Correlation between Serum 25 (OH) D Levels with Insulin Resistance and Metabolic Associated Fatty Liver Disease - A Retrospective Study based on Chinese Patients with Newly Diagnosed Type 2 Diabetes Mellitus.

AIMS: The objective of this study was to investigate the correlation between serum 25 hydroxyvitamin D [25(OH)D] levels and insulin resistance, as well as metabolic associated fatty liver disease (MAFLD) in newly diagnosed with type 2 diabetes mellitus(T2DM) patients. METHOD: A retrospective analysis was conducted on 491 T2DM patients who were newly diagnosed between January 2017 and August 2022 at Peking University International Hospital. These patients were categorized into three groups based on their 25(OH)D levels. RESULTS: The prevalence of MAFLD was significantly elevated in both the Vitamin D(VD) deficiency group and the VD insufficiency group compared to the VD sufficiency group (χ2 = 6.51, p<0.05). The patients in the VD sufficiency group had lower levels of insulin resistance，as assessed by the homeostasis model assessment when compared to the VD deficiency group and the VD insufficiency group (F = 8.61，p < 0.05). Additionally, the VD sufficiency group demonstrated higher levels of ß cell function in comparison to the other two groups(p<0.05， respectively). (2) A significant negative correlation was observed between 25(OH)D levels and insulin resistance, as assessed by the homeostasis model assessment in T2DM patients(r=-0.33，p<0.05 for females; r=-0.32，p<0.05 for males). (3) In male patients, 25(OH)D was identified as a protective factor against MAFLD(OR = 0.42;95%CI:0.19-0.95;p<0.05). Meanwhile，in female patients, 25(OH)D was also associated with a reduced risk of MAFLD(OR = 0.35;95%CI 0.17-0.89;p<0.05). Additionally, the study determined that the threshold values for 25(OH)D were 15.06 ng/ml in female patients and 18.79 ng/ml in male patients for predicting MAFLD. CONCLUSION: In newly diagnosed with T2DM patients, the level of 25(OH)D may be related to insulin resistance and ß cell secretion function independently and VD deficiency is an independent risk factor for MAFLD in patients with newly diagnosed T2DM.

DLM-GelMA/tumor slice sandwich structured tumor on a chip for drug efficacy testing.

The in vitro recapitulation of tumor microenvironment is of great interest to preclinical screening of drugs. Compared with culture of cell lines, tumor organ slices can better preserve the complex tumor architecture and phenotypic activity of native cells, but are limited by their exposure to fluid shear and gradual degradation under perfusion culture. Here, we established a decellularized liver matrix (DLM)-GelMA "sandwich" structure and a perfusion-based microfluidic platform to support long-term culture of tumor slices with excellent structural integrity and cell viability over 7 days. The DLM-GelMA was able to secrete cytokines and growth factors while providing shear protection to the tumor slice via the sandwich structure, leading to the preservation of the tumor microenvironment where immune cells (CD3, CD8, CD68), tumor-associated fibroblasts (α-SMA), and extracellular matrix components (collagen I, fibronectin) were well maintained. Furthermore, this chip presented anti-tumor efficacy at cisplatin (20 µM) on tumor patients, demonstrating our platform's efficacy to design patient-specific treatment regimens. Taken together, the successful development of this DLM-GelMA sandwich structure on the chip could faithfully reflect the tumor microenvironment and immune response, accelerating the screening process of drug molecules and providing insights for practical medicine.

TikTok and teen mental health: an analysis of user-generated content and engagement.

BACKGROUND: TikTok is a social media mobile application that is widely used by adolescents, and has the potential to serve as a revolutionary platform for public and mental health discourse, education, and intervention. OBJECTIVE: Our study aimed to describe the content and engagement metrics of the hashtag #teenmentalhealth on TikTok. METHODS: In this study, we: (a) conducted a directed content analysis of the Top 100 TikTok videos tagged with #teenmentalhealth, and (b) collected data on video engagements (views, likes, saves, and shares) and computed view-based engagement rates. RESULTS: The videos collectively garnered 144,320,591 views; 28,289,655 likes; 219,780 comments; 1,971,492 saves; and 478,696 shares. Most of the generated content were from teens and therapists. Engagement metrics revealed strong user engagement rates across user types. The most prevalent content categories represented across videos were personal experience, coping techniques or treatment, humor, interpersonal relationships, and health campaign. The content categories with the highest engagement rates were relatable media representation, health campaign, social isolation, and humor. Only a single video incorporated evidence-based treatment content. CONCLUSION: TikTok facilitates communication and information dissemination on teen mental health. Future research should focus on improving the quality and credibility of digital content while maintaining engagement through creativity, self-expression, and relatability. Use of popular social media platforms and community-engaged research to disseminate evidence-based content may help bridge the translational research gap.

