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Abstract Neoadjuvant chemoimmunotherapy has emerged as a potential treatment option for resectable head and neck squamous cell carcinoma (HNSCC). In this single-arm phase II trial (NCT04826679), patients with resectable locally advanced HNSCC (T2‒T4, N0‒N3b, M0) received neoadjuvant chemoimmunotherapy with camrelizumab (200 mg), nab-paclitaxel (260 mg/m2), and cisplatin (60 mg/m2) intravenously on day one of each three-week cycle for three cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), two-year progression-free survival rate, two-year overall survival rate, and toxicities. Here, we report the perioperative outcomes; survival outcomes were not mature at the time of data analysis. Between April 19, 2021 and March 17, 2022, 48 patients were enrolled and received neoadjuvant therapy, 27 of whom proceeded to surgical resection and remaining 21 received non-surgical therapy. The ORR was 89.6% (95% CI: 80.9, 98.2) among 48 patients who completed neoadjuvant therapy. Of the 27 patients who underwent surgery, 17 (63.0%, 95% CI: 44.7, 81.2) achieved a MPR or pCR, with a pCR rate of 55.6% (95% CI: 36.8, 74.3). Treatment-related adverse events of grade 3 or 4 occurred in two patients. This study meets the primary endpoint showing potential efficacy of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin, with an acceptable safety profile, in patients with resectable locally advanced HNSCC.

Summary: Nasopharyngeal carcinoma (NPC) has high metastatic potential and is hard to detect early. This study aims to develop a deep learning model for NPC diagnosis using optical imagery. From April 2008 to May 2021, we analyzed 12,087 nasopharyngeal endoscopic images and 309 videos from 1,108 patients. The pretrained model was fine-tuned with stochastic gradient descent on the final layers. Data augmentation was applied during training. Videos were converted to images for malignancy scoring. Performance metrics like AUC, accuracy, and sensitivity were calculated based on the malignancy score. The deep learning model demonstrated high performance in identifying NPC, with AUC values of 0.981 (95% confidence of interval [CI] 0.965–0.996) for the Fujian Cancer Hospital dataset and 0.937 (0.905–0.970) for the Jiangxi Cancer Hospital dataset. The proposed model effectively diagnoses NPC with high accuracy, sensitivity, and specificity across multiple datasets. It shows promise for early NPC detection, especially in identifying latent lesions.

ObjectiveThis retrospective study analyzed the efficacy of PD-1 inhibitors combined with albumin-bound paclitaxel and cisplatin (TP regimen) in the treatment of recurrent and metastatic hypopharyngeal/laryngeal squamous cell carcinoma (RMHSCC/RMLSCC).MethodsPatients diagnosed and treated at the Sun Yat-sen University Cancer Center from August 1, 2020, to August 15, 2023, with histologically confirmed RMHSCC/RMLSCC were included. All patients received PD-1 inhibitors combined with albumin-bound paclitaxel (260mg/m2) and cisplatin (60mg/m2) for 3–4 cycles. The primary endpoints were overall survival (OS) and progression-free survival (PFS).ResultsA total of 50 patients with RMHSCC/RMLSCC who received TP+PD-1 inhibitor therapy were included, with an objective response rate (ORR) of 56.0% (28/50). The 1-year and 2-year OS rates were 80.2% (95% CI: 69.3%-92.9%) and 68.6% (95% CI: 52.6%-89.5%), respectively, while the 1-year and 2-year PFS rates were 44.7% (95% CI: 31.9%-62.5%) and 26.0% (95% CI: 12.6%-53.4%), respectively. Treatment-related adverse events mainly included rash, myelosuppression, gastrointestinal reactions, and hypothyroidism.ConclusionIn the treatment of RMHSCC/RMLSCC with TP + PD-1 inhibitors, survival rates of patients can be improved while ensuring the safety of the treatment regimen.

This study investigates the nexus between rising temperatures and household energy consumption using data from respondents' electricity bills in the ''China Residential Energy Consumption Survey.'' Our analysis reveals a significant correlation, with an 8.9 % increase in yearly energy consumption observed when the average temperature exceeds 32 °C. Additionally, we explore potential shifts in power usage due to global warming by integrating baseline estimates with daily temperature forecasts from eight contemporary climate models. Our findings project alarming trends: without interventions to curb greenhouse gas emissions, home electricity consumption could surge by 9.59–30.09 % in the medium term and by 9.77–47.70 % in the long run. By shedding light on these critical connections, our research underscores the urgent need for policy actions to mitigate the adverse impacts of climate change on energy consumption patterns.

Chronic kidney disease (CKD) is a growing global public health issue. Ginsenoside Rg1 (Rg1) has favorable nephroprotective effects, but its role and mechanism in CKD need further investigation. Therefore, we observed the effect of Rg1 on the mouse kidneys after 21 days of low-dose lipopolysaccharide (LPS) exposure. Meanwhile, we investigated the protective mechanism of Rg1 in LPS-induced mesangial cells using the Nrf2 inhibitor ML385. We found that chronic exposure to LPS caused fibrosis in mouse kidneys, accompanied by AIM2 activation and oxidative stress imbalance; however, Rg1 restored the anomalies, accompanied by activation of Nrf2/HO-1 signaling. Finally, our in vitro studies revealed that Rg1′s nephroprotective effects could be inhibited by ML385, and Rg1 can bind Nrf2, suggesting that the protective effects of Rg1 may involve Nrf2 activation and then inhibition of the AIM2. Our study has significant implications for the prevention and treatment of kidney diseases, particularly those related to inflammation.

BackgroundGraves’ disease (GD), characterized by immune aberration, is associated with gut dysbiosis. Despite the growing interest, substantial evidence detailing the precise impact of gut microbiota on GD’s autoimmune processes remains exceedingly rare.ObjectiveThis study was designed to investigate the influence of gut microbiota on immune dysregulation in GD.MethodsIt encompassed 52 GD patients and 45 healthy controls (HCs), employing flow cytometry and enzyme-linked immunosorbent assay to examine lymphocyte and cytokine profiles, alongside lipopolysaccharide (LPS) levels. Gut microbiota profiles and metabolic features were assessed using 16S rRNA gene sequencing and targeted metabolomics.ResultsOur observations revealed a disturbed B-cell distribution and elevated LPS and pro-inflammatory cytokines in GD patients compared to HCs. Significant differences in gut microbiota composition and a marked deficit in short-chain fatty acid (SCFA)-producing bacteria, including ASV263(Bacteroides), ASV1451(Dialister), and ASV503(Coprococcus), were observed in GD patients. These specific bacteria and SCFAs showed correlations with thyroid autoantibodies, B-cell subsets, and cytokine levels. In vitro studies further showed that LPS notably caused B-cell subsets imbalance, reducing conventional memory B cells while increasing naïve B cells. Additionally, acetate combined with propionate and butyrate showcased immunoregulatory functions, diminishing cytokine production in LPS-stimulated cells.ConclusionOverall, our results highlight the role of gut dysbiosis in contributing to immune dysregulation in GD by affecting lymphocyte status and cytokine production.

