Effects of dietary metabolizable energy level on hepatic lipid metabolism and cecal microbiota in aged laying hens.

Lipid metabolic capacity, feed utilization, and the diversity of gut microbiota are reduced in the late laying stage for laying hens. This experiment aimed to investigate the effects of different levels of dietary metabolizable energy (ME) on hepatic lipid metabolism and cecal microbiota in late laying hens. The 216 Peking Pink laying hens (57-wk-old) were randomly assigned to experimental diets of 11.56 (HM = high ME), 11.14 (MM = medium ME), or 10.72 (LM = low ME) MJ of ME/kg, with each dietary treatment containing 6 replicates per group and 12 chickens per replicate. The HM group showed higher triglyceride (TG), total cholesterol (T-CHO), and low-density lipoprotein cholesterol (LDL-C) concentrations in the liver compared with the LM group; second, the HM group showed higher TG concentration and the LM group showed lower T-CHO concentration compared with MM group; finally, the HM group showed a lower hepatic lipase (HL) activity compared with the MM and LM groups (P < 0.05). There was a significant difference in the microbial community structure of the cecum between the HM and MM groups (P < 0.05). The decrease of dietary ME level resulted in a gradual decrease relative abundance of Proteobacteria. At the genus level, beneficial bacteria were significantly enriched in the LM group compared to the MM group, including Faecalibacterium, Lactobacillus, and Bifidobacterium, (linear discriminant analysis [LDA] >2, P <0.05). In addition, at the species level, Lactobacillus crispatus, Parabacteroides gordonii, Blautia caecimuris, and Lactobacillus johnsonii were significantly enriched in the LM group (LDA>2, P < 0.05). The HM group had a higher abundance of Sutterella spp. compared to the LM group (LDA>2, P <0.05). In conclusion, this research suggests that the reduction in dietary energy level did not adversely affect glycolipid metabolism or low dietary ME (10.72 MJ/kg). The findings can be helpful for maintaining intestinal homeostasis and increasing benefit for gut microbiota in late laying hens.

Winter harvesting reduces methane emissions and enhances blue carbon potential in coastal phragmites wetlands.

Enhancing the ability of coastal blue carbon to accumulate and store carbon and reduce net greenhouse gas emissions is an essential component of a comprehensive approach for tackling climate change. The annual winter harvesting of Phragmites is common worldwide. However, the effects of harvesting on methane (CH4) emissions and its potential as an effective blue carbon management strategy have rarely been reported. In this study, the effects of winter Phragmites harvesting on the CH4 and carbon dioxide (CO2) fluxes and the underlying mechanisms in coastal Phragmites wetlands were investigated by comparing the eddy covariance flux measurements for three coastal wetlands with different harvesting and tidal flow conditions. The results show that harvesting can greatly reduce the CH4 emissions and the radiative forcing of CH4 and CO2 fluxes in coastal Phragmites wetlands, suggesting that winter Phragmites harvesting has great potential as a nature-based strategy to mitigate global warming. The monthly mean CH4 fluxes were predominantly driven by air temperature, gross primary productivity, and latent heat fluxes, which are related to vegetation phenology. Additionally, variations in the salinity and water levels exerted strong regulation effects on CH4 emissions, highlighting the important role of proper tidal flow restoration and resalinization in enhancing blue carbon sequestration potential. Compared with the natural, tidally unrestricted wetlands, the CH4 fluxes in the impounded wetland were less strongly correlated with hydrometeorological variables, implying the increased difficulties of predicting CH4 variations in impounded ecosystem. This study facilitates the improved understanding of carbon exchange in coastal Phragmites wetlands with harvesting or impoundment, and provides new insights into effective blue carbon management strategies beyond tidal wetland restoration for mitigating the effects of climate change.

Observation of lymphadenopathy, systemic symptoms, and treatment in suspected indolent cutaneous B-cell lymphomas.