Impairment in acquisition of conditioned fear in people with depressive symptoms.

Background: Depression is one of the primary global public health issues, and there has been a dramatic increase in depression levels among young people over the past decade. The neuroplasticity theory of depression postulates that a malfunction in neural plasticity, which is responsible for learning, memory, and adaptive behavior, is the primary source of the disorder's clinical manifestations. Nevertheless, the impact of depression symptoms on associative learning remains underexplored. Methods: We used the differential fear conditioning paradigm to investigate the effects of depressive symptoms on fear acquisition and extinction learning. Skin conductance response (SCR) is an objective evaluation indicator, and ratings of nervousness, likeability, and unconditioned stimuli (US) expectancy are subjective evaluation indicators. In addition, we used associability generated by a computational reinforcement learning model to characterize the skin conductance response. Results: The findings indicate that individuals with depressive symptoms exhibited significant impairment in fear acquisition learning compared to those without depressive symptoms based on the results of the skin conductance response. Moreover, in the discrimination fear learning task, the skin conductance response was positively correlated with associability, as estimated by the hybrid model in the group without depressive symptoms. Additionally, the likeability rating scores improved post-extinction learning in the group without depressive symptoms, and no such increase was observed in the group with depressive symptoms. Conclusion: The study highlights that individuals with pronounced depressive symptoms exhibit impaired fear acquisition and extinction learning, suggesting a possible deficit in associative learning. Employing the hybrid model to analyze the learning process offers a deeper insight into the associative learning processes of humans, thus allowing for improved comprehension and treatment of these mental health problems.

Combining transcriptome and metabolome analysis to understand the response of sorghum to Melanaphis sacchari.

BACKGROUND: The sorghum aphid Melanaphis sacchari (Zehntner) (Homoptera: Aphididae) is an important insect in the late growth phase of sorghum (Sorghum bicolor L.). However, the mechanisms of sorghum response to aphid infestation are unclear. RESULTS: In this paper, the mechanisms of aphid resistance in different types of sorghum varieties were revealed by studying the epidermal cell structure and performing a transcriptome and metabolome association analysis of aphid-resistant and aphid-susceptible varieties. The epidermal cell results showed that the resistance of sorghum to aphids was positively correlated with epidermal cell regularity and negatively correlated with the intercellular space and leaf thickness. Transcriptome and metabolomic analyses showed that differentially expressed genes in the resistant variety HN16 and susceptible variety BTX623 were mainly enriched in the flavonoid biosynthesis pathway and differentially expressed metabolites were mainly related to isoflavonoid biosynthesis and flavonoid biosynthesis. The q-PCR results of key genes were consistent with the transcriptome expression results. Meanwhile, the metabolome test results showed that after aphidinfestation, naringenin and genistein were significantly upregulated in the aphid-resistant variety HN16 and aphid-susceptible variety BTX623 while luteolin was only significantly upregulated in BTX623. These results show that naringenin, genistein, and luteolin play important roles in plant resistance to aphid infestation. The results of exogenous spraying tests showed that a 1‰ concentration of naringenin and genistein is optimal for improving sorghum resistance to aphid feeding. CONCLUSIONS: In summary, the physical properties of the sorghum leaf structure related to aphid resistance were studied to provide a reference for the breeding of aphid-resistant varieties. The flavonoid biosynthesis pathway plays an important role in the response of sorghum aphids and represents an important basis for the biological control of these pests. The results of the spraying experiment provide insights for developing anti-aphid substances in the future.

The role of pyroptosis in heart failure and related traditional chinese medicine treatments.