Abstract Studies on rodents indicate the daily oscillations of the gut microbiota have biological implications for host. However, the responses of fluctuating gut microbes to the dynamic nutrient substrates are not fully clear. In the study, we found that the feed intake, nutrient substrates, microbiota and metabolites in the colon underwent asynchronous oscillation within a day. Short-chain fatty acids (SCFAs) including acetate, propionate, butyrate and valerate peaked during T24 ~ T27 (Timepoint 24, 12:00 pm, T27, 03:00 am) whereas branched SCFAs isobutyrate and isovalerate peaked during T09 ~ T12. Further extended local similarity analysis (eLSA) revealed that the fluctuation of feed intake dynamically correlated with the colonic carbon substrates which further influenced the oscillation of sugar metabolites and acetate, propionate, butyrate and valerate with a certain time shift. The relative abundance of primary degrader Ruminococcaceae taxa was highly related to the dynamics of the carbon substrates whereas the fluctuations of secondary degraders Lactobacillaceae and Streptococcaceae taxa were highly correlated with the sugar metabolites. Meanwhile, colonic nitrogen substrates were correlated with branched amino acids and the branched SCFAs. Furthermore, we validated the evolution of gut microbes under different carbohydrate and protein combinations by using an in vitro fermentation experiment. The study pictured the dynamics of the micro-ecological environment within a day which highlights the implications of the temporal dimension in studies related to the gut microbiota. Feed intake, more precisely substrate intake, is highly correlated with microbial evolution, which makes it possible to develop chronotherapies targeting the gut microbiota through nutrition intervention.

Abstract Purpose To address the regional lymph node (RLN) distribution and the long‐term efficacy in unilateral nasopharyngeal carcinoma (NPC), providing elective irradiation for RLN with intensity‐modulated radiotherapy (IMRT). Methods The involvement of clinical data of 136 patients with unilateral NPC, who underwent IMRT from November 2003 to December 2020 were analyzed retrospectively. The therapeutic effect and failure pattern of RLN metastasis were evaluated. Results Of 57.1% patients have bilateral RLN metastasis. The rate of contralateral RLNs metastasis is lower than that of ipsilateral RLNs. Contralateral RLN metastasis mainly occurs in level VIIa (39.0%) and II (38.2%). While level IVa is only 0.7%, and none of RLN metastasis was found in level IVb and Va. The median follow‐up was 70 months, and the 3‐, 5‐and 10‐year regional recurrence‐free survival (RRFS) were 94.1%, 93.1%, and 93.1%, respectively. Conclusion Routine prophylactic irradiation may not include contralateral lower neck LN and level Va for N0‐1 unilateral NPC.

Purpose We aimed to investigate the changing trends in intentional drug poisoning among pediatric and adolescent patients over the past 10 years. Methods A retrospective study was conducted on patients younger than 20 years who visited an academic hospital emergency department (ED) in Incheon, Korea, from January 2011 through December 2020. The study focused on patients who responded with “self-harm or suicide” in the ED-based Injury In-depth Surveillance, and whose injury mechanism was drug poisoning. Exclusion criteria were unintentional injuries and the ingestion of substances other than drugs. To describe the trend over the decade, we used the number of events/100,000 ED annual visits of the database. Results A total of 3,388 cases with a median age of 17 years (interquartile range, 15-18 years) were included. The most frequently ingested drugs were acetaminophen (27.8%), followed by benzodiazepines (15.2%), antidepressants (14.1%), other sedatives and hypnotics (13.4%), and antipsychotics (8.3%). As for the events/100,000 ED annual visits, benzodiazepines showed the biggest increase, from 7.6 to 80.2 cases. Similarly, antidepressants increased from 10.2 to 71.1 cases, and antipsychotics from 3.6 to 53.7 cases. Conclusion Intentional drug poisoning has increased over the past 10 years, particularly in benzodiazepines, antidepressants, and antipsychotics. It is advisable to establish injury prevention strategies according to patients’ characteristics and ingested drugs.

Abstracts: By means of the observation of martensite, bainite and carbides, and the measurement of surface residual stress and hardness, the effect of cooling rate after isothermal stage of vacuum austempering on the microstructure and mechanical properties of M50 steel was studied. Results show that after the isothermal stage of 200 °C × 120 min, the average surface cooling rates of 4.25 °C/min, 5.69 °C/min and 7.33 °C/min were obtained when the inflation pressures of N2 were 0.05 MPa, 0.10 MPa and 0.15 MPa, and the microstructure of the austempered M50 steel was composed of lower bainite, martensite/residual austenite and carbides. When the average cooling rate was 4.25 °C/min, a large amount of lower bainite was formed in the steel, and the microstructure was significantly refined. When the average cooling rate increased to 5.69 °C/min and 7.33 °C/min, the nucleation rate of martensite increased, and the amount of martensite obtained after austempering increased. The surface residual stresses of the steel with the cooling rates of 4.25 °C/min, 5.69 °C/min and 7.33 °C/min were −54 MPa, 208 MPa and 336 MPa respectively. As the cooling rate increases, the hardness of the austempered steel increases, but that of the tempered steel decreased. This is related to the formation of more martensite and its tempering decomposition.

Microcantilever arrays are valuable tools for detecting minute physical and chemical changes. Traditional microcantilever array systems, including our previous work utilizing multiple laser arrays, frequently encounter high complexity, significant costs, and increased noise caused by laser switching. This study introduces a refraction-based laser scanning system that significantly mitigates these issues by employing a rotating glass optical block for multiplex scanning. This innovative approach not only simplifies the scanning process by eliminating the need to move the laser source or the microcantilever array but also enhances scanning speed and reduces noise, as demonstrated by our experiments. Overall, this research implements a new optical scanning strategy for microcantilever array systems, which is promising due to its direct application potential as it paves the way for more accurate, high-performing, and cost-effective sensing solutions.

In this paper, an innovative approach is introduced to address the noise issues associated with micro–cantilever array deflection measurement systems employing multiple lasers. Conventional systems are affected by laser mode hopping during switching, resulting in wavelength instability and beam spot fluctuations that take several hundred milliseconds to stabilize. To mitigate these limitations, a high–speed laser modulation technique is utilized, leveraging the averaging effect over multiple modulation cycles within the sampling window. By driving the lasers with a high–frequency carrier signal, a low–noise and stable output suitable for micro–cantilever beam deflection measurement is achieved. The effectiveness of this approach is demonstrated by simultaneously modulating the lasers and rapidly observing the spectral and centroid variations during high–speed switching using a custom–built high–speed spectrometer. The centroid fluctuations are also analyzed under different modulation frequencies. The experimental results confirm that the high–speed modulation method can reduce the standard deviation of beam spot fluctuations by more than 90%, leading to significant improvements in noise reduction compared to traditional laser switching methods. The proposed high–speed laser modulation approach offers a promising solution for enhancing the precision and stability of multi–laser micro–cantilever array deflection measurement systems.

AbstractDiabetic kidney disease (DKD) is a severe complication of type 2 diabetes mellitus (T2DM). However, the pathogenesis of DKD remains unclear, and effective treatment strategies are still lacking. Ginsenoside Rg1 (Rg1) has been reported to improve DKD, but the mechanism is unclear. NADPH oxidase 4 (NOX4) is an essential reactive oxygen species (ROS) source in the kidney. The mitogen-activated protein kinase (MAPK) signaling may exacerbate renal fibrosis. Therefore, we hypothesized that Rg1 might alleviate renal injury and fibrosis by inhibiting NOX4 and MAPK signaling in T2DM-induced DKD. We found that Rg1 significantly improves lipid deposition, fibrosis, and ROS production and reduces NOX4, p22phox, p47phox, p-ERK, p-JNK, and p-P38 MAPK expressions in the T2DM mice kidneys. We also found that the high-fat diet treatment in mice and the palmitate (PA) and PA + HG (high glucose) exposure in human mesangial cells could significantly induce lipid deposition, ROS production, fibrosis, and the activation of NOX4–MAPK signaling. The results suggest that high lipid and glucose may play a significant role in DKD progression, while Rg1 may attenuate renal fibrosis by inhibiting NOX4–MAPK signaling.