BACKGROUND: Following the initial diagnosis of a marginal zone or follicle center lymphoma on skin biopsy, patients undergo staging to determine the extent of disease. OBJECTIVE: We sought to characterize the frequency that these patients were found to have a systemic nodal disease upon work-up as well as the impact of imaging on disease management. METHODS: We conducted a retrospective chart review of patients presenting with a working diagnosis of PCMZL or PCFCL treated at The Ohio State University from 1990 to 2022. Data collected included: patient history, progress notes, virtual encounters, laboratory results, presentation features, imaging, and pathology. Biomarkers included ANA, SSA/SSB, BCL6 and H. Pylori labs, bone marrow biopsies, positive imaging, and need of systemic medication and mortality. RESULTS: 71 patients with suspected PCMZL and PCFCL were identified. 66 of 71 patients underwent imaging. Of this group, 12 patients (9 with suspected PCFCL and 3 with suspected PCMZL) demonstrated lymphadenopathy on imaging. Of these 12 patients, 5 underwent biopsy of suspected lymph nodes, and 3 had biopsy-proven nodal involvement and received systemic therapy. Of the remaining 7 patients with evidence of lymphadenopathy on imaging, 4 were thought to have reactive lymph nodes, and 3 were treated empirically with systemic chemotherapy due to the extent or progression of their disease. Of patients with imaging negative for lymphadenopathy, 3 of 52 (5.8%) patients with received systemic treatment, while 49 of 52 patients (94.2%) received localized treatment. LIMITATIONS: Most of the relationships between this data were correlational and patients selected for this study were limited to a single institution. CONCLUSION: Prospective study of the role of imaging without subsequent lymph biopsy to direct treatment decisions is warranted.

Exit wave reconstruction of a focal series of images with structural changes in high-resolution transmission electron microscopy.

High-resolution transmission electron microscopy (HRTEM) images can capture the atomic-resolution details of the dynamically changing structure of nanomaterials. Here, we propose a new scheme and an improved reconstruction algorithm to reconstruct the exit wave function for each image in a focal series of HRTEM images to reveal structural changes. In this scheme, the wave reconstructed from the focal series of images is treated as the initial wave in the reconstruction process for each HRTEM image. Additionally, to suppress noise at the frequencies where the signal is weak due to the modulation of the lens transfer function, a weight factor is introduced in the improved reconstruction algorithm. The advantages of the new scheme and algorithms are validated by using the HRTEM images of a natural specimen and a single-layer molybdenum disulphide. This algorithm enables image resolution enhancement and lens aberration removal, while potentially allowing the visualisation of the structural evolution of nanostructures.

A dynamic nomogram for predicting pathologic complete response to neoadjuvant chemotherapy in locally advanced rectal cancer.

AIM: To explore the clinical factors associated with pathologic complete response (pCR) for locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (nCRT) and develop a web-based dynamic nomogram. METHODS: Retrospective analysis of patients with examination confirmed LARC from 2011 to 2022. Patients from the Union Hospital of Fujian Medical University were included as the training cohort (n = 1579) and Zhangzhou Hospital of Fujian Medical University as the external validation cohort (n = 246). RESULTS: In the training cohort, after nCRT, 350 (22.2%) patients achieved pCR. More stomas were avoided in pCR patients (73.9% vs. 69.7%, p = 0.043). After a median follow-up time of 47.7 months (IQR 2-145) shown OS (5-year: 93.7% vs. 81.0%, HR = 0.310, 95%CI: 0.189-0.510, p < 0.001) and DFS (5-year: 91.2% vs. 75.0%, HR = 0.204, 95%CI: 0.216-0.484, p < 0.001) were significantly better among patients with pCR than non-pCR. Multivariable Logistic analysis shown pCR was significantly associated with Pre-CRT CEA (HR = 0.944, 95%CI: 0.921-0.968; p < 0.001), histopathology (HR = 4.608, 95%CI: 2.625-8.089; p < 0.001), Pre-CRT T stage (HR = 0.793, 95%CI: 0.634-0.993; p = 0.043), Pre-CRT N stage (HR = 0.727, 95%CI: 0.606-0.873; p = 0.001), Pre-CRT MRI EMVI (HR = 0.352, 95%CI: 0.262-0.473; p < 0.001), total neoadjuvant therapy (HR = 2.264, 95%CI: 1.280-4.004; p = 0.005). Meanwhile, the online version of the nomogram established in this study was publicized on an open-access website (URL: https://pcrpredict.shinyapps.io/LARC2/). The model predicted accuracy with a C-index of 0.73 (95% CI: 0.70-0.75), with an average C-index of 0.73 for the internal cross validation and 0.78 (95% CI: 0.72-0.83) for the external validation cohort, showing excellent model accuracy. Delong test results showed the model has an important gain value for clinical characteristics to predict pCR in rectal cancer. CONCLUSIONS: Patients with pCR had a better prognosis, including OS and DFS, and were independently associated with Pre-CRT CEA, histopathology, Pre-CRT T/N stage, Pre-CRT MRI EMVI, and TNT. A web-based dynamic nomogram was successfully established for clinical use at any time.

