted using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). RESULTS: Significant alterations in cerebral structures were observed between NFs and FVs (p < 0.05), excluding the maximum frontal horn diameter (FD). However, there was no notable distinction between the FVM-resolved and FVM-stable groups (all p > 0.05). Based on subcortical-radiomics on the aberrant sides of FVs, this approach exhibited high efficacy in distinguishing NFs from FVs in the training/validation set, yielding an impressive AUC of 1/0.992. With an AUC value of 0.822/0.743 in the training/validation set, the Subcortical-radiomics model demonstrated its ability to predict lateral ventricle alterations in FVs, which had the greatest predictive advantages indicated by DCA. CONCLUSIONS: Microstructural alterations in subcortical parenchyma associated with ventriculomegaly can serve as predictive indicators for postnatal lateral ventricle variations in FVs. CLINICAL RELEVANCE STATEMENT: It is critical to gain pertinent information from a solitary fetal MRI to anticipate postnatal lateral ventricle alterations in fetuses with ventriculomegaly. This approach holds the potential to diminish the necessity for recurrent prenatal ultrasound or MRI examinations. KEY POINTS: Fetal ventriculomegaly is a dynamic condition that affects postnatal neurodevelopment. Machine learning and subcortical-radiomics can predict postnatal alterations in the lateral ventricle. Machine learning, applied to single-fetal MRI, might reduce required antenatal testing.

Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer.

Metastasis remains a major challenge in the successful management of malignant diseases. The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon, stomach, and pancreatic cancers, as well as melanoma, breast cancer, and sarcoma. As an important factor that influences the development of metastatic liver cancer, alternative splicing drives the diversity of RNA transcripts and protein subtypes, which may provide potential to broaden the target space. In particular, the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence, progression, aggressiveness, and drug resistance of cancers caused by the selective splicing of specific genes. This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer. It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes, abnormal splicing, and the contribution of hypoxia to these changes during metastasis.

Optofluidic crystallithography for directed growth of single-crystalline halide perovskites.

Crystallization is a fundamental phenomenon which describes how the atomic building blocks such as atoms and molecules are arranged into ordered or quasi-ordered structure and form solid-state materials. While numerous studies have focused on the nucleation behavior, the precise and spatiotemporal control of growth kinetics, which dictates the defect density, the micromorphology, as well as the properties of the grown materials, remains elusive so far. Herein, we propose an optical strategy, termed optofluidic crystallithography (OCL), to solve this fundamental problem. Taking halide perovskites as an example, we use a laser beam to manipulate the molecular motion in the native precursor environment and create inhomogeneous spatial distribution of the molecular species. Harnessing the coordinated effect of laser-controlled local supersaturation and interfacial energy, we precisely steer the ionic reaction at the growth interface and directly print arbitrary single crystals of halide perovskites of high surface quality, crystallinity, and uniformity at a high printing speed of 102 µm s-1. The OCL technique can be potentially extended to the fabrication of single-crystal structures beyond halide perovskites, once crystallization can be triggered under the laser-directed local supersaturation.

Evaluating the clinical efficacy and safety of concurrent chemoradiotherapy with cisplatin and nab-paclitaxel in postoperative early-stage cervical cancer.

OBJECTIVE: A preclinical study showed that nab-paclitaxel acted as a radiosensitizer and improved tumor radiotherapy in a supra-additive manner. In this study, we aimed to evaluate the clinical efficacy and safety of concurrent chemoradiotherapy (CCRT) with cisplatin and nab-paclitaxel in postoperative early-stage cervical cancer with an unfavorable prognosis. METHODS: Eligible patients with stage IB1-IIA2 (FIGO 2009) cervical carcinoma were recruited retrospectively between August 2018 to May 2021. Patients in both the cisplatin and nab-paclitaxel groups received postoperative radiotherapy and weekly intravenous cisplatin 40 mg/m2 or nab-paclitaxel 100 mg concurrently. An analysis of overall survival, progression-free survival, and adverse reactions was conducted. RESULTS: A total of 105 early-stage cervical cancer patients were included into our study. The median follow-up time was 38.7 months. The 3-year overall survival and progression-free survival in both group was similar. The cycles of chemotherapy in the cisplatin group were less than those in the nab-paclitaxel group (4.5 vs. 5.0; p = 0.001). Patients in the cisplatin group had a significantly higher frequency of hematological adverse events than patients in the nab-paclitaxel group (P < 0.05). Patients in the cisplatin group had a significantly higher frequency of grade 3-4 leukopenia (46.1% vs. 18.9%; P = 0.03), grade 1-2 thrombocytopenia (32.7% vs. 9.5%; P = 0.014) than patients in the nab-paclitaxel group. Gastrointestinal reactions, such as vomiting, nausea, and anorexia were significantly reduced in the nab-paclitaxel group compared with those in the cisplatin group. Regarding the effects on alopecia, the incidence rate of the nab-paclitaxel group was higher than that of the cisplatin group (P = 0.001). There were no differences between the groups in terms of other adverse reactions. CONCLUSION: The results of this study indicate that nab-paclitaxel-based concurrent radiotherapy is tolerable and effective, and can be considered an alternative to cisplatin chemotherapy.

