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Ethnopharmacological Relevance: Type 2 diabetes mellitus (T2DM) has become a public health problem worldwide. There is growing interest in finding drugs to treat T2DM from herbal medicine. Berberidis Cortex is a traditional Tibetan herb commonly used in the treatment of T2DM, and alkaloids are its main active components. However, the anti-diabetic mechanisms of the total alkaloids of Berberidis Cortex (TBC) remain unclear., Aim of the Study: The aim of this study was to evaluate the anti-T2DM efficacy of TBC and reveal the mechanisms behind its effects., Materials and Methods: UPLC-Q-Exactive Orbitrap MS technology was employed to qualitatively identify alkaloid components in TBC. T2DM rat models were induced by high-fat diet combined with streptozotocin, and then treated with different doses of TBC (43.5, 87, 174 mg/kg/d) for 40 days. Biochemical parameters, such as fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glycated serum protein (GSP), homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), alongside H&E and PAS staining were used to evaluate the anti-diabetic activity of TBC. More importantly, metagenomics, transcriptomics, targeted metabolomics, and Western blot analysis were integrated to reveal the underlying mechanisms of TBC for T2DM treatment., Results: TBC significantly reduced the levels of FBG, OGTT, GSP, HOMA-IR, TC, TG, and LDL-C, and improved the histopathological alterations of pancreatic and liver tissues in T2D rats. It also reduced serum levels of lipopolysaccharide (LPS) and several pro-inflammatory cytokines (IL-6, IL-1β and TNF-α). Gut microbiome analysis by metagenomics proved that TBC could improve gut microbiota dysbiosis, including an increase in some beneficial bacteria (e.g., Bifidobacterium pseudolongum and Lactobacillus acidophilus) and a decrease in some harmful bacteria (e.g., Marvinbryantia and Parabacteroides). Western blot analysis found that TBC significantly up-regulated the expression of three intestinal barrier related tight junction proteins (ZO-1, occludin, and claudin-1), and effectively suppressed several key proteins in the TLR4/MyD88/NF-κB inflammatory cascade, including TLR4, MyD88 and p-NF-κB p65. Moreover, hepatic transcriptomics analysis further revealed the regulatory role of TBC on gluconeogenesis related genes, such as Pgc, and Creb1. Targeted metabolomics and Western blot analysis showed that TBC improved BAs dysregulation in T2DM rats, specifically increasing TCDCA and CA levels, thereby activating several proteins in the FXR/FGF15 signaling axis (i.e., FXR, FGF15 and FGFR4), and then decreased the expression of p-CREB1 and PGC-1α to inhibit liver gluconeogenesis., Conclusions: TBC can significantly improve hyperglycemia, insulin resistance, hyperlipidemia, and inflammation in T2DM rats. The mechanism is related to the regulation of multiple links, including improving gut microbiota dysbiosis, protecting the intestinal barrier by up-regulating the expression of three tight junction proteins, reducing inflammation by inhibiting the LPS/TLR4/MyD88/NF-κB pathway, and inhibiting liver gluconeogenesis by regulating BAs/FXR/FGF15 and CREB1/PGC-1α signaling pathways., Competing Interests: Declaration of competing interest Neither the entire manuscript nor any part of its content has been published or has been accepted elsewhere and this manuscript is not being submitted to any other journal. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Autoimmune myocarditis (AM) is characterized by an intricate inflammatory response within the myocardium. Dynamin-related protein 1 (Drp1), a pivotal modulator of mitochondrial fission, plays a role in the pathogenesis of various diseases. A myosin-induced experimental autoimmune myocarditis (EAM) mouse model was successfully established. Flow cytometry was employed to detect M1/M2-like macrophages. Mitochondrial fragmentation was assessed using Mito-Tracker Red CMXRos. Drp1 was upregulated and activated in EAM mice. Depletion of Drp1 was observed to mitigate inflammation, macrophage infiltration and M1 polarization within the cardiac tissue of EAM mice. In M1-like macrophages derived from the hearts of EAM mice, Drp1 was found to promote mitochondrial fission and diminish mitochondrial fusion. Furthermore, the depletion of Drp1 reduced the NF-κB-related pro-inflammatory response in EAM-associated M1-like macrophages. Drp1 drives mitochondrial fission in macrophages, driving their M1 polarization and the subsequent inflammatory response. Drp1 may represent an effective target for the prevention and treatment of AM., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cancer, ranked as the second leading cause of global mortality with a prevalence of 1 in 6 deaths, necessitates innovative approaches for effective treatment. Combinatorial drug therapy for cancer treatment targets several key pathways simultaneously and potentially enhances anti-cancer efficacy without intolerable side effects. However, it demands precise and accurate control of drug-dose combinations and their release. In this study, we demonstrated a selectively cross-linked hydrogel-based platform that can quantify and release drugs simultaneously for in-parallel cocktail drug screening. PDMS was used as the flow channel substrate and the poly (ethylene glycol) diacrylate (PEGDA) hydrogel array was formed by UV exposure using the photomask. Employing our platform, cocktails of anticancer drugs are precisely loaded and simultaneously released in-parallel into HCT-116 colon cancer cells, facilitating combinatorial drug screening. The integration of an artificial intelligence-based complex system response (AI-CSR) platform successfully identifies optimal drug-dose combinations from a pool of ten approved drugs. Notably, our cocktail drug chip demonstrates exceptional efficiency, screening 155 drug-dose combinations within a brief two and a half hours, a marked improvement over traditional methods. Furthermore, the device exhibits low drug consumption, requiring a mere 1 μL per patch of chip. Thus, our developed PDMS drug-loaded hydrogel platform presents a novel and expedited approach to quantifying drug concentrations, promising to be a faster, efficient and more precise approach for conducting cocktail drug screening experiments.

Background: Citrus products often suffer from delayed bitterness, which is generated from the conversion of non-bitter precursors (limonoate A-ring lactone, LARL) to limonin under the catalysis of limonin D-ring lactone hydrolase (LDLH). In this study, LDLH was isolated and purified from sweet orange seeds, and a rapid and accurate high-performance liquid chromatography method to quantify LARL was developed and applied to analyze the activity and enzymatic properties of purified LDLH., Results: Purified LDLH (25.22 U mg -1 ) showed bands of 245 kDa and 17.5 kDa molecular weights in native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate PAGE analysis respectively. After a 24 h incubation under strongly acidic (pH 3) or strongly alkaline (pH 9) conditions, LDLH still retained approximately 100% activity. Moreover, LDLH activity was not impaired by thermal treatment at 50 °C for 120 min. Enzyme inhibition assays showed that LDLH was inactivated only after ethylenediaminetetraacetic acid treatment, and other enzyme inhibitors showed no significant effect on its activity. In addition, the LDLH activity of calcium ion (Ca 2+ ) intervention was 108% of that in the blank group, and that of zinc ion (Zn 2+ ) intervention was 71%., Conclusion: LDLH purified in this study was a multimer containing 17.5 kDa monomer with a wide pH tolerance range (pH 3-9) and excellent thermal stability. Moreover, LDLH might be a metallopeptidase, and its activity was stimulated by Ca 2+ and significantly inhibited by Zn 2+ . These findings improve our understanding of LDLH and provide some important implications for reducing the bitterness in citrus products in the future. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The non-thermal and thermal effects on aroma of sea buckthorn juice have rarely been investigated. In this study, 57 odor compounds were identified in fresh sea buckthorn juice (FSBJ), high pressure processing sea buckthorn juice (HSBJ), and pasteurized sea buckthorn juice (PSBJ), including 29 esters, 8 aldehydes, 1 ketone, 5 alcohols, 5 acids, 6 terpenoids, and 3 others. Ethyl 2-methylbutanoate, ethyl 3-methylbutanoate, ethyl hexanoate, and ethyl 2-hydroxy-3-methylbutanoate with flavor dilution factors ranging from 729 to 59,049 contributed to the fruity odors of FSBJ and HSBJ. Besides, the formation of off-odor compounds including hexanal, nonanal, furfural, 3-methylbutanoic acid, and dimethyl disulfide with odor activity values ≥ 1, imparts fatty, roasted, sweaty, and cooked odor in PSBJ. The variations of vitamin C and reducing sugar are significantly associated with changes in odor-active compounds during pasteurized processing. These findings provide new insights that high pressure processing minimizes the adverse effects of pasteurization., 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 © 2024 Elsevier B.V. All rights reserved.)