Optimization of off-grid renewable energy systems using a hybrid version of golden search algorithm.

Currently, the development of HRESs (hybrid renewable energy systems) in remote areas is of great importance and popularity. However, measuring and optimizing the capacity of these systems faces a difficult challenge. Multiple works had been reported in the literature to optimize such systems, all of which aim to achieve an optimal configuration with minimum annual net cost. Therefore, the significance of providing off-grid electrification to remote areas through HRESs can be highlighted as a crucial case for sustainable growth. Accordingly, the study proposes a modified metaheuristic approach, known as the Hybrid Golden Search Algorithm (HGSA), for long-term application planning and optimization of the off-grid HRES. The aim of this algorithm is to minimize the amount of net cost which is used annually; to reduce the probability of power supply interruption. In order to assess the effectiveness of the proposed algorithm, a simulation study over a long period on a remote area was conducted. From the results, increasing the reliability level from 1 % to 3 % causes a decrease in the total net annual cost by around 7.3 % under the proposed HGSA and also results in a reduction in component size (around 6 % and 21 % reductions for the wind turbine area and storage tanks, respectively). Further, the HGSA technique obtains the lowest value of fitness function for the hybrid system at a reliability level of 3 %, which is 31,539,810$. This result demonstrates that the efficiency of HGSA outperforms Fuzzy Logic and Optimization, Artificial Bee Colony (ABC), and GSA techniques. Based on this, the proposed HGSA could lead to more promising results than the other comparative algorithms. Hence, the proposed HGSA can be a valuable tool for long-term application planning and optimization of off-grid HRES, which can contribute significantly to achieving sustainable development goals.

Bio-distribution and toxicity potential of human umbilical cord mesenchymal stem cells in cynomolgus monkeys.

Mesenchymal stem cells (MSCs) have demonstrated promising advantages in the therapies of many diseases, while its multi-directional differentiation potential and immunotoxicity are the major concerns hindered their clinical translation. In this study, human umbilical Mesenchymal stem cell (hUC-MSCs) were labeled with a near-infrared fluorescent dye DiR before infused into cynomolgus monkeys, and the amount of hUC-MSCs in the peripheral blood were dynamically estimated from 5 min to 28 days post a single administration at 3 × 106 cells/kg and 2 × 107 cells/kg intravenously. As results, some hUC-MSCs distributed to the whole body within 5 min, while most of the cells accumulate in the lungs along with the systemic blood circulation, and subsequently released into the blood. The toxicity potentials of hUC-MSCs were investigated in another 30 cynomolgus monkeys, and the cells were repeatedly administrated at doses of 3 × 106 cells/kg and 2 × 107 cells/kg for 5 times on a weekly basis, with a recovery period of 1 months. hUC-MSCs showed no obvious toxic effects in cynomolgus monkeys, except xenogeneic immune rejection to human stem cells. Low levels of the hUC-MSC gene were detected in the peripheral blood of a few animals administered 2 × 107 cells/kg at 30 min subsequent to the first and last administration, and there was no significant difference in the copy number of the hUC-MSC gene in the blood samples compared with the first and last administration, indicating that the hUC-MSC was not significantly amplified in vivo, and it its safe in non-human primates. Our study for the first time verified the safety of long-term use of hUC-MSCs in primates. We have pioneered a technology for the real-time detection of hUC-MSCs in peripheral blood and provide dynamicand rapid monitoring of the distribution characteristics of hUC-MSCs in vivo. Here, we provide data supporting the application of such products for clinical treatment and the application of stem cells in major refractory diseases and regenerative medicine.