Abstract Background Isatis tinctoria Linnaeus and Isatis indigotica Fortune are very inconsistent in their morphological characteristics, but the Flora of China treats them as the same species. In this work, a new technology that differs from conventional barcodes is developed to prove that they are different species and to clarify their classification. Results and methods I. indigotica was indistinguishable from I. tinctoria when using ITS2. CPGAVAS2 was used to construct the chloroplast genomes. MAFFT and DnaSP were used to calculate nucleotide polymorphism, the chloroplast genomes of the two have high diversity in the rpl32 ~ trnL-UAG short region. When using this region as a mini barcode, it was found that there are obvious differences in the base numbers of I. tinctoria and different ploidy I. indigotica were found, but diploid and tetraploid I. indigotica had the same number of bases. Moreover, the reconstruction of the maximum likelihood (ML) tree, utilizing the mini-barcode, demonstrated that I. tinctoria and both diploid and tetraploid I. indigotica are located on distinct branches. The genome size of tetraploid I. indigotica was approximately 643.773 MB, the heterozygosity rate was approximately 0.98%, and the repeat sequence content was approximately 90.43%. This species has a highly heterozygous, extremely repetitive genome. Conclusion A new method was established to differentiate between I. indigotica and I. tinctoria. Furthermore, this approach provides a reference and basis for the directional breeding of Isatis.

Abstract Background Serotonin is an important signaling molecule that regulates secretory and sensory functions in the gut. Gut microbiota has been demonstrated to affect serotonin synthesis in rodent models. However, how gut microbes regulate intestinal serotonin production in piglets remains vague. To investigate the relationship between microbiota and serotonin specifically in the colon, microbial composition and serotonin concentration were analyzed in ileum-cannulated piglets subjected to antibiotic infusion from the ileum when comparing with saline infusion. Microbes that correlated positively with serotonin production were isolated from piglet colon and were further used to investigate the regulation mechanisms on serotonin production in IPEC-J2 and a putative enterochromaffin cell line RIN-14B cells. Results Antibiotic infusion increased quantities of Lactobacillus amylovorus (LA) that positively correlated with increased serotonin concentrations in the colon, while no effects observed for Limosilactobacillus reuteri (LR). To understand how microbes regulate serotonin, representative strains of LA, LR, and Streptococcus alactolyticus (SA, enriched in feces from prior observation) were selected for cell culture studies. Compared to the control group, LA, LR and SA supernatants significantly up-regulated tryptophan hydroxylase 1 (TPH1) expression and promoted serotonin production in IPEC-J2 cells, while in RIN-14B cells only LA exerted similar action. To investigate potential mechanisms mediated by microbe-derived molecules, microbial metabolites including lactate, acetate, glutamine, and γ-aminobutyric acid were selected for cell treatment based on computational and metabolite profiling in bacterial supernatant. Among these metabolites, acetate upregulated the expression of free fatty acid receptor 3 and TPH1 while downregulated indoleamine 2,3-dioxygenase 1. Similar effects were also recapitulated when treating the cells with AR420626, an agonist targeting free fatty acid receptor 3. Conclusions Overall, these results suggest that Lactobacillus amylovorus showed a positive correlation with serotonin production in the pig gut and exhibited a remarkable ability to regulate serotonin production in cell cultures. These findings provide evidence that microbial metabolites mediate the dialogue between microbes and host, which reveals a potential approach using microbial manipulation to regulate intestinal serotonin biosynthesis.

Cordycepin is considered a major bioactive component in Cordyceps militaris extract. This study was performed to evaluate the ameliorative effect of Cordyceps militaris extract (CME) and cordycepin (CPN) supplementation on intestinal damage in LPS-challenged piglets. The results showed that CPN or CME supplementation significantly increased the villus height (p < 0.01) and villus height/crypt depth ratio (p < 0.05) in the jejunum and ileum of piglets with LPS-induced intestinal inflammation. Meanwhile, CPN or CME supplementation alleviated oxidative stress and inflammatory responses by reducing the levels of MDA (p < 0.05) and pro-inflammatory cytokines in the serum. Additionally, supplementation with CPN or CME modulated the structure of the intestinal microbiota by enriching short-chain fatty acid-producing bacteria, and increased the level of butyrate (p < 0.05). The RNA-seq results demonstrated that CME or CPN altered the complement and coagulation-cascade-related genes (p < 0.05), including upregulating gene KLKB1 while downregulating the genes CFD, F2RL2, CFB, C4BPA, F7, C4BPB, CFH, C3 and PROS1, which regulate the complement activation involved in inflammatory and immune responses. Correlation analysis further demonstrated the potential relation between the gut microbiota and intestinal inflammation, oxidative stress, and butyrate in piglets. In conclusion, CPN or CME supplementation might inhibit LPS-induced inflammation and oxidative stress by modulating the intestinal microbiota and its metabolite butyrate in piglets.

Background: As a complication of Type II Diabetes Mellitus (T2DM), the etiology, pathogenesis, and treatment of cognitive dysfunction are still undefined. Recent studies demonstrated that Ginsenoside Rg1 (Rg1) has promising neuroprotective properties, but the effect and mechanism in diabetes-associated cognitive dysfunction (DACD) deserve further investigation. Methods: After establishing the T2DM model with a high-fat diet and STZ intraperitoneal injection, Rg1 was given for 8 weeks. The behavior alterations and neuronal lesions were judged using the open field test (OFT) and Morris water maze (MWM), as well as HE and Nissl staining. The protein or mRNA changes of NOX2, p-PLC, TRPC6, CN, NFAT1, APP, BACE1, NCSTN, and Aβ1-42 were investigated by immunoblot, immunofluorescence or qPCR. Commercial kits were used to evaluate the levels of IP3, DAG, and calcium ion (Ca2+) in brain tissues. Results: Rg1 therapy improved memory impairment and neuronal injury, decreased ROS, IP3, and DAG levels to revert Ca2+ overload, downregulated the expressions of p-PLC, TRPC6, CN, and NFAT1 nuclear translocation, and alleviated Aβ deposition in T2DM mice. In addition, Rg1 therapy elevated the expression of PSD95 and SYN in T2DM mice, which in turn improved synaptic dysfunction. Conclusions: Rg1 therapy may improve neuronal injury and DACD via mediating PLC–CN–NFAT1 signal pathway to reduce Aβ generation in T2DM mice.