Atomic Ag cluster bonding is employed to reinforce the interface between PF3T nano-cluster and TiO 2 nanoparticle. With an optimized Ag loading (Ag/TiO 2  = 0.5 wt%), the Ag atoms will uniformly disperse on TiO 2 thus generating a high density of intermediate states in the band gap to form the electron channel between the terthiophene group of PF3T and the TiO 2 in the hybrid composite (denoted as T@Ag05-P). The former expands the photon absorption band width and the latter facilitates the core-hole splitting by injecting the photon excited electron (from the excitons in PF3T) into the conduction band (CB) of TiO 2 . These characteristics enable the high efficiency of H 2 production to 16 580 µmol h -1  g -1 and photocatalysis stability without degradation under visible light exposure for 96 h. Compared to that of hybrid material without Ag bonding (TiO 2 @PF3T), the H 2 production yield and stability are improved by 4.1 and 18.2-fold which shows the best performance among existing materials in similar component combination and interfacial reinforcement. The unique bonding method offers a new prospect to accelerate the development of photocatalytic hydrogen production technologies., (© 2024 Wiley‐VCH GmbH.)

The current selection of ligands for both proteins of interest (POI) and E3 ubiquitin ligase significantly restricts the scope of targeted protein degradation (TPD) technologies. This study introduces cell-penetrating peptide-induced chimera conjugates (cp-PCCs) targeting the DHHC3 enzyme involved in PD-L1 palmitoylation. This approach disrupts PD-L1's immunosuppressive function, enhancing anti-tumor immunity. We developed cp-PCCs to degrade DHHC3, directly linking DHHC3-mediated PD-L1 palmitoylation to PD-L1 stability on tumor cells. Our research utilized both in vitro assays and in vivo experiments in immune checkpoint blockade-resistant mouse models. We focused on a CRBN-based cp-PCC named PCC16, which demonstrated a DC50 of 102 nmol for DHHC3 degradation and significantly reduced PD-L1 levels. In resistant models, PCC16 not only robustly downregulated PD-L1 but also exhibited substantial anti-tumor activity in vivo without significant toxicity. This outperformed traditional inhibitors, showcasing the potential of cp-PCC technology to bypass current PROTAC limitations. Our findings suggest that cp-PCCs offer a promising method for targeting PD-L1 through DHHC3 inhibition and support their continued exploration as a versatile tool in cancer immunotherapy, especially for tumors resistant to standard treatments., (© 2024. The Author(s).)

Background: Most breast cancer-related deaths are caused by distant metastases and drug resistance. It is important to find appropriate biomarkers to monitor the disease and to predict patient responses after treatment early and accurately. Many studies have found that clustered circulating tumor cells, with more correlations with metastatic cancer and poor survival of patients than individual ones, are promising biomarkers., Methods: Eighty samples from eleven patients with breast cancer during follow-up visits were examined. By using a microfluidic chip and imaging system, the number of circulating tumor cells and microemboli (CTC/CTM) were counted to assess the distribution in stratified patients and the potential in predicting the disease condition of patients after treatments during follow-up visits. Specific components and subtypes of CTM were also preliminarily investigated., Results: Compared to CTC, CTM displayed a distinguishable distribution in stratified patients, having a better AUC value, in predicting the disease progression of breast cancer patients during follow-up visits in this study. Four subtypes were categorized from the identified CTM by considering different components. In combination with CEA and CA153, enumerated CTC and CTM from individual patients were applied to monitor the disease condition and patient response to the therapy during follow-up visits., Conclusions: The CTM and its subtypes are promising biomarkers and valuable tools for studying cancer metastasis and longitudinally monitoring cancer patients during follow-up visits.

Background: Whey protein isolate (WPI) generally represents poor functional properties such as thermal stability, emulsifying activity and antioxidant activity near its isoelectric point or high temperatures, which limit its application in the food industry. The preparation of WPI-polysaccharide covalent conjugates based on Maillard reaction is a promising method to improve the physical and chemical stability and functional properties of WPI. In this research, WPI-inulin conjugates were prepared through wet heating method and ultrasound method and their structural and functional properties were examined., Results: In conjugates, the free amino acid content was reduced, the high molecular bands were emerged at sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), new C-N bonds were formed in Fourier-transform infrared (FTIR) spectroscopy, and fluorescence intensity was reduced compared with WPI. Furthermore, the result of circular dichroism (CD) spectroscopy also showed that the secondary structure of conjugates was changed. Conjugates with ultrasound treatment had better structural properties compared with those prepared by wet heating treatment. The functional properties such as thermal stability, emulsifying activity index (EAI), emulsion stability (ES) and antioxidant activity of conjugates with wet heating treatment were significantly improved compared with WPI. The EAI and ES of conjugates with ultrasound treatment were the highest, but the thermal stability and antioxidant activity were only close to that of the conjugates with wet heating treatment for 2 h., Conclusion: This study revealed that WPI-inulin conjugates prepared with ultrasound or wet heating method not only changed the structural characteristics of WPI but also could promote its functional properties including thermal stability, EAI, ES and antioxidant activity. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

In this study, antagonistic endophytic fungi were isolated from postharvest chestnut fruits; endophytic antagonistic fungi and their combination of inhibitory effects on the fungal pathogen Neofusicoccum parvum were evaluated. A total of 612 endophytic fungi were isolated from 300 healthy chestnut kernels, and 6 strains out of them including NS-3, NS-11, NS-38, NS-43, NS-56, and NS-58 were confirmed as antagonistic endophytic fungi against Neofusicoccum parvum ; these were separately identified as Penicillium chermesinum , Penicillium italicum , Penicillium decaturense , Penicillium oxalicum, Talarmyces siamensis , and Penicillium guanacastense . Some mixed antagonistic endophytic fungi, such as NS-3-38, NS-11-38, NS-43-56, and NS-56-58-38, exhibited a much stronger antifungal activity against N. parvum than that applied individually. Among them, the mixture of NS-3-38 showed the highest antifungal activity, and the inhibition rate was up to 86.67%. The fermentation broth of NS-3, NS-38, and their combinations exhibited an obvious antifungal activity against N. parvum , and the ethyl acetate phase extract of NS-3-38 had the strongest antifungal activity, for which the inhibitory rate was up to 90.19%. The NS-3-38 fermentation broth combined with a chitosan coating significantly reduced N. parvum incidence in chestnuts from 100% to 19%. Furthermore, the fruit decay and weight loss of chestnuts during storage were significantly decreased by the NS-3-38 fermentation broth mixture along with a chitosan coating. Therefore, a mixture of P. chermesinum and P. decaturense could be used as a potential complex biocontrol agent to control postharvest fruit decay in chestnuts.

Senescence of skeletal muscle (SkM) has been a primary contributor to senior weakness and disability in recent years. The gradually declining SkM function associated with senescence has recently been connected to an imbalance between damage and repair. Macrophages (Mac) are involved in SkM aging, and different macrophage subgroups hold different biological functions. Through comprehensive single-cell transcriptomic analysis, we first compared the metabolic pathways and biological functions of different types of cells in young (Y) and old (O) mice SkM. Strikingly, the Mac population in mice SkM was also explored, and we identified a unique Mac subgroup in O SkM characterized by highly expressed SPP1 with strong senescence and adipogenesis features. Further work was carried out on the metabolic and biological processes for these Mac subgroups. Besides, we verified that the proportion of the SPP1+ Mac was increased significantly in the quadriceps tissues of O mice, and the senotherapeutic drug combination dasatinib + quercetin (D + Q) could dramatically reduce its proportion. Our study provides novel insight into the potential role of SPP1+ Mac in SkM, which may serve as a senotherapeutic target in SkM aging., (© 2024. The Author(s).)

Aging induces a series of alterations, specifically a decline in the stature and number of villi and crypts in the small intestine, thus compromising the absorbent capability of the villi. This investigation employed a senolytic combination of dasatinib and quercetin (D+Q) to examine its impact on the intestinal tract of elderly mice. Our findings demonstrate that D+Q treatment leads to a decrease in the expression of p21, p16, and Ki67, while concurrently triggering removal of apoptotic cells within the villi. Additionally, D+Q treatment exhibits the ability to promote growth in both the height and quantity of villi and crypts, along with stimulating nitric oxide (NO) production in aged mice. The study presented a model to assess strategies to alleviate age-related senescence in the intestinal tract of elderly mice. Importantly, D+Q showcases promising potential in enhancing intestinal functionality within the aging.