Robotic intersphincteric resection for low rectal cancer: a cumulative sum analysis for the learning curve.

PURPOSE: This study aimed to assess the learning curve of robot-assisted intersphincteric resection for low rectal cancer. METHODS: We retrospectively analyzed the clinical data of 89 patients who underwent robot-assisted intersphincteric resection. All surgeries were performed by the same group of surgeons at our institution between June 2016 and April 2021. The learning curve was evaluated using a cumulative sum analysis and the best-fit curve. The different stages of the learning curve were compared based on patient characteristics and short-term clinical outcomes to evaluate their impact on clinical efficacy. RESULTS: The minimum number of cases required to overcome the learning curve was 47. The learning curve was divided into the learning improvement and proficiency stages. Significant differences were observed in the operation time and the number of lymph nodes between the two stages (P < 0.05), whereas no significant differences were found in intraoperative blood loss, first postoperative exhaust time, postoperative complications, 3-year progression-free survival, overall survival, and local recurrence-free survival (P > 0.05). CONCLUSION: Robotic-assisted intersphincteric resection for low rectal cancer exhibits a learning curve that can be divided into two stages: namely, learning improvement and proficiency. Achieving proficiency requires a minimum of 47 surgical cases.

A feasibility study to predict 3D dose delivery accuracy for IMRT using DenseNet with log files.

OBJECTIVE: This study aims to explore the feasibility of DenseNet in the establishment of a three-dimensional (3D) gamma prediction model of IMRT based on the actual parameters recorded in the log files during delivery. METHODS: A total of 55 IMRT plans (including 367 fields) were randomly selected. The gamma analysis was performed using gamma criteria of 3% /3 mm (Dose Difference/Distance to Agreement), 3% /2 mm, 2% /3 mm, and 2% /2 mm with a 10% dose threshold. In addition, the log files that recorded the gantry angle, monitor units (MU), multi-leaf collimator (MLC), and jaws position during delivery were collected. These log files were then converted to MU-weighted fluence maps as the input of DenseNet, gamma passing rates (GPRs) under four different gamma criteria as the output, and mean square errors (MSEs) as the loss function of this model. RESULTS: Under different gamma criteria, the accuracy of a 3D GPR prediction model decreased with the implementation of stricter gamma criteria. In the test set, the mean absolute error (MAE) of the prediction model under the gamma criteria of 3% /3 mm, 2% /3 mm, 3% /2 mm, and 2% /2 mm was 1.41, 1.44, 3.29, and 3.54, respectively; the root mean square error (RMSE) was 1.91, 1.85, 4.27, and 4.40, respectively; the Sr was 0.487, 0.554, 0.573, and 0.506, respectively. There was a correlation between predicted and measured GPRs (P <  0.01). Additionally, there was no significant difference in the accuracy between the validation set and the test set. The accuracy in the high GPR group was high, and the MAE in the high GPR group was smaller than that in the low GPR group under four different gamma criteria. CONCLUSIONS: In this study, a 3D GPR prediction model of patient-specific QA using DenseNet was established based on log files. As an auxiliary tool for 3D dose verification in IMRT, this model is expected to improve the accuracy and efficiency of dose validation.

Increase in HIV reservoir and T cell immune response after CoronaVac vaccination in people living with HIV.