Abstract Increasing evidence has shown that the NOD-like receptor protein 1 (NLRP1) inflammasome is associated with Aβ generation and deposition, which contributes to neuronal damage and neuronal-inflammation in Alzheimer's disease (AD). However, the specific mechanism of NLRP1 inflammasome in the pathogenesis of AD is still unclear. It has been reported that autophagy dysfunction can aggravate the pathological symptoms of AD and plays an important role in regulating Aβ generation and clearance. We hypothesized that NLRP1 inflammasome activation may induce autophagy dysfunction contributing to the progression of AD. In the present study, we observed the relationship between Aβ generation and NLRP1 inflammasome activation, as well as AMPK/mTOR mediated-autophagy dysfunction in WT 9-month-old (M) mice, APP/PS1 6 M and APP/PS1 9 M mice. Additionally, we further studied the effect of NLRP1 knockdown on cognitive function, Aβ generation, neuroinflammation and AMPK/mTOR mediated autophagy in APP/PS1 9 M mice. Our results indicated that NLRP1 inflammasome activation and AMPK/mTOR mediated-autophagy dysfunction are closely implicated in Aβ generation and deposition in APP/PS1 9 M mice, but not in APP/PS1 6 M mice. Meanwhile, we found that knockdown of NLRP1 significantly improved learning and memory impairments, decreased the expressions of NLRP1, ASC, caspase-1, p-NF-κB, IL-1β, APP, CTF-β, BACE1 and Aβ1-42, and decreased the level of p-AMPK, Beclin 1 and LC3 II, and increased the level of p-mTOR and P62 in APP/PS1 9 M mice. Our study suggested that inhibition of NLRP1 inflammasome activation improves AMPK/mTOR mediated-autophagy dysfunction, resulting in the decrease of Aβ generation, and NLRP1 and autophagy might be important targets to delay the progression of AD.

Abstract Background This study presents a summary of the clinical characteristics of non‐nasopharyngeal lymphoepithelial carcinoma (NNPLEC), effects of combined modality treatment and prognostic value of plasma Epstein–Barr virus (EBV) deoxyribonucleic acid (DNA) load, with the aim of providing a reference framework for optimizing treatment practices and outcomes. Methods Patients with NNPLEC treated by our center between January 2000 and December 2020 were retrospectively reviewed. Results In total, 728 patients were included. The lung was identified as the most common primary tumor site (64.0%), followed by the salivary gland (19.2%). A total of 539 (74.0%) patients underwent surgery, 459 (63.0%) received chemotherapy, and 361 (49.6%) were subjected to radiotherapy. The median follow‐up time was 45 months (range, 6–212 months) and 5‐year overall survival (OS) was 79.1%. Increased plasma EBV‐DNA load of >513.5 copies/mL was predictive of disease progression, with a specificity of 98.1% and a sensitivity of 98.9%. In multivariate Cox analysis, N stage, surgery, and radiotherapy were independent prognostic factors for both OS and PFS. Radiotherapy significantly improves OS in comparison with no radiotherapy group for salivary LEC, while surgery significantly improves OS for pulmonary LEC. Conclusion Based on our analysis, surgery and radiotherapy are associated with better OS and PFS for NNPLEC. Radiotherapy could be recommended for salivary LEC, while surgery remains the primary treatment strategy for pulmonary LEC patients. An increased plasma EBV‐DNA load of >513.5 copies/mL is strongly predictive of disease progression, supporting the importance of regular evaluation of plasma EBV‐DNA as part of the diagnostic routine.

Purpose The objective of this study was to assess the feasibility of incorporating virtual reality/augmented reality (VR/AR) programs into practical tests administered as part of the Korean Radiological Technologists Licensing Examination (KRTLE). This evaluation is grounded in a comprehensive survey that targeted enrolled students in departments of radiology across the nation. Methods In total, 682 students from radiology departments across the nation were participants in the survey. An online survey platform was used, and the questionnaire was structured into 5 distinct sections and 27 questions. A frequency analysis for each section of the survey was conducted using IBM SPSS ver. 27.0. Results Direct or indirect exposure to VR/AR content was reported by 67.7% of all respondents. Furthermore, 55.4% of the respondents expressed that VR/AR could be integrated into their classes, which signified a widespread acknowledgment of VR among the students. With regards to the integration of a VR/AR or mixed reality program into the practical tests for purposes of the KRTLE, a substantial amount of the respondents (57.3%) exhibited a positive inclination and recommended its introduction. Conclusion The application of VR/AR programs within practical tests of the KRTLE will be used as an alternative for evaluating clinical examination procedures and validating job skills.

The divertor is a key component of plasma facing components (PFCs). Its servicing lifetime under high heat flux (HHF) loadings seriously affects the operating time of the nuclear fusion reactor. Therefore, it is of great significance to study the thermomechanical behavior of the divertor and its fabricating materials under HHF loadings to optimize its design. However, it lacks benchmark measurements on the thermal deformation, strain and fractures of components under servicing conditions to validate simulations. In this paper, a thermomechanical benchmark model of a flat-type divertor mock-up is established, which is based on a series of HHF loading experiments with heat flux magnitudes of 1 ∼ 15 MW/m2. The thermomechanical measurements, including surface temperature, surface displacements and strain components, under HHF loading conditions are obtained with both infrared thermal imaging and digital image correlation (DIC) techniques. With postprocessing of decoupling thermal/mechanical strains, the cumulative equivalent mechanical strain at points of interest and thus their low cycle fatigue lifetime is evaluated according to measured data, which can be used as benchmark datasets for related numerical simulations. Several interesting findings involving heat transfer modes, thermomechanical responses and the corresponding fatigue lifetime change patterns were also discussed.

The redox potential plays a critical role in sustaining the stability of gut microbiota. This study measured the fecal redox potential in healthy and diarrheal pigs using direct and dilution methods and investigated their correlation with microbiota. The results showed that the fluctuations in the redox potential of healthy pig feces were consistent using two different methods and the two methods are equivalent based on an equivalence test. The redox potential was positively correlated with the number of fungi and negatively related to the total bacteria. The relative or absolute abundances of many bacteria at the phyla and genus levels were associated with redox potential. In diarrheal pigs, the potentiometric trends of the two methods demonstrated an opposing pattern and the correlation with total bacteria was reversed. Precipitously elevated redox potential was detected post-diarrhea using dilution methods. The absolute abundance of Escherichia-Shigella and Fuurnierella was positively correlated with redox potential, while both relative and absolute abundances of Limosilactobacillus were positively correlated. These results suggest that both methods are suitable for detecting gut redox potential in healthy pigs, while the dilution method is more suitable for diarrheal pigs. The findings on the correlation of Limosilactobacillus, Prevotella, and Escherichia-Shigella with redox potential offer novel insights for targeted modulation of intestinal health.

Traditional gravity wave drag parameterizations produce wind stresses that are insensitive to changing horizontal resolution in numerical weather prediction (NWP), partly due to the idealized elliptical assumption. This study employs the modified subgrid-scale orography scheme based on the Fourier transform into gravity wave drag scheme of the China Meteorological Administration Global Forecast System (CMA-GFS) to assess its impacts on simulating precipitation during the slow-moving period of Typhoon In-Fa after its landfall in Zhejiang Province, China. The simulation with the updated scheme can effectively reduce the accumulated precipitation bias of the control one and improve the simulation of precipitation distribution and intensity, especially in the hourly precipitation simulation. The improved scheme primarily influences the wind field of the low-level troposphere and also changes the convergence of the integrated water vapor transport and ascending motions related to the reduced precipitation biases. The modified scheme enhances the tendencies of the horizontal winds caused by the varying horizontal resolutions in the model, strengthening the sensitivity of the gravity wave drag across the horizontal scales. Results from medium-range forecasts indicate the modified scheme benefits the statistics scores of precipitation over China and also reduces root-mean-square errors of 2 m temperature and 10 m winds.

Summary: Chemotherapy remains controversial for stage II nasopharyngeal carcinoma because of its considerable prognostic heterogeneity. We aimed to develop an MRI-based deep learning model for predicting distant metastasis and assessing chemotherapy efficacy in stage II nasopharyngeal carcinoma. This multicenter retrospective study enrolled 1072 patients from three Chinese centers for training (Center 1, n = 575) and external validation (Centers 2 and 3, n = 497). The deep learning model significantly predicted the risk of distant metastases for stage II nasopharyngeal carcinoma and was validated in the external validation cohort. In addition, the deep learning model outperformed the clinical and radiomics models in terms of predictive performance. Furthermore, the deep learning model facilitates the identification of high-risk patients who could benefit from chemotherapy, providing useful additional information for individualized treatment decisions.