Detection and Characterization of the Metabolites of Ciwujianoside B in Rats Based on UPLC-Fusion Lumos Orbitrap Mass Spectrometry.

We previously conducted a systematic study on the metabolic process and products of hederasaponin B in rats. We hypothesized that the sugar chain structures play a key role in the metabolism of triterpenoid saponins. To verify this hypothesis, we conducted metabolic research on ciwujianoside B ascribed to the same sugar chains and a distinct aglycone and compared it with hederasaponin B. Specifically, we collected feces, urine, and plasma of rats after gavage with ciwujianoside B and identified 42 metabolites by UPLC-Fusion Lumos Orbitrap mass spectrometry. Finally, ciwujianoside B metabolism and hederasaponin B metabolism were compared, reaching the following conclusions: (i) more than 40 metabolites were identified in both, with the majority of metabolites identified in feces; (ii) the corresponding metabolic pathways in vivo were basically similar, including deglycosylation, acetylation, hydroxylation, glucuronidation, oxidation, and glycosylation; and (iii) deglycosylation was considered the main metabolic reaction, and its metabolites accounted for approximately 50% of all metabolites. Overall, this study provides a foundation for further research on the metabolism of triterpenoid saponins.

Active control of nonreciprocal near-field radiative heat transfer with a drift-current biased graphene/α-MoO3 heterostructure.

The interaction between the drift-current biased graphene plasmonics and the hyperbolic phonon polaritons of α-MoO3 provides a promising way to manipulate near-field radiation heat transfer (NFRHT). Through examination of the drift biased graphene/α-MoO3 heterostructure, it has been discovered that drift-current applied to the graphene effectively enhances photon tunneling. Consequently, they dynamically modulate the coupling effect of the two excitations, thereby offering a reliable pathway for the modulation of NFRHT. Furthermore, the influencing mechanism of vacuum gaps on nonreciprocal NFRHT with different drift-current rates is revealed, and it is discovered that the vacuum gaps can filter the nonreciprocal surface plasmon polaritons with high nonreciprocity. Our findings make it possible to manipulate nanoscale thermal rectification and noncontact thermal modulation.

Defocus-integration interferometric scattering microscopy for speckle suppression and enhancing nanoparticle detection on a substrate.

Direct optical detection and imaging of single nanoparticles on a substrate in wide field underpin vast applications across different research fields. However, speckles originating from the unavoidable random surface undulations of the substrate ultimately limit the size of the decipherable nanoparticles by the current optical techniques, including the ultrasensitive interferometric scattering microscopy (iSCAT). Here, we report a defocus-integration iSCAT to suppress the speckle noise and to enhance the detection and imaging of single nanoparticles on an ultra-flat glass substrate and a silicon wafer. In particular, we discover distinct symmetry properties of the scattering phase between the nanoparticle and the surface undulations that cause the speckles. Consequently, we develop the defocus-integration technique to suppress the speckles. We experimentally achieve an enhancement of the signal-to-noise ratio by 6.9 dB for the nanoparticle detection. We demonstrate that the technique is generally applicable for nanoparticles of various materials and for both low and high refractive index substrates.

Patterns of distant metastasis and survival outcomes in de novo metastatic breast cancer according to age groups.

Background: Is de novo metastatic breast cancer (dnMBC) the same disease in the elderly as in younger breast cancer remains unclear. This study aimed to determine the metastatic patterns and survival outcomes in dnMBC according to age groups. Methods: We included patients from the Surveillance Epidemiology and End Results program. Chi-square test, multivariate logistic regression analyses, and multivariate Cox regression models were used for statistical analyses. Results: A total of 17719 patients were included. There were 3.6% (n=638), 18.6% (n=3290), 38.0% (n=6725), and 39.9% (n=7066) of patients aged <35, 35-49, 50-64, and ≥65 years, respectively. Older patients had a significantly higher risk of lung metastasis and a significantly lower risk of liver metastasis. There were 19.1%, 25.6%, 30.9%, and 35.7% of patients with lung metastasis in those aged <35, 35-49, 50-64, and ≥65 years, respectively. Moreover, the proportion of liver metastasis was 37.6%, 29.5%, 26.3%, and 19.2%, respectively. Age was the independent prognostic factor associated with breast cancer-specific survival (BCSS) and overall survival (OS). Those aged 50-64 years had significantly inferior BCSS (P<0.001) and OS (P<0.001) than those aged <35 years. Patients aged ≥65 years also had significantly lower BCSS (P<0.001) and OS (P<0.001) than those aged <35 years. However, similar outcomes were found between those aged 35-49 and <35 years. Conclusion: Our study suggests that different age groups may affect the metastatic patterns among patients with dnMBC and the survival of younger patients is more favorable than those of older patients.