Introduction: CoronaVac, an inactivated vaccine developed by Sinovac Life Sciences, has been widely used for protection against Coronavirus Disease 2019 (COVID-19). This study investigates its effect on the HIV reservoir and T cell repertoires in people living with HIV (PLWHs). Methods: Blood samples were collected from fifteen PLWHs who were administered at least two doses of CoronaVac between April 2021 and February 2022. The levels of cell-associated HIV RNA (CA HIV RNA) and HIV DNA, as well as the T cell receptor (TCR) repertoire profiles, TCR clustering and TCRß annotation, were studied. Results: A significant increase was observed in CA HIV RNA at 2 weeks (431.5 ± 164.2 copies/106 cells, P = 0.039) and 12 weeks (330.2 ± 105.9 copies/106 cells, P = 0.019) after the second dose, when compared to the baseline (0 weeks) (73.6 ± 23.7 copies/106 cells). Various diversity indices of the TCRß repertoire, including Shannon index, Pielou's evenness index, and Hvj Index, revealed a slight increase (P < 0.05) following CoronaVac vaccination. The proportion of overlapping TCRß clonotypes increased from baseline (31.9 %) to 2 weeks (32.5 %) and 12 weeks (40.4 %) after the second dose. We also found that the breadth and depth of COVID-19-specific T cells increased from baseline (0.003 and 0.0035) to 12 weeks (0.0066 and 0.0058) post the second dose. Conclusions: Our study demonstrated an initial increase in HIV reservoir and TCR repertoire diversity, as well as an expansion in the depth and breadth of COVID-19-specific T-cell clones among CoronaVac-vaccinated PLWHs. These findings provide important insights into the effects of COVID-19 vaccination in PLWHs.

Substrate-Controlled Divergent Synthesis of Benzimidazole-Fused Quinolines and Spirocyclic Benzimidazole-Fused Isoindoles.

A Rh(III)-catalyzed annulation of 2-arylbenzimidazoles with α-diazo carbonyl compounds via C-H activation/carbene insertion/intramolecular cyclization is explored. The switchable product selectivity is achieved by the use of distinct α-diazo carbonyl compounds. Benzimidazole-fused quinolines are obtained through [4 + 2] annulation exclusively when 2-diazocyclohexane-1,3-diones are used, where they act as a C2 synthon. Alternatively, diazonaphthalen-1(2H)-ones merely function as a one-carbon unit synthon to generate a quaternary center through [4 + 1] cyclization to afford spirocyclic benzimidazole-fused isoindole naphthalen-2-ones. A thorough mechanistic study reveals the course of the reaction.

Mesenchymal stem cells derived from adipose tissue and umbilical cord reveal comparable efficacy upon radiation-induced colorectal fibrosis in rats.

Chemoradiotherapy (CRT) and radiotherapy (RT) have served as anticancer treatments and neoadjuvant therapies for conquering multimodal rectal cancers including colorectal carcinoma (CRC), yet the concomitant radiation-induced colorectal fibrosis (RICF) has caused chronic toxicity and stenosis in the colorectal mucosa of patients. Mesenchymal stem/stromal cells (MSCs) with unique bidirectional immunoregulation and anti-fibrotic effect have been recognized as splendid sources for regenerative purposes including intestinal diseases. Herein, we are aiming to verify the feasibility and variations of MSC-based cytotherapy for the remission of RICF from the pathological features and the potential impact upon the transcriptomic signatures of RICF rats. For the purpose, we utilized our well-established RICF Sprague-Dawley (SD) rats by radiation for five weeks, and conducted consecutive intraperitoneal injection of two distinct MSCs for treatment, including MSCs derived from adult adipose tissue (AD-MSCs) and perinatal umbilical cord (UC-MSCs). On the one hand, the efficacy of AD-MSCs and UC-MSCs was assessed by diverse indicators, including weight change, pathological detections (e.g., H&E staining, Masson staining, EVG staining, IF staining, and IHC staining), and proinflammatory and fibrotic factor expression. On the other hand, we turned to RNA-sequencing (RNA-SEQ) and multifaceted bioinformatics analyses (e.g., GOBP, Venn Map, KEGG, and GSEA) to compare the impact of AD-MSC and UC-MSC treatment upon the gene expression profiling and genetic variations. RICF rats after consecutive AD-MSC and UC-MSC administration revealed comparable remission in histopathogenic features and significant suppression of diverse proinflammatory and fibrotic factors expression. Meanwhile, RICF rats after both MSC treatment revealed decrease and variations in the alterations in diverse gene expression and somatic mutations compared to RICF rats. Collectively, our data indicated the comparable therapeutic effect of AD-MSCs and UC-MSCs upon RICF in SD rats, together with the conservations in gene expression profiling and the diverse variations in genetic mutations. Our findings indicated the multifaceted impact of MSC infusion for the supervision of RICF both at the therapeutic and transcriptomic levels, which would provide novel references for the further evaluation and development of MSC-based regimens in future.