Abstract Background Lactic acid bacteria (LAB) participating in milk fermentation naturally release and enrich the fermented dairy product with a broad range of bioactive metabolites, which has numerous roles in the intestinal health-promoting of the consumer. However, information is lacking regarding the application prospect of LAB fermented milk in the animal industry. This study investigated the effects of lactic acid bacteria-fermented formula milk (LFM) on the growth performance, intestinal immunity, microbiota composition, and transcriptomic responses in weaned piglets. A total of 24 male weaned piglets were randomly divided into the control (CON) and LFM groups. Each group consisted of 6 replicates (cages) with 2 piglets per cage. Each piglet in the LFM group were supplemented with 80 mL LFM three times a day, while the CON group was treated with the same amount of drinking water. Results LFM significantly increased the average daily gain of piglets over the entire 14 d (P

Short-chain fatty acids (SCFA) can regulate appetite by stimulating the secretion of satiety hormones. However, the impact of short-chain fatty acid propionate on the release of gut satiety hormones and appetite regulation in pigs is not completely understood. In this study, 16 pigs were infused with saline or sodium propionate through a fistula in the caecum during a 28-day experimental period. We characterized the effects of propionate administration on peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) secretion from colonic tissue, and investigated the role of propionate infusion on the expression of appetite-related genes in the colon and hypothalamus. Further, the direct impact of propionate administration on the expression of orexigenic neuropeptide agouti-related protein (AgRP) in hypothalamic N38 cells was also examined. The results showed that intra-cecal infusion of propionate reduced the short-term feed intake (P 0.05). Propionate administration stimulated PYY and GLP-1 release from colon tissue in vivo and ex vivo (P

IntroductionStudies demonstrate that time-restricted feeding (TRF) can regulate gut microbiota composition. However, it is unclear whether TRF could affect the gut microbial rhythmicity in growing pigs. Therefore, the present study aimed to explore the effects of TRF on the dynamic fluctuation of the gut microbiota.MethodsA total of 10 healthy growing pigs equipped with T cannula were employed. Pigs were randomly allotted to the free access (FA) and the TRF groups with 5 replicates (1 pig/replicates). Pigs in the FA group were fed free access during the whole experimental period, whereas pigs in the TRF group were fed free access three times per day within limited times (7:00–8:00, 12:00–13:00, 17:00–18:00). The experiment lasted for 15 days, at 06:00 a.m. of the day 16, colonic digesta were collected at a 6-h interval for consecutive 24 h marked as T06 (06:00), T12 (12:00), T18 (18:00), T24 (24:00), T30 (06:00), respectively.ResultsResults showed that TRF altered the distribution of feed intake without changing the total feed intake within a day (p = 0.870). TRF decreased the overall concentration of colonic cellulose and altered their oscillating patterns. All alpha-diversity indexes of different time points showed significant differences regardless of feeding pattern with a trough at T18 or T24. TRF shifted the trough of the alpha-diversity index Simpson and Invsimpson. TRF lost the rhythmicity of Prevotellaceae, Ruminococcaceae, Bacteroidales_S24-7_group, and Peptococcaceae and gained the rhythmicity of Pasteurellaceae, Clostridiaceae_1, Veillonellaceae, and Peptostreptococcaceae. Also, TRF altered the interaction pattern by increasing the microbes involved in the co-occurrence network and their crosstalk, especially at T24. Interestingly, the microbial variation at T24 could largely explained by colonic substrates starch (R2 = 0.369; p = 0.001), cellulose (R2 = 0.235; p = 0.009) and NH4-N (R2 = 0.489; p = 0.001).ConclusionIn conclusion, TRF has changed the concentrates of cellulose and the relative abundance of specific microbes and certain microbial metabolites. In addition, TRF has more powerful effects on the fluctuation modes of these nutrient substrates, microbes, and metabolites by shifting their peaks or troughs. This knowledge facilitates the development of precision regulation targeting gut microbial rhythmicity.

Abstract Store-operated channels (SOCs) are highly selective Ca2+ channels that mediate Ca2+ influx in non-excitable and excitable (i.e., skeletal and cardiac muscle) cells. These channels are triggered by Ca2+ depletion of the endoplasmic reticulum and sarcoplasmic reticulum, independently of inositol 1,4,5-trisphosphate (InsP3), which is involved in cell growth, differentiation, and gene transcription. When the Ca2+ store is depleted, stromal interaction molecule1 (STIM1) as Ca2+ sensor redistributes into discrete puncta near the plasma membrane and activates the protein Ca2+ release activated Ca2+ channel protein 1 (Orai1). Accumulating evidence suggests that SOC is associated with several physiological roles in endothelial dysfunction and vascular smooth muscle proliferation that contribute to the progression of cardiovascular disease. This review mainly elaborates on the contribution of SOC in the vasculature (endothelial cells and vascular smooth muscle cells). We will further retrospect the literature implicating a critical role for these proteins in cardiovascular disease. Graphical Abstract Video Abstract

By using field-emission scanning electron microscopy, X-ray diffraction, impact and tensile-property tests, the effect of thermal treatment temperatures in stabilization treatment on the microstructure, dimensional stability and mechanical properties of M50 bearing steel was studied. Results show that the size of M50 steel decreases due to carbide precipitation at 400 °C, 420 °C, 440 °C and 480 °C, and increases due to martensite transformation at 460 °C. In the thermal treatment temperature range of 400–480 °C, the amount of secondary carbide precipitation in M50 steel increases first and then decreases with the increase of thermal treatment temperature, and the amount of carbide precipitation in the steel reaches the maximum at 460 °C. During the thermal treatment temperature range of 400–460 °C, the residual austenite gradually decomposes and decreases in quantity. However, at 480 °C, the residual austenite has relatively higher carbon content to make it more stable and less likely to decompose. At the same time, the tensile properties are slightly improved, the impact toughness decreases at 460 °C and improved under other conditions.

ABSTRACT Pectin exists in a vast range of plants and has a long history of acting as a functional food additive with potential prebiotic effects on intestinal health. However, knowledge of how pectin regulates gut microbial communities is still insufficient and limited. Here, metatranscriptome sequencing revealed that a pectin-enriched diet (PEC) decreased the abundances of fungal keystone taxa (e.g., amino acid-producing Kazachstania spp.) and their genes involved in oxidative phosphorylation, while it increased the abundance of sulfate-reducing Desulfovibrio spp., and methane-producing Methanobrevibacter spp. in colon microbiomes. Furthermore, we first confirmed that PEC decreased fecal redox potential in a fistula pig model, which could be supported by the enrichment of antioxidants (e.g., inosine) in feces. Fecal metagenome analysis disclosed that certain microbial taxa promoted inosine biosynthesis from pectin degradation, including Prevotella, which plays an essential role in pectin biodegradation. Overall, these results demonstrate that pectin decreases the redox potential in pig hindgut to modulate microbial composition and functions, and specific microorganisms generate reducing agents in the course of pectin degradation to decrease redox potential of microbial ecosystem. IMPORTANCE Collective studies indicate that pectin degradation promotes extensive microorganisms that can be involved in pectin degradation directly or indirectly, or benefit from the altered physiological conditions caused by pectin ingestions. Our study focuses on effects of pectin on gut microbial taxa and functions, as well as its interactions with altered environmental features. Our results demonstrate pectin-induced proreducing shifts on colon microbial taxa and functions, and first confirm that pectin decreases hindgut redox potential, which is an important environmental feature that can modulate microbial communities. These results infer that there is bidirectional regulation between microbiota and redox potential during pectin degradation. In general, this investigation proposes new insights into the pectin-modulating gut microbial ecosystem and also provides new perspectives for targeting modulation of gut microbiota.