Processing is an indispensable technology in the preparation of Spirulina platensis (S. platensis). The key odorants in liquids, muds, and powders from S. platensis (NM and GZ) were characterized. A total of 90 odorants were identified and 41 odorants were sniffed with the flavor dilution (FD) factors ranging from 1 to 729. Among them, nonanal, decanal, d-limonene, β-cyclocitral, and β-ionone with FD factors ≥1 were detected in S. platensis during the whole processing stages. In addition, heptanal, (E, E)-2,4-nonadienal, trans-4,5-epoxy-(E)-2-decenal, 1-hepten-3-one, isophorone, 3-ethyl-2,5-dimethylpyrazine, and α-ionone exhibited higher odor activity values in powders; β-myrcene, methional, and S-methyl methanethiosulphonate were key odorants in muds; while trans-3-penten-2-ol was key odorant in liquids. Besides, the GZ-mud presented stronger earthy and fishy odor than NM-mud. S. platensis powders have the stronger grassy odor, roasted odor, and marine odor than S. platensis muds. Overall, drying process promotes the formation of aldehydes, heterocyclic compounds, and terpenoids., 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 © 2024 Elsevier Ltd. All rights reserved.)

Objective: Develop a novel and highly efficient framework that decodes Inferior Colliculus (IC) neural activities for phoneme recognition., Methods: We propose using Hyperdimensional Computing (HDC) to support an efficient phoneme recognition algorithm, in contrast to widely applied Deep Neural Networks (DNN). The high-dimensional representation and operations in HDC are rooted in human brain functionalities and naturally parallelizable, showing the potential for efficient neural activity analysis. Our proposed method includes a spatial and temporal-aware HDC encoder that effectively captures global and local patterns. As part of our framework, we deploy the lightweight HDC-based algorithm on a highly customizable and flexible hardware platform, i.e., Field Programmable Gate Arrays (FPGA), for optimal algorithm speedup. To evaluate our method, we record IC neural activities on gerbils while playing the sound of different phonemes., Results: We compare our proposed method with multiple baseline machine learning algorithms in recognition quality and learning efficiency, across different hardware platforms. The results show that our method generally achieves better classification quality than the best-performing baseline. Compared to the Deep Residual Neural Network (i.e., ResNet), our method shows a speedup up to 74×, 67×, 210× on CPU, GPU, and FPGA respectively. We achieve up to 15% (10%) higher accuracy in consonant (vowel) classification than ResNet., Conclusion: By leveraging brain-inspired HDC for IC neural activity encoding and phoneme classification, we achieve orders of magnitude runtime speedup while improving accuracy in various challenging task settings., Significance: Decoding IC neural activities is an important step to enhance understanding about human auditory system. However, these responses from the central auditory system are noisy and contain high variance, demanding large-scale datasets and iterative model fine-tuning. The proposed HDC-based framework is more scalable and viable for future real-world deployment thanks to its fast training and overall better quality.

Lipotoxicity is a well-established phenomenon that could exacerbate damage to islet β-cells and play a significant role in the development of type 2 diabetes, the underlying mechanisms of which, however, remain unclear. In lipotoxic conditions, secretagogin (SCGN), an EF-hand calcium-binding protein abundantly expressed in islets, is found to undergo downregulation. In light of this, we aim to explore the role of SCGN in lipotoxicity-induced β-cell injury. Our findings show that exposure to ox-LDL in vitro or long-term high-fat diets (HFD) in vivo decreases SCGN expression and induces pyroptosis in β-cells. Moreover, restoring SCGN partially reverses the pyroptotic cell death under ox-LDL or HFD treatments. We have observed that the downregulation of SCGN facilitates the translocation of ChREBP from the cytosol to the nucleus, thereby promoting TXNIP transcription. The upregulation of TXNIP activates the NLRP3/Caspase-1 pathway, leading to pyroptotic cell death. In summary, our study demonstrates that lipotoxicity leads to the downregulation of SCGN expression in islet β-cells, resulting in ChREBP accumulation in the nucleus and subsequent activation of the NLRP3/Caspase-1 pyroptotic pathway. Thus, administering SCGN could be a potential therapeutic strategy to alleviate β-cell damage induced by lipotoxicity in type 2 diabetes., (© 2024. The Author(s).)

Background: Listeriosis is caused by the facultative anaerobic bacterium Listeria monocytogenes . Infection from Listeria -contaminated food or water is the main etiology. If Listeria travels outside the intestines, it can cause invasive listeriosis, such as sepsis, meningitis, and meningoencephalitis. Invasive illness is especially dangerous for pregnant women and their newborns, elderly people, and people with compromised immune systems or medical conditions such as end-stage kidney disease (ESKD) patients receiving long-term dialysis., Purpose: Describe the manifestations and hospital outcomes of invasive listeriosis and identify the risk factors for in-hospital and one-year mortality in ESKD patients receiving long-term dialysis., Patients and Methods: This retrospective observational study examined hospitalized patient records at a Taiwanese tertiary medical center from August 1, 2000, to August 31, 2021. ESKD patients on chronic dialysis were identified with invasive listeriosis by blood culture and discharge diagnosis. Over 21 years, we accurately recorded 26 cases., Results: ESKD patients on chronic dialysis with invasive listeriosis have a poor prognosis. Only 53.8% of chronic dialysis patients with invasive listeriosis survived their first hospital episode. 42.3% of hospitalized ESKD patients with invasive listeriosis survived one year later. In univariate analysis, shock, tachypnea (RR ≥ 22), respiratory failure, qSOFA score ≥ 2, and lower initial platelet count were linked to greater in-hospital mortality rates., Conclusion: ESKD patients with invasive listeriosis have a grave prognosis. Our research reveals that an early blood sample for a bacterial culture may identify invasive listeriosis in chronic dialysis patients with fever, nausea or vomiting, confusion, and respiratory distress. This study is the first to identify a lower platelet count and qSOFA score ≥ 2 as markers of high-risk invasive listeriosis in ESKD patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Liu et al.)

Chronic obstructive pulmonary disease (COPD) is one of the primary causes of mortality and morbidity worldwide. The gut microbiome, particularly the bacteriome, has been demonstrated to contribute to the progression of COPD. However, the influence of gut virome on the pathogenesis of COPD is rarely studied. Recent advances in viral metagenomics have enabled the rapid discovery of its remarkable role in COPD. In this study, deep metagenomics sequencing of fecal virus-like particles and bacterial 16S rRNA sequencing was performed on 92 subjects from China to characterize alterations of the gut virome in COPD. Lower richness and diversity of the gut virome were observed in the COPD subjects compared with the healthy individuals. Sixty-four viral species, including Clostridium phage , Myoviridae sp., and Synechococcus phage , showed positive relationships with pulmonary ventilation functions and had markedly declined population in COPD subjects. Multiple viral functions, mainly involved in bacterial susceptibility and the interaction between bacteriophages and bacterial hosts, were significantly declined in COPD. In addition, COPD was characterized by weakened viral-bacterial interactions compared with those in the healthy cohort. The gut virome showed diagnostic performance with an area under the curve (AUC) of 88.7%, which indicates the potential diagnostic value of the gut virome for COPD. These results suggest that gut virome may play an important role in the development of COPD. The information can provide a reference for the future investigation of diagnosis, treatment, and in-depth mechanism research of COPD., Importance: Previous studies showed that the bacteriome plays an important role in the progression of chronic obstructive pulmonary disease (COPD). However, little is known about the involvement of the gut virome in COPD. Our study explored the disease-specific virome signatures of patients with COPD. We found the diversity and compositions altered of the gut virome in COPD subjects compared with healthy individuals, especially those viral species positively correlated with pulmonary ventilation functions. Additionally, the declined bacterial susceptibility, the interaction between bacteriophages and bacterial hosts, and the weakened viral-bacterial interactions in COPD were observed. The findings also suggested the potential diagnostic value of the gut virome for COPD. The results highlight the significance of gut virome in COPD. The novel strategies for gut virome rectifications may help to restore the balance of gut microecology and represent promising therapeutics for COPD., Competing Interests: The authors declare no conflict of interest.

Although the telephone band (0.3-3 kHz) provides sufficient information for speech recognition, the contribution of the non-telephone band (<0.3 and >3 kHz) is unclear. To investigate its contribution, speech intelligibility and talker identification were evaluated using consonants, vowels, and sentences. The non-telephone band produced relatively good intelligibility for consonants (76.0%) and sentences (77.4%), but not vowels (11.5%). The non-telephone band supported good talker identification only with sentences (74.5%), but not vowels (45.8%) or consonants (10.8%). Furthermore, the non-telephone band cannot produce satisfactory speech intelligibility in noise at the sentence level, suggesting the importance of full-band access in realistic listening.