Evaluation of next-generation sequencing for measurable residual disease monitoring in three major fusion transcript subtypes of B-precursor acute lymphoblastic leukaemia.

The use of next-generation sequencing (NGS) for monitoring measurable residual disease (MRD) in acute lymphoblastic leukaemia (ALL) has been gaining traction. This study aimed to investigate the utility of NGS in MRD monitoring for the three major fusion transcript (FT) subtypes of B-precursor ALL (B-ALL). The MRD results for 104 bone marrow samples from 56 patients were analysed through NGS and real time quantitative reverse transcription PCR (RT-qPCR) for the three major FTs: BCR::ABL1, TCF3::PBX1, and ETV6::RUNX1. To validate the NGS approach, NGS-MRD was initially compared with allele-specific oligonucleotide-qPCR-MRD, and the coefficient of determination was good (R2=0.8158). A subsequent comparison of NGS-MRD with FT-MRD yielded a good coefficient of determination (R2=0.7690), but the coefficient varied by subtype. Specifically, the R2 was excellent for TCF3::PBX1 ALL (R2=0.9157), good for ETV6::RUNX1 ALL (R2=0.8606), and subpar for BCR::ABL1 ALL (R2=0.5763). The overall concordance between the two methods was 83.7%, and an excellent concordance rate of 95.8% was achieved for TCF3::PBX1 ALL. Major discordance, which was defined as a >1 log difference between discordant NGS-MRD and FT-MRD, occurred in 6.7% of the samples, with all but one sample being BCR::ABL1 ALL. Among the four non-transplanted patients with BCR::ABL1-MRD (+)/NGS-MRD (-), three did not relapse after long-term follow-up. Our finding indicates that NGS-MRD has a better prognostic impact than RT-qPCR-MRD in ETV6::RUNX1 and BCR::ABL1 ALL, whereas in TCF3::PBX1 ALL, both methods exhibit comparable efficacy.

Flavomycin restores colistin susceptibility in multidrug-resistant Gram-negative bacteria.