Background: Although saline is commonly used during cardiopulmonary resuscitation (CPR) or post-cardiac arrest care, it has detrimental effects. This trial aimed to evaluate the efficacy of a balanced crystalloid solution (Plasma Solution-A [PS]) in out-of-hospital cardiac arrest (OHCA) patients and compare it with the efficacy of saline. Methods: A randomized, unblinded clinical trial was conducted using PS and saline for intravenous fluid administration during CPR and post-cardiac arrest care of non-traumatic OHCA patients admitted to the emergency department of a tertiary university hospital. Patients received saline (saline group) or PS (PS group) within 24 h of hospital arrival. The primary outcomes were changes in arterial pH, bicarbonate, base excess (BE), and chloride levels within 24 h. The secondary outcomes were clinical outcomes including mortality. Results: Of the 364 patients, data from 27 and 26 patients in the saline and PS groups, respectively, were analyzed. Analysis using a linear mixed model revealed a significant difference in BE change over time between the groups (treatment-by-time p = 0.044). Increase in BE and bicarbonate levels from 30 min to 2 h was significantly greater (p = 0.044 and p = 0.024, respectively) and the incidence of hyperchloremia was lower (p < 0.001) in the PS group than in the saline group. However, there was no difference in clinical outcomes. Conclusion: Use of PS for resuscitation resulted in a faster improvement in BE and bicarbonate, especially in the early phase of post-cardiac arrest care, and lower hyperchloremia incidence than the use of saline, without differences in clinical outcomes, in OHCA patients.

(1) Background: Post-cardiac arrest syndrome (PCAS) is a type of global ischemic reperfusion injury that occurs after the return of spontaneous circulation (ROSC). The procalcitonin to albumin ratio (PAR) has been studied as an independent prognostic factor of various diseases. There are no previous studies of PAR in patients with PCAS. We assessed if PAR is more effective than procalcitonin (PCT) in predicting prognosis for patients with PCAS. (2) Methods: This retrospective cohort study included a total of 187 patients with PCAS after non-traumatic out-of-hospital cardiac arrest (OHCA) between January 2016 and December 2020. Multivariate logistic regression analysis was conducted to assess the association between PAR and PCAS prognosis. The predictive performance of PAR was compared with PCT via the receiver-operating characteristic (ROC) analysis and DeLong test.; (3) Results: PAR at 24 and 48 h after hospital admission were independently associated with one-month neurological outcome (OR: 1.167, 95% CI: 1.023–1.330; OR: 1.077, 95% CI: 1.012–1.146, p < 0.05). By ROC analysis, PAR showed better performance over PCT at 48 h after admission in predicting one-month CPC (0.763 vs. 0.772, p = 0.010). (4) Conclusions: Our findings suggest that PAR at 48 h after admission is more effective in predicting a one-month neurological outcome than PCT at 48 h after admission in patients with PCAS after OHCA.

Background: Ginsenoside Rg1 (Rg1), an active ingredient in ginseng, may be a potential agent for the treatment of Alzheimer’s disease (AD). However, the protective effect of Rg1 on neurodegeneration in AD and its mechanism of action are still incompletely understood. Methods: Wild type (WT) and APP/PS1 AD mice, from 6 to 9 months old, were used in the experiment. The open field test (OFT) and Morris water maze (MWM) were used to detect behavioral changes. Neuronal damage was assessed by hematoxylin and eosin (H&E) and Nissl staining. Immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction (q-PCR) were used to examine postsynaptic density 95 (PSD95) expression, amyloid beta (Aβ) deposition, Tau and phosphorylated Tau (p-Tau) expression, reactive oxygen species (ROS) production, and NAPDH oxidase 2 (NOX2) expression. Results: Rg1 treatment for 12 weeks significantly ameliorated cognitive impairments and neuronal damage and decreased the p-Tau level, amyloid precursor protein (APP) expression, and Aβ generation in APP/PS1 mice. Meanwhile, Rg1 treatment significantly decreased the ROS level and NOX2 expression in the hippocampus and cortex of APP/PS1 mice. Conclusions: Rg1 alleviates cognitive impairments, neuronal damage, and reduce Aβ deposition by inhibiting NOX2 activation in APP/PS1 mice.

Abstract Purpose To evaluate the efficacy of concurrent chemoradiotherapy (CCRT) in subgroups of stage III nasopharyngeal carcinoma (NPC) in the context of intensity-modulated radiotherapy (IMRT). Methods A total of 272 patients with stage III NPC who underwent IMRT with or without concurrent chemotherapy were retrospectively reviewed. Clinicopathological features were evaluated by a Cox regression model to identify independent prognostic factors. Survival outcomes were assessed using the Kaplan–Meier method and log-rank test. Results The median follow-up time was 108 months. The 10-year locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 87.8%, 80.7%, 68.8%, and 74.9%, respectively. Multivariate analysis showed that the N classification was significantly associated with DMFS (hazard ratio [HR] 3.616, 95% confidence interval [CI] 1.387–9.428, P = 0.009), DFS (HR 2.417, 95% CI 1.291–4.423, P = 0.006), and OS (HR 3.024, 95% CI 1.385–6.602, P = 0.005). In patients with T1-3N2 disease, CCRT was associated with improved 10-year LRFS (89.6% vs. 65.4%, P = 0.005), DFS (71.9% vs. 39.4% P = 0.001) and OS (80.0% vs. 50.5%, P = 0.004) compared with IMRT alone. However, in patients with T3N0-1 disease, no significant survival differences were observed between patients treated with IMRT alone and CCRT (P > 0.05). Conclusions CCRT is an effective therapy in stage III NPC, especially for patients with N2 disease, but IMRT alone may be adequate for N0-1 disease. Individualized treatment strategies are essential for patients with varying disease risks.

Abstract Background Dietary fibers are widely considered to be beneficial to health as they produce nutrients through gut microbial fermentation while facilitating weight management and boosting gut health. To date, the gene expression profiles of the carbohydrate active enzymes (CAZymes) that respond to different types of fibers (raw potato starch, RPS; inulin, INU; pectin, PEC) in the gut microbes of pigs are not well understood. Therefore, we investigated the functional response of colonic microbiota to different dietary fibers in pigs through metatranscriptomic analysis. Results The results showed that the microbial composition and CAZyme structure of the three experimental groups changed significantly compared with the control group (CON). Based on a comparative analysis with the control diet, RPS increased the abundance of Parabacteroides, Ruminococcus, Faecalibacterium and Alloprevotella but decreased Sutterella; INU increased the relative abundance of Fusobacterium and Rhodococcus but decreased Bacillus; and PEC increased the relative abundance of the Streptococcus and Bacteroidetes groups but decreased Clostridium, Clostridioides, Intestinibacter, Gemmiger, Muribaculum and Vibrio. The gene expression of CAZymes GH8, GH14, GH24, GH38, GT14, GT31, GT77 and GT91 downregulated but that of GH77, GH97, GT3, GT10 and GT27 upregulated in the RPS diet group; the gene expression of AA4, AA7, GH14, GH15, GH24, GH26, GH27, GH38, GH101, GT26, GT27 and GT38 downregulated in the INU group; and the gene expression of PL4, AA1, GT32, GH18, GH37, GH101 and GH112 downregulated but that of CE14, AA3, AA12, GH5, GH102 and GH103 upregulated in the PEC group. Compared with the RPS and INU groups, the composition of colonic microbiota in the PEC group exhibited more diverse changes with the variation of CAZymes and Streptococcus as the main contributor to CBM61, which greatly promoted the digestion of pectin. Conclusion The results of this exploratory study provided a comprehensive overview of the effects of different fibers on nutrient digestibility, gut microbiota and CAZymes in pig colon, which will furnish new insights into the impacts of the use of dietary fibers on animal and human health.