Pyroptosis is a type of programmed cell death that is mediated by both typical and atypical pathways and ultimately leads to the lysis and rupture of cell membranes and the release of proinflammatory factors, triggering an intense inflammatory response. Heart failure (HF) is a serious and terminal stage of various heart diseases. Myocardial hypertrophy, myocardial fibrosis, ventricular remodeling, oxidative stress, the inflammatory response and cardiomyocyte ionic disorders caused by various cardiac diseases are all risk factors for and aggravate HF. Numerous studies have shown that pyroptosis can induce and exacerbate these reactions, causing progression to HF. Therefore, targeting pyroptosis is a promising strategy to treat HF. This paper summarizes the role of pyroptosis in the development of HF and the underlying mechanism involved. Recent research progress on the ability of traditional Chinese medicine (TCM) extracts and formulas to inhibit pyroptosis and treat HF was summarized, and some traditional Chinese medicine extracts and formulas can alleviate different types of HF, including heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), and heart failure with midrange ejection fraction (HFmrEF), by targeting pyroptosis. These findings may provide new ideas and evidence for the treatment or adjuvant treatment of HF by targeting pyroptosis.

Oxygen Vacancy-Enhanced Ni3N-CeO2/NF Nanoparticle Catalysts for Efficient and Stable Electrolytic Water Splitting.

Highly efficient and cost-effective electrocatalysts are of critical significance in the domain of water electrolysis. In this study, a Ni3N-CeO2/NF heterostructure is synthesized through a facile hydrothermal technique followed by a subsequent nitridation process. This catalyst is endowed with an abundance of oxygen vacancies, thereby conferring a richer array of active sites. Therefore, the catalyst demonstrates a markedly low overpotential of 350 mV for the Oxygen Evolution Reaction (OER) at 50 mA cm-2 and a low overpotential of 42 mV for the Hydrogen Evolution Reaction (HER) at 10 mA cm-2. Serving as a dual-function electrode, this electrocatalyst is employed in overall water splitting in alkaline environments, demonstrating impressive efficiency at a cell voltage of 1.52 V of 10 mA cm-2. The in situ Raman spectroscopic analysis demonstrates that cerium dioxide (CeO2) facilitates the rapid reconfiguration of oxygen vacancy-enriched nickel oxyhydroxide (NiOOH), thereby enhancing the OER performance. This investigation elucidates the catalytic role of CeO2 in augmenting the OER efficiency of nickel nitride (Ni3N) for water electrolysis, offering valuable insights for the design of high-performance bifunctional catalysts tailored for water splitting applications.

Polyurea-urethane Temperature-responsive Hydrogels for Sustained Delivery of Anti-VEGF Therapeutics.

Temperature-responsive hydrogels, or thermogels, have emerged as a leading platform for sustained delivery of both small molecule drugs and macromolecular biologic therapeutics. Although thermogel properties can be modulated by varying the polymer's hydrophilic-hydrophobic balance, molecular weight and degree of branching, varying the supramolecular donor-acceptor interactions on the polymer remains surprisingly overlooked. Herein, to study the influence of enhanced hydrogen bonding on thermogelation, we synthesized a family of amphiphilic polymers containing urea and urethane linkages using quinuclidine as an organocatalyst. Our findings showed that the presence of strongly hydrogen bonding urea linkages significantly enhanced polymer hydration in water, in turn affecting hierarchical polymer self-assembly and macroscopic gel properties such as sol-gel phase transition temperature and gel stiffness. Additionally, analysis of the sustained release profiles of Aflibercept, an FDA-approved protein biologic for anti-angiogenic treatment, showed that urea bonds on the thermogel were able to significantly alter the drug release mechanism and kinetics compared to usage of polyurethane gels of similar composition and molecular weight. Our findings demonstrate the unrealized possibility of modulating gel properties and outcomes of sustained drug delivery through judicious variation of hydrogen bonding motifs on the polymer structure.

Effects of Ultrasound-Guided Thoracic Paravertebral Nerve Block Combined with Perineural or IV Dexmedetomidine on Acute and Chronic Pain After Thoracoscopic Resection of Lung Lesions: A Double-Blind Randomized Trial.