Polymyxin is used as a last resort antibiotics for infections caused by multi-drug resistant (MDR) Gram-negative bacteria and is often combined with other antibiotics to improve clinical effectiveness. However, the synergism of colistin and other antibiotics remains obscure. Here, we revealed a notable synergy between colistin and flavomycin, which was traditionally used as an animal growth promoter and has limited activity against Gram-negative bacteria, using checkerboard assay and time-kill curve analyses. The importance of membrane penetration induced by colistin was assessed by examining the intracellular accumulation of flavomycin and its antimicrobial impact on Escherichia coli (E. coli) strains with truncated lipopolysaccharides. Besides, a mutation in the flavomycin binding site was created to confirm its role in the observed synergy. This synergy is manifested as an augmented penetration of the E. coli outer membrane by colistin, leading to increased intracellular accumulation of flavomycin and enhanced cell killing thereafter. The observed synergy was dependent on the antimicrobial activity of flavomycin, as mutation of its binding site abolished the synergy. In vivo studies confirmed the efficacy of colistin combined with flavomycin against MDR E. coli infections. This study is the first to demonstrate the synergistic effect between colistin and flavomycin, shedding light on their respective roles in this synergism. Therefore, we propose flavomycin as an adjuvant to enhance the potency of colistin against MDR Gram-negative bacteria. IMPORTANCE: Colistin is a critical antibiotic in combating multi-drug resistant Gram-negative bacteria, but the emergence of mobilized colistin resistance (mcr) undermines its effectiveness. Previous studies have found that colistin can synergy with various drugs; however, its exact mechanisms with hydrophobic drugs are still unrevealed. Generally, the membrane destruction of colistin is thought to be the essential trigger for its interactions with its partner drugs. Here, we use clustered regularly interspaced palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) for specifically mutating the binding site of one hydrophobic drug (flavomycin) and show that antimicrobial activity of flavomycin is critical for the synergy. Our results first give the evidence that the synergy is set off by colistin's membrane destruction and operated the final antimicrobial function by its partner drugs.

Differences in tourism economic development and its influencing factors among three major city clusters along the middle reaches of the Yangtze River.

An in-depth study of the mechanisms governing the generation, evolution, and regulation of differences in tourism economics holds significant value for the rational utilization of tourism resources and the promotion of synergistic tourism economic development. This study utilizes mathematical statistical analysis and GIS spatial analysis to construct a single indicator measure and a comprehensive indicator measure to analyze tourism-related data in the research area from 2004 to 2019. The main factors influencing the spatial and temporal differences in the tourism economy are analyzed using two methods, namely, multiple linear regression and geodetector. The temporal evolution, overall differences and differences within each city group fluctuate downwards, while the differences between groups fluctuate upwards. Domestic tourism economic differences contribute to over 90% of the overall tourism economic differences. Spatial divergence, the proportion of the tourism economy accounted for by spatial differences is obvious, the comprehensive level of the tourism economy can be divided into five levels. The dominant factors in the formation of the pattern of spatial and temporal differences in the tourism economy are the conditions of tourism resources based on class-A tourist attractions and the level of tourism industry and services based on star hotels and travel agencies. This study addresses the regional imbalance of tourism economic development in city clusters and with the intent of promoting balanced and high-quality development of regional tourism economies.

Gate-Tunable Positive and Negative Photoconductance in Near-Infrared Organic Heterostructures for In-Sensor Computing.

The rapid growth of sensor data in the artificial intelligence often causes significant reductions in processing speed and power efficiency. Addressing this challenge, in-sensor computing is introduced as an advanced sensor architecture that simultaneously senses, memorizes, and processes images at the sensor level. However, this is rarely reported for organic semiconductors that possess inherent flexibility and tunable bandgap. Herein, an organic heterostructure that exhibits a robust photoresponse to near-infrared (NIR) light is introduced, making it ideal for in-sensor computing applications. This heterostructure, consisting of partially overlapping p-type and n-type organic thin films, is compatible with conventional photolithography techniques, allowing for high integration density of up to 520 devices cm-2 with a 5 µm channel length. Importantly, by modulating gate voltage, both positive and negative photoresponses to NIR light (1050 nm) are attained, which establishes a linear correlation between responsivity and gate voltage and consequently enables real-time matrix multiplication within the sensor. As a result, this organic heterostructure facilitates efficient and precise NIR in-sensor computing, including image processing and nondestructive reading and classification, achieving a recognition accuracy of 97.06%. This work serves as a foundation for the development of reconfigurable and multifunctional NIR neuromorphic vision systems.

Analysis of the Immunogenicity of African Swine Fever F317L Protein and Screening of T Cell Epitopes.