Abstract Metals fluorides (MFs) are potential conversion cathodes to replace commercial intercalation cathodes. However, the application of MFs is impeded by their poor electronic/ionic conductivity and severe decomposition of electrolyte. Here, a composite cathode of FeF2 and polymer‐derived carbon (FeF2@PDC) with excellent cycling performance is reported. The composite cathode is composed of nanorod‐shaped FeF2 embedded in PDC matrix with excellent mechanical strength and electronic/ionic conductivity. The FeF2@PDC enables a reversible capacity of 500 mAh g–1 with a record long cycle lifetime of 1900 cycles. Remarkably, the FeF2@PDC can be cycled at a record rate of 60 C with a reversible capacity of 107 mAh g–1 after 500 cycles. Advanced electron microscopy reveals that the in situ formation of stable Fe3O4 layers on the surface of FeF2 prevents the electrolyte decomposition and leaching of iron (Fe), thus enhancing the cyclability. The results provide a new understanding to FeF2 electrochemistry, and a strategy to radically improve the electrochemical performance of FeF2 cathode for lithium‐ion battery applications.

Grinding aids to increase grinding efficiency in cement production are materials that can produce large amounts of high-quality cement in a short time by reducing surface energy by preventing particle agglomeration and improving fluidity. In the paper, a grinding aid using glycerol-waste antifreeze (GAP) was prepared and its effect on the grinding properties of clinker was investigated in contrast to that without the grinding aid. The results are as follows: The angle of repose of the cement powder added with GAP decreased as the grinding time increased (decreases by 3.8 when the grinding time was 60 minutes), indicating that it increased the flowability of the powder. On the contrary, when GAP was added, the residual amount of 45 µm sieve was also significantly reduced (4.6 % decrease) and the specific surface area increased (30.5 m2/kg), which resulted in an increase in the grinding efficiency. The zeta potential of the cement powder is greatly reduced, which lowers the surface tension of the cement particles. In the size range of 3 to 32 µm, it increases the particle content, makes the particle size distribution uniform, the 7d and 28d activity index of the powder is improved by 5 % and 6 %, respectively, and increases the compressive strength of the cement. In addition, it was confirmed that the performance of the TEA grinding aid and the grinding aid were similar, and were very effective in terms of economy.

Tartary buckwheat sprouts have a high nutritional value and are gluten-free, and polyphenols are their main active constituents. However, information regarding the active constituents’ difference of Tartary buckwheat sprouts grown from seeds with different morphology, at different developmental stages and environments is limited. Here, we developed a LC–MS-based targeted metabolomics approach to analyze polyphenols (46 flavonoids and 6 anthraquinones) in 40 Tartary buckwheat sprouts varieties. Both flavonoids and anthraquinones contributed to significant differences in sprouts grown from seed with different color or shape. Twenty-seven differential compounds were all at a higher level in 3-day-old sprouts, and the fold change from 3-day-old to 8-day-old sprouts was 1.42–6.64. A total of 25 differential compounds were all significantly upregulated upon UV-B radiation, especially for epicatechin. This study is valuable not only for better breeding cultivars of Tartary buckwheat sprouts, but also assessing their metabolic quality.

Droughts have damaging impacts on human society and ecological environments. Therefore, studying the impacts of climate variability and human activity on droughts has very important scientific value and social significance in order to understand drought warnings and weaken the adverse impacts of droughts. In this study, we used a combined drought index based on five Gravity Recovery and Climate Experiment (GRACE) and GRACE Follow-On solutions to characterize droughts in the Pearl River basin (PRB) and its sub-basins during 2003 and 2020. Then, we accurately quantified the impact of climate variability and human activity on droughts in the PRB and seven sub-basins by combining the hydrometeorological climate index and in situ human activity data. The results show that 14 droughts were identified in the PRB, particularly the North River basin with the most drought months (52.78%). The El Niño-Southern Oscillation and the Indian Ocean Dipole were found to have important impacts on droughts in the PRB. They affect the operation of the atmospheric circulation, as well as the East Asia summer monsoon, resulting in a decrease in precipitation in the PRB. This impact shows a significant east–west difference on the spatial scale. The middle and upper reaches of the PRB were found to be dominated by SM, while the lower reaches were found to be dominated by GW. Human activity was found to mainly exacerbate droughts in the PRB, but also plays a significant role in reducing peak magnitude. The sub-basins with a higher proportion of total water consumption experienced more droughts (more than 11), and vice versa. The Pearl River Delta showed the highest drought intensification. Reservoir storage significantly reduces the drought peak and severity, but the impact effect depends on its application and balance with the total water consumption. Our study provides a reference for analyzing the drought characteristics, causes, and impacts of sub-basins on a global scale.

Background Indigo-containing plant tissues change blue after a freezing treatment, which is accompanied by changes in indigo and its related compounds. Phaius flavus is one of the few monocot plants containing indigo. The change to blue after freezing was described to explore the biosynthesis of indigo in P. flavus. Methods In this study, we surveyed the dynamic change of P. flavus flower metabolomics and transcriptomics. Results The non-targeted metabolomics and targeted metabolomics results revealed a total of 98 different metabolites, the contents of indole, indican, indigo, and indirubin were significantly different after the change to blue from the freezing treatment. A transcriptome analysis screened ten different genes related to indigo upstream biosynthesis, including three anthranilate synthase genes, two phosphoribosyl-anthranilate isomerase genes, one indole-3-glycerolphosphate synthase gene, five tryptophan synthase genes. In addition, we further candidate 37 cytochrome P450 enzyme genes, one uridine diphosphate glucosyltransferase gene, and 24 β-D-glucosidase genes were screened that may have participated in the downstream biosynthesis of indigo. This study explained the changes of indigo-related compounds at the metabolic level and gene expression level during the process of P. flavus under freezing and provided new insights for increasing the production of indigo-related compounds in P. flavus. In addition, transcriptome sequencing provides the basis for functional verification of the indigo biosynthesis key genes in P. flavus.

Gut microbiota is generally recognized to play a crucial role in maintaining host health and metabolism. The correlation among gut microbiota, glycolipid metabolism, and metabolic diseases has been well reviewed in humans. However, the interplay between gut microbiota and host metabolism in swine remains incompletely understood. Given the limitation in conducting human experiments and the high similarity between swine and humans in terms of anatomy, physiology, polyphagy, habits, and metabolism and in terms of the composition of gut microbiota, there is a pressing need to summarize the knowledge gained regarding swine gut microbiota, its interplay with host metabolism, and the underlying mechanisms. This review aimed to outline the bidirectional regulation between gut microbiota and nutrient metabolism in swine and to emphasize the action mechanisms underlying the complex microbiome–host crosstalk via the gut microbiota–gut–brain axis. Moreover, it highlights the new advances in knowledge of the diurnal rhythmicity of gut microbiota. A better understanding of these aspects can not only shed light on healthy and efficient pork production but also promote our knowledge on the associations between gut microbiota and the microbiome–host crosstalk mechanism. More importantly, knowledge on microbiota, host health and metabolism facilitates the development of a precise intervention therapy targeting the gut microbiota.