Background: Thoracic paravertebral block (TPVB) analgesia can be prolonged by local anesthetic adjuvants such as dexmedetomidine. This study aimed to evaluate the two administration routes of dexmedetomidine on acute pain and chronic neuropathic pain (NeuP) prevention compared with no dexmedetomidine. Methods: A total of 216 patients were randomized to receive TPVB using 0.4% ropivacaine alone (R Group), with perineural dexmedetomidine 0.5 µg·kg-1 (RD0.5 Group) or 1.0 µg·kg-1 (RD1.0 Group), or intravenous (IV) dexmedetomidine 0.5 µg·kg-1·h-1 (RDiv Group). The primary outcome was the incidence of chronic NeuP, defined as a Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain score > 12 points at 3-month after surgery. Results: (1) For the primary outcome, RD0.5 Group and RD1.0 Group demonstrated a decreased incidence of chronic NeuP at 3-month after surgery; (2) Compared with R Group, RDiv Group, RD0.5 Group, and RD1.0 Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of oral morphine equivalent (OME) and improve QOD-15 at POD1; (3) Compared with RDiv Group, RD0.5 Group and RD1.0 Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of postoperative OME and improve QOD-15 at POD1; (4) Compared with RD0.5 Group, RD1.0 Group effectively reduced VAS scores at rest at 12 and 24-h after surgery, VAS scores in movement and Prince-Henry Pain scores at 12-h after surgery. However, RD1.0 Group showed an increased incidence of drowsiness. Conclusion: Perineural or IV dexmedetomidine are similarly effective in reducing acute pain, but only perineural dexmedetomidine reduced chronic NeuP. Moreover, considering postoperative complications such as drowsiness, perineural dexmedetomidine (0.5 µg·kg-1) may be a more appropriate choice. Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200058982).

Overexpression of arginase gene CAR1 renders yeast Saccharomyces cerevisiae acetic acid tolerance.

Acetic acid is a common inhibitor present in lignocellulose hydrolysate, which inhibits the ethanol production by yeast strains. Therefore, the cellulosic ethanol industry requires yeast strains that can tolerate acetic acid stress. Here we demonstrate that overexpressing a yeast native arginase-encoding gene, CAR1, renders Saccharomyces cerevisiae acetic acid tolerance. Specifically, ethanol yield increased by 27.3% in the CAR1-overexpressing strain compared to the control strain under 5.0 g/L acetic acid stress. The global intracellular amino acid level and compositions were further analyzed, and we found that CAR1 overexpression reduced the total amino acid content in response to acetic acid stress. Moreover, the CAR1 overexpressing strain showed increased ATP level and improved cell membrane integrity. Notably, we demonstrated that the effect of CAR1 overexpression was independent of the spermidine and proline metabolism, which indicates novel mechanisms for enhancing yeast stress tolerance. Our studies also suggest that CAR1 is a novel genetic element to be used in synthetic biology of yeast for efficient production of fuel ethanol.

METTL14 inhibits the malignant processes of gastric cancer cells by promoting N6-methyladenosine (m6A) methylation of TAF10.

N6-methyladenosine (m6A) methylation mediates cancer development by regulating cell proliferation and metastasis. This study aimed to identify whether methyltransferase 14 (METTL14) affects gastric cancer (GC) cellular functions and its underlying mechanism. METTL14 and TATA-box binding protein associated factor 10 (TAF10) levels were examined using quantitative real-time PCR, immunohistochemical assay, and Western blot. Biological functions were assessed using cell counting kit-8, colony formation, and transwell assays. The interaction between METTL14 and TAF10 was analyzed using RNA immunoprecipitation, methylated RNA immunoprecipitation, and luciferase reporter assay. A xenograft tumor mouse model was established to assess the role of METTL14 in vivo. The results suggested that METTL14 was low expressed and TAF10 was highly expressed in GC tissues and cells. METTL14 overexpression inhibited GC cell viability, colony, migration, and invasion. TAF10 was predicted and confirmed to be negatively related to METTL14. METTL14 promoted m6A methylation of TAF10 and inhibited TAF10 stability. Moreover, TAF10 counteracted the cellular behaviors regulated by METTL14. Overexpression of METTL14 inhibited tumor growth and histopathology. In conclusion, METTL14 inhibits GC progression by attenuating GC cell proliferation, migration, and invasion. Mechanistically, METTL14 promoted m6A methylation of TAF10, suppressed the stability of TAF10, and thus downregulated the TAF10 levels, These results provide a new insight into GC therapy.