Introduction: Ji-Ni-De-Xie (JNDX) is a traditional herbal preparation in China. It is widely used to treat type 2 diabetes mellitus (T2DM) in traditional Tibetan medicine system. However, its antidiabetic mechanisms have not been elucidated. The aim of this study is to elucidate the underlying mechanism of JNDX on bile acids (BAs) metabolism and FXR/FGF15 signaling pathway in T2DM rats. Methods: High-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-QQQ-MS) and UPLC-Q-Exactive Orbitrap MS technology were used to identify the constituents in JNDX. High-fat diet (HFD) combined with streptozotocin (45 mg∙kg -1 ) (STZ) was used to establish a T2DM rat model, and the levels of fasting blood-glucose (FBG), glycosylated serum protein (GSP), homeostasis model assessment of insulin resistance (HOMA-IR), LPS, TNF-α, IL-1β, IL-6, TG, TC, LDL-C, HDL-C, and insulin sensitivity index (ISI) were measured to evaluate the anti-diabetic activity of JNDX. In addition, metagenomic analysis was performed to detect changes in gut microbiota. The metabolic profile of BAs was analyzed by HPLC-QQQ-MS. Moreover, the protein and mRNA expressions of FXR and FGF15 in the colon and the protein expressions of FGF15 and CYP7A1 in the liver of T2DM rats were measured by western blot and RT-qPCR. Results: A total of 12 constituents were identified by HPLC-QQQ-MS in JNDX. Furthermore, 45 chemical components in serum were identified from JNDX via UPLC-Q-Exactive Orbitrap MS technology, including 22 prototype components and 23 metabolites. Using a T2DM rat model, we found that JNDX (0.083, 0.165 and 0.33 g/kg) reduced the levels of FBG, GSP, HOMA-IR, LPS, TNF-α, IL-1β, IL-6, TG, TC, and LDL-C, and increased ISI and HDL-C levels in T2DM rats. Metagenomic results demonstrated that JNDX treatment effectively improved gut microbiota dysbiosis, including altering some bacteria (e.g., Streptococcus and Bacteroides ) associated with BAs metabolism. Additionally, JNDX improved BAs disorder in T2DM rats, especially significantly increasing cholic acid (CA) levels and decreasing ursodeoxycholic acid (UDCA) levels. Moreover, the protein and mRNA expressions of FXR and FGF15 of T2DM rats were significantly increased, while the expression of CYP7A1 protein in the liver was markedly inhibited by JNDX. Discussion: JNDX can effectively improve insulin resistance, hyperglycemia, hyperlipidemia, and inflammation in T2DM rats. The mechanism is related to its regulation of BAs metabolism and activation of FXR/FGF15 signaling pathway., 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 Tao, Peng, Wang, Sun, Ding, Xiong, Tenzin, MiMa, Nhamdriel and Fan.)

Background: Healthcare workers (HCWs) are at increased risk of contracting coronavirus disease 2019 (COVID-19) as well as worsening mental health problems and insomnia. These problems can persist for a long period, even after the pandemic. However, less is known about this topic., Aim: To analyze mental health, insomnia problems, and their influencing factors in HCWs after the COVID-19 pandemic., Methods: This multicenter cross-sectional, hospital-based study was conducted from June 1, 2023 to June 30, 2023, which was a half-year after the end of the COVID-19 emergency. Region-stratified population-based cluster sampling was applied at the provincial level for Chinese HCWs. Symptoms such as anxiety, depression, and insomnia were evaluated by the Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Insomnia Severity Index. Factors influencing the symptoms were identified by multivariable logistic regression., Results: A total of 2000 participants were invited, for a response rate of 70.6%. A total of 1412 HCWs [618 (43.8%) doctors, 583 (41.3%) nurses and 211 (14.9%) nonfrontline], 254 (18.0%), 231 (16.4%), and 289 (20.5%) had symptoms of anxiety, depression, and insomnia, respectively; severe symptoms were found in 58 (4.1%), 49 (3.5%), and 111 (7.9%) of the participants. Nurses, female sex, and hospitalization for COVID-19 were risk factors for anxiety, depression, and insomnia symptoms; moreover, death from family or friends was a risk factor for insomnia symptoms. During the COVID-19 outbreak, most [1086 (76.9%)] of the participating HCWs received psychological interventions, while nearly all [994 (70.4%)] of them had received public psychological education. Only 102 (7.2%) of the HCWs received individual counseling from COVID-19., Conclusion: Although the mental health and sleep problems of HCWs were relieved after the COVID-19 pandemic, they still faced challenges and greater risks than did the general population. Identifying risk factors would help in providing targeted interventions. In addition, although a major proportion of HCWs have received public psychological education, individual interventions are still insufficient., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The maintenance of normal vascular function and homeostasis is largely dependent on the signaling mechanisms that occur within and between cells of the vasculature. TGF-β-activated kinase 1 (TAK1), a multifaceted signaling molecule, has been shown to play critical roles in various tissue types. Although the precise function of TAK1 in the vasculature remains largely unknown, emerging evidence suggests its potential involvement in both physiological and pathological processes. A comprehensive search strategy was employed to identify relevant studies, PubMed, Web of Science, and other relevant databases were systematically searched using keywords related to TAK1, TABs and MAP3K7.In this review, we discussed the role of TAK1 in vascular signaling, with a focus on its function, activation, and related signaling pathways. Specifically, we highlight the TA1-TABs complex is a key factor, regulating vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) involved in the processes of inflammation, vascular proliferation and angiogenesis. This mini review aims to elucidate the evidence supporting TAK1 signaling in the vasculature, in order to better comprehend its beneficial and potential harmful effects upon TAK1 activation in vascular tissue., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Fan et al.)

Underwater mobile acoustic source target localization encounters several challenges, including the unknown propagation speed of the source signal, uncertainty in the observation platform's position and velocity (i.e., platform systematic errors), and economic costs. This paper proposes a new two-step closed-form localization algorithm that jointly estimates the angle of arrival (AOA), time difference of arrival (TDOA), and frequency difference of arrival (FDOA) to address these challenges. The algorithm initially introduces auxiliary variables to construct pseudo-linear equations to obtain the initial solution. It then exploits the relationship between the unknown and auxiliary variables to derive the exact solution comprising solely the unknown variables. Both theoretical analyses and simulation experiments demonstrate that the proposed method accurately estimates the position, velocity, and speed of the sound source even with an unknown sound speed and platform systematic errors. It achieves asymptotic optimality within a reasonable error range to approach the Cramér-Rao lower bound (CRLB). Furthermore, the algorithm exhibits low complexity, reduces the number of required localization platforms, and decreases the economic costs. Additionally, the simulation experiments validate the effectiveness of the proposed localization method across various scenarios, outperforming other comparative algorithms.

Ethnopharmacological Relevance: Abelmoschus manihot (L.) Medik. Seeds (AMS, སོ་མ་ར་ཛ།), a Tibetan classical herbal in China, are rich in flavonoids and phenolic glycosides compounds, such as quercetin and its derivatives. Moreover, it has been found to possess anti-rheumatoid arthritis (RA) effects. Nonetheless, its anti-RA mechanism is yet unknown., Aim of the Study: This research aimed to examine the active ingredients of AMS as well as potential pharmacological mechanisms in AMS on RA., Materials and Methods: The ultra-performance liquid chromatography-electrospray ionization-tandem multistage mass spectrometry (UPLC-ESI-IT-MS n ) technique was used to determine the primary chemical components of AMS that were responsible for the therapeutic effects on RA. In addition, 36 male Wistar rats weighing between 200 and 220 g were classified at random into six groups [normal control group, collagen-induced arthritis (CIA) group, methotrexate group (positive control, 1.05 mg/kg), AMS group (157.5 mg/kg, 315 mg/kg, 630 mg/kg)]. CIA rats were given AMS extract by intragastric administration for 28 days, and their ankles were photographed to observe the degree of swelling. Further, the arthritis score, paws swelling, and body weight changes of CIA rats were determined to observe whether AMS has any effect on RA, and synovial and cartilage tissue injuries were identified by histopathology. Besides, the levels of IL-10, TNF-α, IL-1β, INF-γ, etc. in serum were estimated by ELISA. Western blot experiments were implemented to identify the expression levels of protein involved in the JAK2/STAT3 signaling pathway in the CIA rats' synovial tissues. Moreover, the mechanisms and targets of active ingredient therapy of AMS for RA were predicted using network pharmacology and then verified using molecular docking., Result: In the present study, 12 compounds were detected by UPLC-ESI-IT-MS n , such as quercetin and its derivative which could be potential active ingredients that contribute to the anti-RA properties of AMS. Our in vivo studies on CIA rats revealed that an AMS-H dose of 630 mg/kg significantly improved joint damage while decreasing the arthritic index and paw swelling. Furthermore, AMS inhibited the INF-γ, IL-6, IL-17, IL-1β, and TNF-α, levels while upregulating the expression of anti-inflammatory cytokines IL-10 and IL-4 in serum. Besides, AMS inhibited the protein Bcl-2/Bax, STAT3, and JAK2 levels, and promoted the expression of Caspase3, SOCS1, and SOCS3 in the JAK2/STAT3 pathway. Additionally, the JAK/STAT signaling pathway was found to perform a remarkable function in the AMS therapy of RA as evidenced by enrichment in GO terms and KEGG pathways. Meanwhile, data from molecular docking experiments indicated that the core targets of PIK3CA, JAK2, and SRC bound stably to the active ingredients of mimuone, 4'-methoxy-bavachromanol, and quercetin., Conclusion: According to these findings, the AMS could improve joint inflammation in CIA rats, and its underlying mechanism could be linked to the regulation of the JAK2/STAT3 pathway. Therefore, AMS might become a promising agent for alleviating inflammation in RA patients., Competing Interests: Declaration of competing interest Neither the entire manuscript nor any part of its content has been published or has been accepted elsewhere and this manuscript is not being submitted to any other journal. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Lactic acid was formerly regarded as a byproduct of metabolism. However, extensive investigations into the intricacies of cancer development have revealed its significant contributions to tumor growth, migration, and invasion. Post-translational modifications involving lactate have been widely observed in histone and non-histone proteins, and these modifications play a crucial role in regulating gene expression by covalently attaching lactoyl groups to lysine residues in proteins. This discovery has greatly enhanced our comprehension of lactic acid's involvement in disease pathogenesis. In this article, we provide a comprehensive review of the intricate relationship between lactate and tumor immunity, the occurrence of lactylation in malignant tumors, and the exploitation of targeted lactate-lactylation in tumor immunotherapy. Additionally, we discuss future research directions, aiming to offer novel insights that could inform the investigation, diagnosis, and treatment of related diseases., 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 Zha, Zhang, Lu, Zhang, Hua, Guo, Yang and Fan.)