TiB _2 /2024 aluminum matrix composites were prepared in situ from the Al–K _2 TiF _6 –KBF _4 reaction system; then, we investigated the microstructure and mechanical properties of the composites in the as-cast and extruded states. X-ray diffraction (XRD) and scanning electronic microscope (SEM) analyses showed that TiB _2 particles were successfully produced in the matrix by the in situ reactions. The optimal content of TiB _2 particles in the composites was 3 wt%; moreover, the size of α -Al grains in the microstructure of the composites with 3 wt% content was the smallest among the composites reinforced with different content of TiB _2 particles, and the TiB _2 particles showed a uniform distribution. The tensile strength and elongation of the composites (246 MPa and 9.8%, respectively) were 21.8% and 18.1% higher compared with those of the alloy matrix. When the TiB _2 particle content was 5 wt%, the cast composite exhibited the highest hardness of 113 HBW, which was 43.0% higher than that of the base alloy. Fracture analysis showed that the fracture mode changed from ductile to brittle as the mass fraction of TiB _2 in the composite increased. The mechanical properties of the 3 wt% TiB _2 /2024 aluminum matrix composite were significantly improved after hot extrusion, with tensile strength and elongation values of 375 MPa and 19.7%, respectively, which were 52.4% and 101% higher than those of the as-cast material.

Objective Alcohol consumption is associated with an increased risk of injuries. However, its effects on injury severity and mortality remain unclear. Specifically, the effects of alcohol intake on the severity of slip injuries have not been thoroughly investigated. Therefore, our study aimed to investigate the effects of alcohol intake on injury patterns and severity in patients experiencing slip injuries. Methods Emergency department surveillance data collected from 2011 to 2016 were analyzed for this study. Among patients aged 15 and older who were admitted for slip injuries, we compared the type and severity of injuries between the alcohol-intake group and the no-alcohol-intake group. Injury severity was classified as non-severe and severe based on the excess mortality ratio-adjusted injury severity score. Results In total, 227,548 (alcohol-intake, n=48,581; no-alcohol-intake, n=178,967) patients were included. After adjusting for age, time of injury, use of public ambulance, and season, multivariate logistic regression analysis showed that injuries were more likely to be severe in the alcohol-intake group than in the no-alcohol-intake group (odds ratio, 1.60; 95% confidence interval, 1.47–1.75). In addition, male gender and alcohol consumption had a greater synergistic effect on injury severity than the mere sum of each effect of these factors (odds ratio, 2.65; 95% confidence interval, 2.53–2.78). Conclusion Assessment of the patients influenced by alcohol was a challenge in the emergency department due to altered mental status. We suggest a considerate approach in testing and assessing male patients who slipped after alcohol-intake in the emergency department.

Objective No studies have evaluated the diagnostic value of ischemia-modified albumin (IMA) for the early detection of sepsis/septic shock in patients presenting to the emergency department (ED). We aimed to assess the usefulness of IMA in diagnosing sepsis/septic shock in the ED. Methods This retrospective, observational study analyzed IMA, lactate, high sensitivity C-reactive protein, and procalcitonin levels measured within 1 hour of ED arrival. Patients with suspected infection meeting at least two systemic inflammatory response syndrome criteria were included and classified into the infection, sepsis, and septic shock groups using Sepsis-3 definitions. Areas under the receiver operating characteristic curves (AUCs) with 95% confidence intervals (CIs) and multivariate logistic regression were used to determine diagnostic performance. Results This study included 300 adult patients. The AUC (95% CI) of IMA levels (cut-off ≥85.5 U/mL vs. ≥87.5 U/mL) was higher for the diagnosis of sepsis than for that of septic shock (0.729 [0.667–0.791] vs. 0.681 [0.613–0.824]) and was higher than the AUC of procalcitonin levels (cut-off ≥1.58 ng/mL, 0.678 [0.613–0.742]) for the diagnosis of sepsis. When IMA and lactate levels were combined, the AUCs were 0.815 (0.762–0.867) and 0.806 (0.754–0.858) for the diagnosis of sepsis and septic shock, respectively. IMA levels independently predicted sepsis (odds ratio, 1.05; 95% CI, 1.00–1.09; P=0.029) and septic shock (odds ratio, 1.07; 95% CI, 1.02–1.11; P=0.002). Conclusion Our findings indicate that IMA levels are a useful biomarker for diagnosing sepsis/ septic shock early, and their combination with lactate levels can enhance the predictive power for early diagnosis of sepsis/septic shock in the ED.

The primary aim of this paper was to identifying the geographical origin of tobacco leaves based on stable isotopic and mineral elemental fingerprint. We collected eighty-one tobacco leaf samples from Argentina, Brazil, Zimbabwe, the U.S., Zambia, and China. And nine mineral element contents and four strontium and lead isotope ratios of the tobacco leaves were determined by thermal ionization mass spectrometry (TIMS) and inductively coupled plasma mass spectrometry (ICP-MS). After variance and stepwise discriminant analysis, the discriminant functions of the tobacco leaf’s geographical origin were established. The results indicate that: (1) the contents of six mineral elements including Cu, Zn, Cr, Ni, Cd, and Pb, together with four strontium and lead isotope ratios containing 87Sr/86Sr, 208Pb/204Pb, 207Pb/204Pb, and 206Pb/204Pb, were significantly different among six countries. (2) Different countries presented some characteristic mineral elemental and isotopic fingerprint. The even contents of mineral elements from Zambian tobacco leaf were much lower than the other countries, among which four elements consisting of Zn, Cr, As, and Cd were not detected. The three average lead isotope ratios including 208Pb/204Pb, 207Pb/204Pb, and 206Pb/204Pb from Zimbabwe tobacco leaves were far higher than the other countries, and the range of which was unoverlapped. (3) The effective identification of the geographical origin of tobacco leaf was accomplished by Fisher stepwise discriminant analysis and the characteristic tracing elements consisted of Cu, Zn, Cr, Ni, Cd, Pb, 87Sr/86Sr, 207Pb/204Pb, and 206Pb/204Pb. Based on the established discriminant functions, the original and cross-validation accuracy towards different geographical origins of tobacco leaves were 98.8% and 95.1%, respectively. The study shows that the strontium and lead isotopic with mineral elemental fingerprints is a potential effective method to identify the geographical origin of tobacco leaves from different countries.

The multiple attribute group decision making (MAGDM) has always been a concern in the research field. In this article, we establish the interval neutrosophic TODIM method based on cumulative prospect theory (CPT-IN-TODIM) for MAGDM issue. This new developed CPTIN-TODIM method has markedly superiority in describing decision maker’s psychological states, which utilizes the weight function to adjust weighting attributes distinguishing from the classical TODIM method. Then, this new developed method has been applied to select the third-party logistics service providers and been expound on the disparity with existing methods. Finally, the results of contrastive analysis indicate that this new developed method can lead to the appropriate conclusion and sticks out the differences between alternatives to provide clearer direction. Hence, the new developed CPT-IN-TODIM method is reliable and valid. First published online 19 November 2021