The association between the scarlet fever and meteorological factors, air pollutants and their interactions in children in northwest China.

Scarlet fever (SF) is an acute respiratory transmitted disease that primarily affects children. The influence of meteorological factors and air pollutants on SF in children has been proved, but the relevant evidence in Northwest China is still lacking. Based on the weekly reported cases of SF in children in Lanzhou, northwest China, from 2014 to 2018, we used geographical detectors, distributed lag nonlinear models (DLNM), and bivariate response models to explore the influence of meteorological factors and air pollutants with SF. It was found that ozone (O3), carbon monoxide (CO), sulfur dioxide (SO2), temperature, pressure, water vapor pressure and wind speed were significantly correlated with SF based on geographical detectors. With the median as reference, the influence of high temperature, low pressure and high pressure on SF has a risk effect (relative risk (RR) > 1), and under extreme conditions, the dangerous effect was still significant. High O3 had the strongest effect at a 6-week delay, with an RR of 5.43 (95%CI: 1.74,16.96). The risk effect of high SO2 was strongest in the week of exposure, and the maximum risk effect was 1.37 (95%CI: 1.08,1.73). The interactions showed synergistic effects between high temperatures and O3, high pressure and high SO2, high nitrogen dioxide (NO2) and high particulate matter with diameter of less than 10 µm (PM10), respectively. In conclusion, high temperature, pressure, high O3 and SO2 were the most important factors affecting the occurrence of SF in children, which will provide theoretical support for follow-up research and disease prevention policy formulation.

Up-regulating GABA transporter-3 in the zona incerta prevents surgery-induced memory impairment in mice.

Clinical surgery can lead to severe neuroinflammation and cognitive dysfunctions. It has been reported that astrocytes mediate memory formation and postoperative cognitive dysfunction (POCD), however, the thalamic mechanism of astrocytes in mediating POCD remains unknown. Here, we report that reactive astrocytes in zona incerta (ZI) mediate surgery-induced recognition memory impairment in male mice. Immunostaining results showed that astrocytes are activated with GABA transporter-3 (GAT-3) being down-expressed, and neurons were suppressed in the ZI. Besides, our work revealed that reactive astrocytes caused increased tonic current in ZI neurons. Up-regulating the expression of GAT-3 in astrocytes ameliorates surgery-induced recognition memory impairment. Together, our work demonstrates that the reactive astrocytes in the ZI play a crucial role in surgery-induced memory impairment, which provides a new target for the treatment of surgery-induced neural dysfunctions.

Development of a Longitudinal Prostate Cancer Transcriptomic and Clinical Data Linkage.

Importance: Although tissue-based gene expression testing has become widely used for prostate cancer risk stratification, its prognostic performance in the setting of clinical care is not well understood. Objective: To develop a linkage between a prostate genomic classifier (GC) and clinical data across payers and sites of care in the US. Design, Setting, and Participants: In this cohort study, clinical and transcriptomic data from clinical use of a prostate GC between 2016 and 2022 were linked with data aggregated from insurance claims, pharmacy records, and electronic health record (EHR) data. Participants were anonymously linked between datasets by deterministic methods through a deidentification engine using encrypted tokens. Algorithms were developed and refined for identifying prostate cancer diagnoses, treatment timing, and clinical outcomes using diagnosis codes, Common Procedural Terminology codes, pharmacy codes, Systematized Medical Nomenclature for Medicine clinical terms, and unstructured text in the EHR. Data analysis was performed from January 2023 to January 2024. Exposure: Diagnosis of prostate cancer. Main Outcomes and Measures: The primary outcomes were biochemical recurrence and development of prostate cancer metastases after diagnosis or radical prostatectomy (RP). The sensitivity of the linkage and identification algorithms for clinical and administrative data were calculated relative to clinical and pathological information obtained during the GC testing process as the reference standard. Results: A total of 92 976 of 95 578 (97.2%) participants who underwent prostate GC testing were successfully linked to administrative and clinical data, including 53 871 who underwent biopsy testing and 39 105 who underwent RP testing. The median (IQR) age at GC testing was 66.4 (61.0-71.0) years. The sensitivity of the EHR linkage data for prostate cancer diagnoses was 85.0% (95% CI, 84.7%-85.2%), including 80.8% (95% CI, 80.4%-81.1%) for biopsy-tested participants and 90.8% (95% CI, 90.5%-91.0%) for RP-tested participants. Year of treatment was concordant in 97.9% (95% CI, 97.7%-98.1%) of those undergoing GC testing at RP, and 86.0% (95% CI, 85.6%-86.4%) among participants undergoing biopsy testing. The sensitivity of the linkage was 48.6% (95% CI, 48.1%-49.1%) for identifying RP and 50.1% (95% CI, 49.7%-50.5%) for identifying prostate biopsy. Conclusions and Relevance: This study established a national-scale linkage of transcriptomic and longitudinal clinical data yielding high accuracy for identifying key clinical junctures, including diagnosis, treatment, and early cancer outcome. This resource can be leveraged to enhance understandings of disease biology, patterns of care, and treatment effectiveness.