Debris flow is a typical natural disaster in the middle reaches of the Dadu River, Southwest China. Field physical model tests were conducted to reveal the mechanism of river blocking by debris flow in the middle reaches of the Dadu River. The dynamic processes of riHver blocking by debris flows were revealed, and based on which three typical river-blocking modes of debris flow are observed, i.e. thrust-type river blocking, mixed-flow-type river blocking and progressive river blocking. The test results showed that the material composition of debris flows plays an important role in the river-blocking mode, only the tests that adopted the mixed soil and gravel exhibited the thrust-type river blocking mode. The material composition has a controlling effect on the thrust-type river-blocking model. Mixed-flow-type river-blocking mode appears most often in the tests with an intersection angle of 60°, because the small intersection angle is conducive to the mixing of the debris flow and the water in the main channel. The debris flows composed of sand tend to block the river with mixed-flow-type river-blocking mode, accounting for 50% of the occurrences in the model tests. The high flow rate and discharge in the main channel and the low flow rate and discharge in the branch channel are the key factors controlling the progressive river-blocking mode. The test results in this study can support the debris flow disaster prevention and mitigation in this area., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Song et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Attention plays an important role in not only the awareness and perception of tinnitus but also its interactions with external sounds. Recent evidence suggests that attention is heightened in the tinnitus brain, likely as a result of relatively local cortical changes specific to deafferentation sites or global changes that help maintain normal cognitive capabilities in individuals with hearing loss. However, most electrophysiological studies have used passive listening paradigms to probe the tinnitus brain and produced mixed results in terms of finding a distinctive biomarker for tinnitus. Here, we designed a selective attention task, in which human adults attended to one of two interleaved tonal (500 Hz and 5 kHz) sequences. In total, 16 tinnitus (5 females) and 13 age- and hearing-matched control (8 females) subjects participated in the study, with the tinnitus subjects matching the tinnitus pitch to 5.4 kHz (range = 1.9-10.8 kHz). Cortical responses were recorded in both passive and attentive listening conditions, producing no differences in P1, N1, and P2 between the tinnitus and control subjects under any conditions. However, a different pattern of results emerged when the difference was examined between the attended and unattended responses. This attention-modulated cortical response was significantly greater in the tinnitus than control subjects: 3.9-times greater for N1 at 5 kHz (95% CI: 2.9 to 5.0, p = 0.007, η p 2 = 0.24) and 3.0 for P2 at 500 Hz (95% CI: 1.9 to 4.5, p = 0.026, η p 2 = 0.17). We interpreted the greater N1 modulation as local neural changes specific to the tinnitus frequency and the greater P2 as global changes to hearing loss. These two cortical measures were used to differentiate between the tinnitus and control subjects, producing 83.3% sensitivity and 76.9% specificity (AUC = 0.81, p = 0.006). These results suggest that the tinnitus brain is more plastic than that of the matched non-tinnitus controls and that the attention-modulated cortical response can be developed as a clinically meaningful biomarker for tinnitus.

As one of the most important vegetables and oils consumed globally, cruciferous foods are appreciated for their high nutritional value. However, there is no comprehensive knowledge to sufficiently unravel the "flavor mystery" of cruciferous foods. The present review provides a comprehensive literature on the recent advances regarding the contribution of glucosinolates (GSL) degradation products to cruciferous foods odor, which focuses on key GSL degradation products contributing to distinct odor of cruciferous foods ( Brassica oleracea , Brassica rapa , Brassica napus , Brassica juncea , Raphanus sativus ), and key factors affecting GSL degradation pathways (i.e., enzyme-induced degradation, thermal-induced degradation, chemical-induced degradation, microwave-induced degradation) during different processing and cooking. A total of 93 volatile GSL degradation products (i.e., 36 nitriles, 33 isothiocyanates, 3 thiocyanates, 5 epithionitriles, and 16 sulfides) and 29 GSL (i.e., 20 aliphatic, 5 aromatic, and 4 indolic) were found in generalized cruciferous foods. Remarkably, cruciferous foods have a distinctive pungent, spicy, pickled, sulfur, and vegetable odor. In general, isothiocyanates are mostly present in enzyme-induced degradation of GSL and are therefore often enriched in fresh-cut or low-temperature, short-time cooked cruciferous foods. In contrast, nitriles are mainly derived from thermal-induced degradation of GSL, and are thus often enriched in high-temperature, long-time cooked cruciferous foods.

Anisotropic structures exist in almost all living organisms to endow them with superior properties and physiological functionalities. However, conventional artificial materials possess unordered isotropic structures, resulting in limited functions and applications. The development of anisotropic structures on carbohydrates is reported to have an impact on their properties and applications. In this review, various alignment strategies for carbohydrates (i.e., cellulose, chitin and alginate) from bottom-up to top-down strategies are discussed, including the rapidly developed innovative technologies such as shear-induced orientation through extrusion-based 3D/4D printing, magnetic-assisted alignment, and electric-induced alignment. The unique properties and wide applications of anisotropic carbohydrate materials across different fields, from biomedical, biosensors, smart actuators, soft conductive materials, to thermal management are also summarized. Finally, recommendations on the selection of fabrication strategies are given. The major challenge lies in the construction of long-range hierarchical alignment with high orientation degree and precise control over complicated architectures. With the future development of hierarchical alignment strategies, alignment control techniques, and alignment mechanism elucidation, the potential of anisotropic carbohydrate materials for scalable manufacture and clinical applications will be fully realized., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Unraveling the intricacies between oxygen dynamics and cellular processes in the tumor microenvironment (TME) hinges upon precise monitoring of intracellular and intratumoral oxygen levels, which holds paramount significance. The majority of these reported oxygen nanoprobes suffer compromised lifetime and quantum yield when exposed to the robust ROS activities prevalent in TME, limiting their prolonged in vitro usability. Herein, the ruthenium-embedded oxygen nano polymeric sensor (Ru-ONPS) is proposed for precise oxygen gradient monitoring within the cellular environment and TME. Ru-ONPS (≈64±7 nm) incorporates [Ru(dpp) 3 ]Cl 2 dye into F-127 and crosslinks it with urea and paraformaldehyde, ensuring a prolonged lifetime (5.4 µs), high quantum yield (66.65 ± 2.43% in N 2 and 49.80 ± 3.14% in O 2 ), superior photostability (>30 min), and excellent stability in diverse environmental conditions. Based on the Stern-Volmer plot, the Ru-ONPS shows complete linearity for a wide dynamic range (0-23 mg L -1 ), with a detection limit of 10 µg mL -1 . Confocal imaging reveals Ru-ONPS cellular uptake and intratumoral distribution. After 72 h, HCT-8 cells show 5.20±1.03% oxygen levels, while NIH3T3 cells have 7.07±1.90%. Co-culture spheroids display declining oxygen levels of 17.90±0.88%, 10.90±0.88%, and 5.10±1.18%, at 48, 120, and 216 h, respectively. Ru-ONPS advances cellular oxygen measurement and facilitates hypoxia-dependent metastatic research and therapeutic target identification., (© 2023 Wiley‐VCH GmbH.)