Blood-brain barrier disruption and hemorrhagic transformation in acute stroke before endovascular reperfusion therapy.

Background and purpose: Early blood-brain barrier (BBB) disruption in patients with acute ischemic stroke (AIS) can be detected on perfusion computed tomography (PCT) images before undergoing reperfusion therapy. In this study, we aimed to determine whether early disruption of the BBB predicts intracranial hemorrhage transformation (HT) in patients with AIS undergoing endovascular therapy and further identify factors influencing BBB disruption. Methods: We retrospectively analyzed general clinical and imaging data derived from 159 consecutive patients with acute anterior circulation stroke who were admitted to the Department of Neurology of the First Hospital of Jilin University, and who underwent endovascular treatment between January 1, 2021, and March 31, 2023. We evaluated the relationship between BBB destruction and intracranial HT before endovascular reperfusion therapy and examined the risk factors for early BBB destruction. Results: A total of 159 patients with assessable BBB leakage were included. The median (interquartile range, IQR) age was 63 (54-70) years, 108 (67.9%) patients were male, and the median baseline National Institutes of Health Stroke Scale (NHISS) score was 12 (10-15). Follow-up non-contrast computed tomography (NCCT) detected HT in 63 patients. After logistic regression modeling adjustment, we found that BBB leakage in the true leakage area was slightly more than 2-fold risk of HT (odds ratio [OR], 2.01; 95% confidence interval [CI] 1.02-3.92). Heart rate was also associated with HT (OR, 1.03, 95% CI, 1.00-1.05). High Blood-brain barrier permeability (BBBP) in the true leakage area was positively correlated with infarct core volume (OR, 1.03; 95% CI, 1.01-1.05). Conclusion: Early BBB destruction before endovascular reperfusion therapy was associated with HT, whereas high BBBP correlated positively with infarct core volume.

Polygenic risk-stratified screening for nasopharyngeal carcinoma in high-risk endemic areas of China: a cost-effectiveness study.

Background: Nasopharyngeal carcinoma (NPC) has an extremely high incidence rate in Southern China, resulting in a severe disease burden for the local population. Current EBV serologic screening is limited by false positives, and there is opportunity to integrate polygenic risk scores for personalized screening which may enhance cost-effectiveness and resource utilization. Methods: A Markov model was developed based on epidemiological and genetic data specific to endemic areas of China, and further compared polygenic risk-stratified screening [subjects with a 10-year absolute risk (AR) greater than a threshold risk underwent EBV serological screening] to age-based screening (EBV serological screening for all subjects). For each initial screening age (30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64, and 65-69 years), a modeled cohort of 100,000 participants was screened until age 69, and then followed until age 79. Results: Among subjects aged 30 to 54 years, polygenic risk-stratified screening strategies were more cost-effective than age-based screening strategies, and almost comprised the cost-effectiveness efficiency frontier. For men, screening strategies with a 1-year frequency and a 10-year absolute risk (AR) threshold of 0.7% or higher were cost-effective, with an incremental cost-effectiveness ratio (ICER) below the willingness to pay (¥203,810, twice the local per capita GDP). Specifically, the strategies with a 10-year AR threshold of 0.7% or 0.8% are the most cost-effective strategies, with an ICER ranging from ¥159,752 to ¥201,738 compared to lower-cost non-dominated strategies on the cost-effectiveness frontiers. The optimal strategies have a higher probability (29.4-35.8%) of being cost-effective compared to other strategies on the frontier. Additionally, they reduce the need for nasopharyngoscopies by 5.1-27.7% compared to optimal age-based strategies. Likewise, for women aged 30-54 years, the optimal strategy with a 0.3% threshold showed similar results. Among subjects aged 55 to 69 years, age-based screening strategies were more cost-effective for men, while no screening may be preferred for women. Conclusion: Our economic evaluation found that the polygenic risk-stratified screening could improve the cost-effectiveness among individuals aged 30-54, providing valuable guidance for NPC prevention and control policies in endemic areas of China.

LC-MS-based metabolomics reveals metabolite dynamic changes of beef after superchilling early post-mortem.