Endoscopy-assisted medial canthus incision for olfactory neuroblastoma: a case report.

Sinonasal malignant tumors are a group of uncommon malignancies that account for less than 1% of all tumors. These tumors often involve the maxillary sinus and nasal cavity, with less cumulative incidence in the ethmoidal sinus, sphenoidal sinus, and frontal sinus. The lack of consensus on the management of sinonasal malignancies is due to their rarity, diagnostic challenges, and the heterogeneity of treatments. In this paper, we present a case of endoscopic-assisted medial canthus incision combined with radiotherapy in the treatment of sinonasal malignant tumors, with the aim of providing valuable insights to clinicians on the management of these tumors.

Microbiome and metabolome analyses of milk and feces from dairy cows with healthy, subclinical, and clinical mastitis.

Mastitis is commonly recognized as a localized inflammatory udder disease induced by the infiltration of exogenous pathogens. In the present study, our objective was to discern fecal and milk variations in both microbiota composition and metabolite profiles among three distinct groups of cows: healthy cows, cows with subclinical mastitis and cows with clinical mastitis. The fecal microbial community of cows with clinical mastitis was significantly less rich and diverse than the one harbored by healthy cows. In parallel, mastitis caused a strong disturbance in milk microbiota. Metabolomic profiles showed that eleven and twenty-eight molecules exhibited significant differences among the three groups in feces and milk, respectively. Similarly, to microbiota profile, milk metabolome was affected by mastitis more extensively than fecal metabolome, with particular reference to amino acids and sugars. Pathway analysis revealed that amino acids metabolism and energy metabolism could be considered as the main pathways altered by mastitis. These findings underscore the notable distinctions of fecal and milk samples among groups, from microbiome and metabolomic points of view. This observation stands to enhance our comprehension of mastitis in dairy cows.

Study on the material basis and immunological enhancement activity of dangdi oral liquid.

Studies have shown that a lot of traditional Chinese medicines could improve the immunity of the body. Dangdi oral liquid (DDO) was mainly composed of Angelica sinensis (Oliv.) Diels (Danggui), Rehmannia glutinosa Libosch. (Dihuang), Achyranthes bidentata Bl. (Niuxi), Glycyrrhiza uralensis Fisch. (Gancao). In this study, the rapid ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method was used to identify the potentially effective compounds of DDO. Then the immune activity of DDO was measured by lymphocyte proliferation, macrophage phagocytic function, NK cell activity, delayed type hypersensitivity reaction, hemolytic plaque number, sIgA content and immune organ index. The results showed that a total of 51 compounds were identified. In addition, DDO could significantly promote the lymphocyte proliferation, improve macrophage phagocytic ability, NK cell activity, hemolytic plaque number, sIgA content and immune organ index compared with control group, and the medium dose possessed the best efficacy (P＜0.05). These results indicated that DDO could enhance the immunity of mice.

Simultaneous detection of multiple mycotoxins using MXene-based electrochemical aptasensor array and a self-developed multi-channel portable device.