Background: Bactrocera minax is a devastating pest of citrus fruits. However, there have been no effective control measures before. Few reports on the sex pheromones of B. minax are available., Results: In this study, nine of the volatile compounds in adult females were identified using headspace solid-phase microextraction (HS-SPME) in combination with gas chromatography-mass spectrometry (GC-MS). Among them, d-limonene, caprolactam, 2-Nitro-1H-imidazole, and creatinine could evoke antennal responses in males. Field bioassays showed that only d-limonene could lure male flies, with a relative lure rate of 78.18% in all tested samples, which was significantly higher than that of paraffin oil control, while all volatile compounds did not have any lure effective to female flies. Moreover, d-limonene was diluted with paraffin oil into differential concentrations, the lure effect on males was better at 100, 500, and 800 μL d-limonene mL -1 than pure d-limonene (1000 μL mL -1 ). The relative male lure rate of d-limonene at 100 μL mL -1 was 85.88%, which was significantly higher than that of food-baits (14.12%) on day 3. However, d-limonene was unattractive to female and male Bactrocera dorsalis and Zeugodacus tau. Further kinetic analysis showed that female adults released d-limonene around 15-day post eclosion. Electroantennography 1 results showed that 500 μL mL -1 d-limonene evoked the strongest responses to antennae of 10- to 25-day-old male flies., Conclusion: Our results indicated that d-limonene could be a sex pheromone from female flies of B. minax, and it could be used as a male-specific sex attractant for B. minax. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Electrochemical reduction of carbon dioxide (CO 2 ) is a promising route to up-convert this industrial byproduct. However, to perform this reaction with a small-molecule catalyst, the catalyst must be proximal to an electrode surface. Efforts to immobilize molecular catalysts on electrodes have been stymied by the need to optimize the immobilization chemistries on a case-by-case basis. Taking inspiration from nature, we applied DNA as a molecular-scale "Velcro" to investigate the tethering of three porphyrin-based catalysts to electrodes. This tethering strategy improved both the stability of the catalysts and their Faradaic efficiencies (FEs). DNA-catalyst conjugates were immobilized on screen-printed carbon and carbon paper electrodes via DNA hybridization with nearly 100% efficiency. Following immobilization, a higher catalyst stability at relevant potentials is observed. Additionally, lower overpotentials are required for the generation of carbon monoxide (CO). Finally, high FE for CO generation was observed with the DNA-immobilized catalysts as compared to the unmodified small-molecule systems, as high as 79.1% FE for CO at -0.95 V vs SHE using a DNA-tethered catalyst. This work demonstrates the potential of DNA "Velcro" as a powerful strategy for catalyst immobilization. Here, we demonstrated improved catalytic characteristics of molecular catalysts for CO 2 valorization, but this strategy is anticipated to be generalizable to any reaction that proceeds in aqueous solutions., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

High-dimensional quantum systems expand quantum channel capacity and information storage space. By implementing high-dimensional quantum logic gates, the speed of quantum computing can be practically enhanced. We propose a deterministic 4 × 4-dimensional controlled-not (CNOT) gate for a hybrid system without ancillary qudits required, where the spatial and polarization states of a single photon serve as a control qudit of four dimensions, whereas two electron-spin states in nitrogen-vacancy (NV) centers act as a four-dimensional target qudit. As the control qudits are easily operated employing simple optical elements and the target qudits are available for storage, the CNOT gate works in a deterministic way, and it can be flexibly extended to n × n-dimensional (n > 4) quantum gates for other hybrid systems or different photonic degrees of freedoms. The efficiency and fidelity of the CNOT gate are analyzed aligning with current technological capabilities, finding that they have satisfactory performances.

Introduction: Objectively predicting speech intelligibility is important in both telecommunication and human-machine interaction systems. The classic method relies on signal-to-noise ratios (SNR) to successfully predict speech intelligibility. One exception is clear speech, in which a talker intentionally articulates as if speaking to someone who has hearing loss or is from a different language background. As a result, at the same SNR, clear speech produces higher intelligibility than conversational speech. Despite numerous efforts, no objective metric can successfully predict the clear speech benefit at the sentence level., Methods: We proposed a Syllable-Rate-Adjusted-Modulation (SRAM) index to predict the intelligibility of clear and conversational speech. The SRAM used as short as 1 s speech and estimated its modulation power above the syllable rate. We compared SRAM with three reference metrics: envelope-regression-based speech transmission index (ER-STI), hearing-aid speech perception index version 2 (HASPI-v2) and short-time objective intelligibility (STOI), and five automatic speech recognition systems: Amazon Transcribe, Microsoft Azure Speech-To-Text, Google Speech-To-Text, wav2vec2 and Whisper., Results: SRAM outperformed the three reference metrics (ER-STI, HASPI-v2 and STOI) and the five automatic speech recognition systems. Additionally, we demonstrated the important role of syllable rate in predicting speech intelligibility by comparing SRAM with the total modulation power (TMP) that was not adjusted by the syllable rate., Discussion: SRAM can potentially help understand the characteristics of clear speech, screen speech materials with high intelligibility, and convert conversational speech into clear speech., 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 Yang and Zeng.)

Background: 60 Co-γ irradiation can simulate the effects of aging and enhance the flavor of distilled spirits. The present study aimed to investigate the effects of 0, 2, 4, 6, 8 and 10 kGy 60 Co-γ irradiation doses on the key aroma components in newly produced navel orange distilled spirits and thus determine the mechanism of their aging distilled spirits., Results: The identification of aroma compounds demonstrated that ethyl hexanoate, d-limonene, ethyl octanoate, 3-methyl-1-butanol and linalool are the key aroma compounds in navel orange distilled spirits, which were increased except for linalool with irradiation doses of 2-6 kGy. Irradiation treatment simulated the effects of the aging of navel orange distilled spirits by promoting the content of total acids, total esters and aldehydes. Irradiation doses of 2-6 kGy increased the aroma intensity of navel orange distilled spirits, reaching an optimum at 6 kGy. However, irradiation doses as high as 8 and 10 kGy decreased the content of esters in navel orange distilled spirits, which led to a deterioration of the spirit flavor., Conclusion: Low doses of 60 Co-γ irradiation can simulate the effects of the aging by increasing the content of key aromatic compounds in navel orange distilled spirits. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

This study explores the potential of laser-induced nano-photon-poration as a non-invasive technique for the intracellular delivery of micro/macromolecules at the single-cell level. This research proposes the utilization of gold-coated spiky polymeric nanoparticles (Au-PNPs) and gold nanorods (GNRs) to achieve efficient intracellular micro/macromolecule delivery at the single-cell level. By shifting the operating wavelength towards the near-infrared (NIR) range, the intracellular delivery efficiency and viability of Au-PNP-mediated photon-poration are compared to those using GNR-mediated intracellular delivery. Employing Au-PNPs as mediators in conjunction with nanosecond-pulsed lasers, a highly efficient intracellular delivery, while preserving high cell viability, is demonstrated. Laser pulses directed at Au-PNPs generate over a hundred hot spots per particle through plasmon resonance, facilitating the formation of photothermal vapor nanobubbles (PVNBs). These PVNBs create transient pores, enabling the gentle transfer of cargo from the extracellular to the intracellular milieu, without inducing deleterious effects in the cells. The optimization of wavelengths in the NIR region, coupled with low laser fluence (27 mJ/cm 2 ) and nanoparticle concentrations (34 µg/mL), achieves outstanding delivery efficiencies (96%) and maintains high cell viability (up to 99%) across the various cell types, including cancer and neuronal cells. Importantly, sustained high cell viability (90-95%) is observed even 48 h post laser exposure. This innovative development holds considerable promise for diverse applications, encompassing drug delivery, gene therapy, and regenerative medicine. This study underscores the efficiency and versatility of the proposed technique, positioning it as a valuable tool for advancing intracellular delivery strategies in biomedical applications.

The decoherence-free subspace (DFS) serves as a protective shield against certain types of environmental noise, allowing the system to remain coherent for extended periods of time. In this paper, we propose two protocols, i.e., one converts two-logic-qubit Knill-Laflamme-Milburn (KLM) state to two-logic-qubit Bell states, and the other converts three-logic-qubit KLM state to three-logic-qubit Greenberger-Horne-Zeilinger states, through cavity-assisted interaction in DFS. Especially, our innovative protocols achieve their objectives in a heralded way, thus enhancing experimental accessibility. Moreover, single photon detectors are incorporated into the setup, which can predict potential failures and ensure seamless interaction between the nitrogen-vacancy center and photons. Rigorous analyses and evaluations of two schemes demonstrate their abilities to achieve near-unit fidelities in principle and exceptional efficiencies. Further, our protocols offer progressive solutions to the challenges posed by decoherence, providing a pathway towards practical quantum technologies.