To explore the underlying mechanisms by which superchilling (SC, -3 °C within 5 h of slaughter) improves beef tenderness, an untargeted metabolomics strategy was employed. M. Longissimus lumborum (LL) muscles from twelve beef carcasses were assigned to either SC or very fast chilling (VFC, 0 °C within 5 h of slaughter) treatments, with conventional chilling (CC, 0 âˆ¼ 4 °C until 24 h post-mortem) serving as the control (6 per group). Biochemical properties and metabolites were investigated during the early post-mortem period. The results showed that the degradation of µ-calpain and caspase 3 occurred earlier in SC treated sample, which might be attributed to the accelerated accumulation of free Ca2+. The metabolomic profiles of samples from the SC and CC treatments were clearly distinguished based on partial least squares-discriminant analysis (PLS-DA) at each time point. It is noteworthy that more IMP and 4-hydroxyproline were found in the comparison between SC and CC treatments. According to the results of metabolic pathways analysis and the correlation analysis between traits related to tenderness and metabolites with significant differences (SC vs. CC), it can be suggested that the tenderization effect of the SC treatment may be related to the alteration of arginine and proline metabolism, and purine metabolism in the early post-mortem phase.

Dysregulation of Gut Microbiota-Derived Neuromodulatory Amino Acid Metabolism in Human Immunodeficiency Virus-Associated Neurocognitive Disorder: An Integrative Metagenomic and Metabolomic Analysis.

OBJECTIVE: Although accumulating evidence implicating altered gut microbiota in human immunodeficiency virus (HIV) infection and neurodegenerative disorders; however, the association between dysbiosis of the gut microbiota and metabolites in the pathogenesis of HIV-associated neurocognitive disorder (HAND) remains unclear. METHODS: Fecal and plasma samples were obtained from 3 cohorts (HAND, HIV-non-HAND, and healthy controls), metagenomic analysis and metabolomic profiling were performed to investigate alterations in the gut microbial composition and circulating metabolites in HAND. RESULTS: The gut microbiota of people living with HIV (PLWH) had an increased relative abundance of Prevotella and a decreased relative abundance of Bacteroides. In contrast, Prevotella and Megamonas were substantially decreased, and Bacteroides and Phocaeicola were increased in HAND patients. Moreover, untargeted metabolomics identified several neurotransmitters and certain amino acids associated with neuromodulation, and the differential metabolic pathways of amino acids associated with neurocognition were depleted in HAND patients. Notably, most neuromodulatory metabolites are associated with an altered abundance of specific gut bacteria. INTERPRETATION: Our findings provide new insights into the intricate interplay between the gut and microbiome-brain axis in the pathogenesis of HAND, highlighting the potential for developing novel therapeutic strategies that specifically target the gut microbiota. ANN NEUROL 2024.

Transcriptome sequencing and metabolome analysis reveal the molecular mechanism of Salvia miltiorrhiza in response to drought stress.

Salvia miltiorrhiza is commonly used as a Chinese herbal medicine to treat different cardiovascular and cerebrovascular illnesses due to its active ingredients. Environmental conditions, especially drought stress, can affect the yield and quality of S. miltiorrhiza. However, moderate drought stress could improve the quality of S. miltiorrhiza without significantly reducing the yield, and the mechanism of this initial drought resistance is still unclear. In our study, transcriptome and metabolome analyses of S. miltiorrhiza under different drought treatment groups (CK, A, B, and C groups) were conducted to reveal the basis for its drought tolerance. We discovered that the leaves of S. miltiorrhiza under different drought treatment groups had no obvious shrinkage, and the malondialdehyde (MDA) contents as well as superoxide dismutase (SOD) and peroxidase (POD) activities dramatically increased, indicating that our drought treatment methods were moderate, and the leaves of S. miltiorrhiza began to initiate drought resistance. The morphology of root tissue had no significant change under different drought treatment groups, and the contents of four tanshinones significantly enhanced. In all, 5213, 6611, and 5241 differentially expressed genes (DEGs) were shared in the A, B, and C groups compared with the CK group, respectively. The results of KEGG and co-expression analysis showed that the DEGs involved in plant-pathogen interactions, the MAPK signaling pathway, phenylpropanoid biosynthesis, flavonoid biosynthesis, and plant hormone signal transduction responded to drought stress and were strongly correlated with tanshinone biosynthesis. Furthermore, the results of metabolism analysis indicated that 67, 72, and 92 differentially accumulated metabolites (DAMs), including fumarate, ferulic acid, xanthohumol, and phytocassanes, which were primarily involved in phenylpropanoid biosynthesis, flavonoid biosynthesis, and diterpenoid biosynthesis pathways, were detected in these groups. These discoveries provide valuable information on the molecular mechanisms by which S. miltiorrhiza responds to drought stress and will facilitate the development of drought-resistant and high-quality S. miltiorrhiza production.