In response to the pressing need for highly efficient simultaneous detection of multiple mycotoxins, which are often found co-occurring in food raw materials and feed, an MXene-based electrochemical aptasensor array (MBEAA) was developed. This aptasensor array utilizes high-specificity aptamers as recognition elements, enabling the capture of electrical signal changes in the presence of target mycotoxins. Based on this platform, a multi-channel portable electrochemical device, enabling rapid, cost-effective, and simultaneous detection of aflatoxin B1 (AFB1), ochratoxin A (OTA), and zealenone (ZEN) was further developed. The developed system boasts a wide detection range of 1.0 × 10-1 to 10.0 ng mL-1, with remarkable performance characterized by ultra-low detection limits of 41.2 pg mL-1, 27.6 pg mL-1, and 33.0 pg mL-1 for AFB1, OTA, and ZEN, respectively. Successfully applied in corn samples, this method offers a portable, easy-to-operate, and cost-effective solution for simultaneous multi-mycotoxin detection. Moreover, the application of the self-developed detection system could be expanded for simultaneous detection of many different targets when their specific aptamers or antibodies were available.

Purpurin ameliorated neuropathic allodynia and hyperalgesia by modulating neuronal mitochondrial bioenergetics and redox status in type 1 diabetic mice.

A substantial proportion of diabetic patients suffer a debilitating and persistent pain state, known as peripheral painful neuropathy that necessitates improved therapy or antidote. Purpurin, a natural anthraquinone compound from Rubia tinctorum L., has been reported to possess antidepressant activity in preclinical studies. As antidepressants have been typically used as standard agents against persistent neuropathic pain, this study aimed to probe the effect of purpurin on neuropathic pain associated with streptozotocin-induced type 1 diabetes in male C57BL6J mice. The Hargreaves test and the von Frey test were used to assess the pain-like behaviors, shown as heat hyperalgesia and mechanical allodynia respectively. Chronic treatment of diabetic mice with purpurin not only ameliorated the established symptoms of heat hyperalgesia and mechanical allodynia, but also arrested the development of these pain states given preemptively at low doses. Although purpurin treatment hardly impacted on metabolic disturbance in diabetic mice, it ameliorated exacerbated oxidative stress in pain-associated tissues, improved mitochondrial bioenergetics in dorsal root ganglion neurons and restored nerve conduction velocity in sciatic nerves. Notably, the analgesic actions of purpurin were modified by pharmacologically manipulating redox status and mitochondrial bioenergetics. These findings unveil the analgesic activity of purpurin, an effect that is causally associated with its bioenergetics-enhancing and antioxidant effects, in mice with type 1 diabetes.

Engineering carbon source division of labor for efficient α-carotene production in Corynebacterium glutamicum.

Effective utilization of glucose, xylose, and acetate, common carbon sources in lignocellulose hydrolysate, can boost biomanufacturing economics. However, carbon leaks into biomass biosynthesis pathways instead of the intended target product remain to be optimized. This study aimed to enhance α-carotene production by optimizing glucose, xylose, and acetate utilization in a high-efficiency Corynebacterium glutamicum cell factory. Heterologous xylose pathway expression in C. glutamicum resulted in strain m4, exhibiting a two-fold increase in α-carotene production from xylose compared to glucose. Xylose utilization was found to boost the biosynthesis of pyruvate and acetyl-CoA, essential precursors for carotenoid biosynthesis. Additionally, metabolic engineering including pck, pyc, ppc, and aceE deletion, completely disrupted the metabolic connection between glycolysis and the TCA cycle, further enhancing α-carotene production. This strategic intervention directed glucose and xylose primarily towards target chemical production, while acetate supplied essential metabolites for cell growth recovery. The engineered strain C. glutamicum m8 achieved 30 mg/g α-carotene, 67% higher than strain m4. In fed-batch fermentation, strain m8 produced 1802 mg/L of α-carotene, marking the highest titer reported to date in microbial fermentation. Moreover, it exhibited excellent performance in authentic lignocellulosic hydrolysate, producing 216 mg/L α-carotene, 1.45 times higher than the initial strain (m4). These labor-division strategies significantly contribute to the development of clean processes for producing various valuable chemicals from lignocellulosic resources.