Endovascular therapy (EVT) is effective in the treatment of large vascular occlusive stroke. However, many factors are associated with the outcomes of acute ischemic stroke (AIS) after EVT. This study aimed to identify the main factors related to the prognosis of AIS patients after EVT. We analyzed the clinical data of AIS patients in the neurology department of our medical center from June 2017 to August 2021 following treatment with EVT. The data included the patients' blood pressure upon admission, blood glucose concentration, National Institutes of Health Stroke Scale (NIHSS) score, 90-day modified Rankin scale (mRs) score follow-up data, and time from LKN to the successful groin puncture (GP). A good outcome was defined as a 90-day mRs score of 0-2, and a poor outcome was defined as a 90-day mRs score of 3-6. A total of 144 patients were included in the study. Admission, smoking, and LKN-to-GP time, NIHSS score of 6-12 was found to be relevant to the prognosis. The results of multivariate analysis showed that prognosis was significantly influenced by baseline NIHSS (odds ratio = 3.02; 95% confidence interval, 2.878-4.252; P = 0.001), LKN-to-GP time (odds ratio = 2.17; 95% confidence interval, 1.341-2.625; P = 0.003), and time stratification (6-12 h) (odds ratio = 4.22; 95% confidence interval, 2.519-5.561; P = 0.001). Our study indicated that smoking, baseline NIHSS score, and LKN-to-GP time were the risk factors for a poor outcome in stroke patients following an EVT. Quitting smoking and shortening LKN time to GP should improve the outcome of AIS after EVT., (© 2024. The Author(s).)

As the most widespread juice produced and consumed globally, citrus juice (mandarin juice, orange juice, and grapefruit juice) is appreciated for its attractive and distinct aroma. While the decrease of characteristic aroma-active compounds and the formation of off-flavor compounds are easy to occur in processing and storage conditions. This review provides a comprehensive literature of recent research and discovery on citrus juice off-flavor, primarily focusing on off-flavor compounds induced during processing and storage (i.e., thermal, storage, light, oxygen, package, fruit maturity, diseases, centrifugal pretreatment, and debittering process), formation pathways (i.e., terpene acid-catalyzed hydration, caramelization reaction, Maillard reaction, Strecker degradation, and other oxidative degradation) of the off-flavor compounds, effective inhibitor pathway to off-flavor (i.e., electrical treatments, high pressure processing, microwave processing, ultrasound processing, and chemical treatment), as well as odor assessment techniques based on molecular sensory science. The possible precursors (terpenes, sulfur-containing amino acids, carbohydrates, carotenoids, vitamins, and phenolic acids) of citrus juice off-flavor are listed and are also proposed. This review intends to unravel the regularities of aroma variations and even off-flavor formation of citrus juice during processing and storage. Future aroma analysis techniques will evolve toward a colorimetric sensor array for odor visualization to obtain a "marker" of off-flavor in citrus juice.

Currently, the difference between key odorants of camellia oils from different processing technology (i.e., extra virgin camellia oil (EVCO), virgin camellia oil (VCO), fragrant camellia oil (FCO)) is unclear. In this study, a total of 91 odorants were identified by comprehensive two-dimensional gas chromatography and quadrupole mass spectrometry (GC × GC-qMS). The headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) provided fingerprint information for 57 odorants distinguished between EVCO, VCO, and FCO. Moreover, 76 odorants were shown flavor dilution (FD) factors range from 1 to 729, and fruity esters (ethyl 2-hydroxypropanoate, ethyl decanoate, and ethyl phenylacetate) with FD factors ≥ 27 and odor activity values ≥ 1 are the unique odorants in EVCO. (E, E)-2,4-Heptadienal, (E, E)-2,4-nonadienal, and d-limonene are the aroma-active compounds in VCO. While furfural and 3-ethyl-2,5-dimethylpyrazine with FD factors ≥ 243 are the major contributors to roasted and nutty odor in FCO. This work provides aroma markers for quality assessment of camellia oils., 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 Ltd. All rights reserved.)

Early prognosis of cancer recurrence remains difficult partially due to insufficient and ineffective screening biomarkers or regimes. This study evaluated the rare circulating tumor microemboli (CTM) from liquid biopsy individually and together with circulating tumor cells (CTCs) and serum CEA/CA19-9 in a panel, on early prediction of colorectal cancer (CRC) recurrence. Stained CTCs/CTM were detected by a microfluidic chip-based automatic rare-cell imaging platform. ROC, AUC, Kaplan-Meier survival, and Cox proportional hazard models regarding 4 selected biomarkers were analyzed. The relative risk, odds ratio, predictive accuracy, and positive/negative predictive value of biomarkers individually and in combination, to predict CRC recurrence were assessed and preliminarily validated. The EpCAM + Hochest + CD45 - CTCs/CTM could be found in all cancer stages, where more recurrences were observed in late-stage cases. Significant correlations between CTCs/CTM with metastatic stages and clinical treatment were illustrated. CA19-9 and CTM could be seen as independent risk factors in patient survivals, while stratified patients by grouped biomarkers on the Kaplan-Meier analyses presented more significant differences in predicting CRC recurrences. By monitoring the panel of selected biomarkers, disease progressions of 4 CRC patients during follow-up visits after first treatments within 3 years were predicted successfully. This study unveiled the value of rare CTM on clinical studies and a panel of selected biomarkers on predicting CRC recurrences in patients at the early time after medical treatment, in which the CTM and serum CA19-9 could be applied in clinical surveillance and CRC management to improve the accuracy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Mechanistic insight is achieved only when experiments are employed to test formal or computational models. Furthermore, in analogy to lesion studies, phantom perception may serve as a vehicle to understand the fundamental processing principles underlying healthy auditory perception. With a special focus on tinnitus-as the prime example of auditory phantom perception-we review recent work at the intersection of artificial intelligence, psychology and neuroscience. In particular, we discuss why everyone with tinnitus suffers from (at least hidden) hearing loss, but not everyone with hearing loss suffers from tinnitus. We argue that intrinsic neural noise is generated and amplified along the auditory pathway as a compensatory mechanism to restore normal hearing based on adaptive stochastic resonance. The neural noise increase can then be misinterpreted as auditory input and perceived as tinnitus. This mechanism can be formalized in the Bayesian brain framework, where the percept (posterior) assimilates a prior prediction (brain's expectations) and likelihood (bottom-up neural signal). A higher mean and lower variance (i.e. enhanced precision) of the likelihood shifts the posterior, evincing a misinterpretation of sensory evidence, which may be further confounded by plastic changes in the brain that underwrite prior predictions. Hence, two fundamental processing principles provide the most explanatory power for the emergence of auditory phantom perceptions: predictive coding as a top-down and adaptive stochastic resonance as a complementary bottom-up mechanism. We conclude that both principles also play a crucial role in healthy auditory perception. Finally, in the context of neuroscience-inspired artificial intelligence, both processing principles may serve to improve contemporary machine learning techniques., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Aim: The present study aimed to evaluate the impact of sodium-glucose cotransporter-2 inhibitors (SGLT2is) on blood lipid profile., Methods: We searched the PubMed, Cochrane Library, Medline, and EMBASE databases from the inception to July 2023 for randomized controlled trials (RCTs) comparing SGLT2i with placebo regarding lipid profile changes. The "Meta" package of R software was applied for data synthesis., Results: A total of 28 RCTs were included and 5192 patients participated in the present study, including 2686 patients who received SGLT2is intervention and 2506 patients who were in the control group. SGLT2is significantly increased blood low density lipoprotein cholesterol (LDL-C) levels [mean difference (MD): 0.09 mmol/L, 95% confidence interval (CI) (0.03, 0.16), 95% prediction interval (PI) (-0.06, 0.24), P = 0.0046] and high density lipoprotein cholesterol (HDL-C) levels [MD: 0.08 mmol/L, 95% CI (0.06, 0.11), 95% PI (-0.00, 0.17), P < 0.0001]. However, we observed neutral effect of SGLT2is on total cholesterol (TC) [MD: 0.08 mmol/L, 95% CI (-0.08, 0.24), 95% PI (-0.24, 0.40), P = 0.3150] and triglyceride (TG) [MD: -0.03 mmol/L, 95% CI (-0.23, 0.16), 95% PI (-0.70, 0.63), P = 0.7382]., Conclusion: Our study determined that SGLT2is increase both LDL-C and HDL-C levels, but exerts not significant effect on TC and TG levels., Competing Interests: Declaration of competing interest We declare that there are no conflicts of interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aging is a major risk factor for cardiovascular diseases. Our previous studies demonstrate that aging impairs the caveolar T-type Ca V 3.2-RyR axis for extracellular Ca 2+ influx to trigger Ca 2+ sparks in vascular smooth muscle cells (VSMCs). We hypothesize that the administration of senolytics, which can selectively clear senescent cells, could preserve the caveolar Ca V 3.2-RyR axis in aging VSMCs. In this study, 10-month-old mice were administered the senolytics cocktail consisting of dasatinib (5 mg/kg) and quercetin (50 mg/kg) or vehicle bi-weekly for 4 months. Using VSMCs from mouse mesenteric arteries, we found that Ca 2+ sparks were diminished after caveolae disruption by methyl-β-cyclodextrin (10 mM) in cells from D + Q treated but not vehicle-treated 14-month-old mice. D + Q treatment promoted the expression of Ca V 3.2 in 14-month-old mesenteric arteries. Structural analysis using electron tomography and immunofluorescence staining revealed the remodeling of caveolae and co-localization of Ca V 3.2-Cav-1 in D + Q treatment aged mesenteric arteries. In keeping with theoretical observations, Ca v 3.2 channel inhibition by Ni 2+ (50 μM) suppressed Ca 2+ in VSMCs from the D + Q group, with no effect observed in vehicle-treated arteries. Our study provides evidence that age-related caveolar Ca V 3.2-RyR axis malfunction can be alleviated by pharmaceutical intervention targeting cellular senescence. Our findings support the potential of senolytics for ameliorating age-associated cardiovascular disease., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Chemical fertilizers have been crucial for sustaining the current global population by supplementing overused farmland to support consistent food production, but their use is unsustainable. Pseudomonas chlororaphis is a nitrogen-fixing bacterium that could be used as a fertilizer replacement, but this microbe is delicate. It is sensitive to stressors, such as freeze-drying and high temperatures. Here, we demonstrate protection of P. chlororaphis from freeze-drying, high temperatures (50 o C), and high humidity using self-assembling metal-phenolic network (MPN) coatings. The composition of the MPN is found to significantly impact its protective efficacy, and with optimized compositions, no viability loss is observed for MPN-coated microbes under conditions where uncoated cells do not survive. Further, we demonstrate that MPN-coated microbes improve germination of seeds by 150% as compared to those treated with fresh P. chlororaphis . Taken together, these results demonstrate the protective capabilities of MPNs against environmental stressors and represent a critical step towards enabling the production and storage of delicate microbes under nonideal conditions., Competing Interests: The authors declare the following competing financial interest(s): A patent on MPNs has been filed through MIT by A.L.F., (© 2023 The Authors. Published by American Chemical Society.)

Cell patterning is a powerful technique for the precise control and arrangement of cells, enabling detailed single-cell analysis with broad applications in therapeutics, diagnostics, and regenerative medicine. This study presents a novel and efficient technique that enables massively parallel high throughput cell patterning and precise delivery of small to large biomolecules into patterned cells. The innovative cell patterning device proposed in this study is a standalone, ultrathin 3D SU-8 micro-stencil membrane, with a thickness of 10 μm. It features an array of micro-holes ranging from 40 μm to 80 μm, spaced apart by 50 μm to 150 μm. By culturing cells on top of this SU-8 membrane, the technique achieves highly efficient cell patterns varying from single-cell to cell clusters on a Petri dish. Utilizing this technique, we have achieved a remarkable reproducible patterning efficiency for mouse fibroblast L929 (80.5%), human cervical SiHa (81%), and human neuroblastoma IMR32 (89.6%) with less than 1% defects in undesired areas. Single-cell patterning efficiency was observed to be highest at 75.8% for L929 cells. Additionally, we have demonstrated massively parallel high throughput uniform transfection of large biomolecules into live patterned cells by employing an array of titanium micro-rings (10 μm outer diameter, 3 μm inner diameter) activated through infrared light pulses. Successful delivery of a wide range of small to very large biomolecules, including propidium iodide (PI) dye (668.4 Da), dextran (3 kDa), siRNA (13.3 kDa), and β-galactosidase enzyme (465 kDa), was accomplished in cell patterns for various cancer cells. Notably, our platform achieved exceptional delivery efficiencies of 97% for small molecules like PI dye and 84% for the enzyme, with corresponding high cell viability of 100% and 90%, respectively. Furthermore, the compact and reusable SU-8-based membrane device facilitates highly efficient cell patterning, transfection, and cell viability, making it a promising tool for diagnostics and therapeutic applications.

Rapid and sensitive diagnostics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of utmost importance to control the widespread coronavirus disease 2019 (COVID-19) upsurge. This study demonstrated a novel one-pot surface-enhanced Raman scattering (SERS) based immunoassay to detect SARS-CoV-2, without any washing process using a portable Raman spectrometer. The SERS-immune assay was designed using a regular digital versatile disk (DVD) substrate integrated with Raman reporter labeled silver nanoparticles for double clamping effects. The disks were molded to form nanopillar arrays and coated with silver film to enhance the sensitivity of immunoassay. The SERS platform demonstrated a limit of detection (LoD) up to 50 pg mL -1 for SARS-CoV-2 spike protein and virus-like-particle (VLP) protein in phosphate buffer saline within a turnaround time of 20 mins. Moreover, VLP protein spiked in untreated saliva achieved an LoD of 400 pg mL -1 , providing a cycle threshold (Ct) value range of 30-32, closer to reverse transcription-polymerase chain reaction (RT-PCR) results (35-40) and higher than the commercial rapid antigen tests, ranging from 25 to 28. Therefore, the developed one-pot SERS based biosensor exhibited highly sensitive and rapid detection of SARS-CoV-2, which could be a potential point-of-care platform for early and cost-effective diagnosis of the COVID-19 virus., Competing Interests: 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., (© 2023 Elsevier B.V. All rights reserved.)

Introduction: Our previous research has found that degradation of palmitoyltransferase in tumor cells using a linear peptide PROTAC leads to a significant decrease in PD-L1 expression in tumors. However, this degradation is not a sustained and efficient process. Therefore, we designed a cyclic peptide PROTAC to achieve this efficient anti-PD-L1 effect., Methods: We designed and synthesized an improvement in linear peptide PROTAC targeting palmitoyltransferase DHHC3, and used disulfide bonds to stabilize the continuous N- and C-termini of the peptides to maintain their structure. Cellular and molecular biology techniques were used to test the effect of this cyclic peptide on PD-L1., Results: In human cervical cancer cells, our cyclic peptide PROTAC can significantly downregulate palmitoyl transferase DHHC3 and PD-L1 expressions. This targeted degradation effect is enhanced with increasing doses and treatment duration, with a DC50 value much lower than that of linear peptides. Additionally, flow cytometry analysis of fluorescence intensity shows an increase in the amount of cyclic peptide entering the cell membrane with prolonged treatment time and higher concentrations. The Cellular Thermal Shift Assay (CETSA) method used in this study indicates effective binding between our novel cyclic peptide and DHHC3 protein, leading to a change in the thermal stability of the latter. The degradation of PD-L1 can be effectively blocked by the proteasome inhibitor MG132. Results from clone formation experiments illustrate that our cyclic peptide can enhance the proliferative inhibition effect of cisplatin on the C33A cell line. Furthermore, in the T cell-C33A co-culture system, cyclic peptides target the degradation of PD-L1, thereby blocking the interaction between PD-L1 and PD-1, and promoting the secretion of IFN-γ and TNF-α in the co-culture system supernatant., Conclusion: Our results demonstrate that a disulfide-bridged cyclic peptide PROTAC targeting palmitoyltransferase can provide a stable and improved anti-PD-L1 activity in human tumor cells., 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 reviewer AYX declared a shared parent affiliation with the author ML to the handling editor at the time of review., (Copyright © 2023 Shi, Dong, Fan, Dai and Liu.)

A hybrid composite of organic-inorganic semiconductor nanomaterials with atomic Au clusters at the interface decoration (denoted as PF3T@Au-TiO 2 ) is developed for visible-light-driven H 2 production via direct water splitting. With a strong electron coupling between the terthiophene groups, Au atoms and the oxygen atoms at the heterogeneous interface, significant electron injection from the PF3T to TiO 2 occurs leading to a quantum leap in the H 2 production yield (18 578 µmol g -1 h -1 ) by ≈39% as compared to that of the composite without Au decoration (PF3T@TiO 2 , 11 321 µmol g -1 h -1 ). Compared to the pure PF3T, such a result is 43-fold improved and is the best performance among all the existing hybrid materials in similar configurations. With robust process control via industrially applicable methods, it is anticipated that the findings and proposed methodologies can accelerate the development of high-performance eco-friendly photocatalytic hydrogen production technologies., (© 2023 Wiley-VCH GmbH.)