The African swine fever virus (ASFV) encodes numerous proteins characterized by complex immune escape mechanisms. At present, the structure and function of these proteins, including the F317L protein, have yet to be fully elucidated. In this study, we examined the immunogenicity of the F317L protein. Mice were subcutaneously immunized with the F317L protein using initial and subsequent booster doses, and, at the 28th day post-treatment, we assessed the humoral and cellular immune responses of mice. The F317L protein stimulated production of specific antibodies and activated humoral immune responses. In addition, F317L stimulated the production of large amounts of IFN-γ by splenic lymphocytes, thereby activating cellular immune responses. Using informatics technology, we predicted and synthesized 29 F317L protein T cell epitopes, which were screened using IFN-γ ELISpot. Among these, the F25 (246SRRSLVNPWT255) peptide was identified as having a stronger stimulatory effect than the full-length protein. Collectively, our findings revealed that the ASFV F317L protein can stimulate both strong humoral and cellular immunity in mice, and that the F25 (246SRRSLVNPWT255) peptide may be a potential active T cell epitope. These findings will provide a reference for further in-depth studies of the F317L protein and screening of antigenic epitopes.

Measurable Residual FLT3 Internal Tandem Duplication Before Allogeneic Transplant for Acute Myeloid Leukemia.

Importance: Persistence of FLT3 internal tandem duplication (ITD) in adults with acute myeloid leukemia (AML) in first complete remission (CR) prior to allogeneic hematopoietic cell transplant (HCT) is associated with increased relapse and death after transplant, but the association between the level of measurable residual disease (MRD) detected and clinical outcome is unknown. Objective: To examine the association between pre-allogeneic HCT MRD level with relapse and death posttransplant in adults with AML in first CR. Design, Setting, and Participants: In this cohort study, DNA sequencing was performed on first CR blood from patients with FLT3-ITD AML transplanted from March 2013 to February 2019. Clinical follow-up was through May 2022. Data were analyzed from October 2022 to December 2023. Exposure: Centralized DNA sequencing for FLT3-ITD in pre-allogeneic HCT first CR blood using a commercially available kit. Main Outcomes and Measures: The primary outcomes were overall survival and cumulative incidence of relapse, with non-relapse-associated mortality as a competing risk post-allogeneic HCT. Kaplan-Meier estimations (log-rank tests), Cox proportional hazards models, and Fine-Gray models were used to estimate the end points. Results: Of 537 included patients with FLT3-ITD AML from the Pre-MEASURE study, 296 (55.1%) were female, and the median (IQR) age was 55.6 (42.9-64.1) years. Using the variant allele fraction (VAF) threshold of 0.01% or greater for MRD positivity, the results closely aligned with those previously reported. With no VAF threshold applied (VAF greater than 0%), 263 FLT3-ITD variants (median [range] VAF, 0.005% [0.0002%-44%]), and 177 patients (33.0%) with positive findings were identified. Multivariable analyses showed that residual FLT3-ITD was the variable most associated with relapse and overall survival, with a dose-dependent correlation. Patients receiving reduced-intensity conditioning without melphalan or nonmyeloablative conditioning had increased risk of relapse and death at any given level of MRD compared with those receiving reduced-intensity conditioning with melphalan or myeloablative conditioning. Conclusions and Relevance: This study provides generalizable and clinically applicable evidence that the detection of residual FLT3-ITD in the blood of adults in first CR from AML prior to allogeneic HCT is associated with an increased risk of relapse and death, particularly for those with a VAF of 0.01% or greater. While transplant conditioning intensification, an intervention not available to all, may help mitigate some of this risk, alternative approaches will be necessary for this high-risk population of patients who are underserved by the current standard of care.

The impact of Sangju Qingjie Decoction on the pulmonary microbiota in the prevention and treatment of chronic obstructive pulmonary disease.

Objective: Exploring the effect of SJQJD on the pulmonary microbiota of chronic obstructive pulmonary disease (COPD) rats through 16S ribosomal RNA (rRNA) sequencing. Methods: A COPD rat model was constructed through smoking and lipopolysaccharide (LPS) stimulation, and the efficacy of SJQJD was evaluated by hematoxylin and eosin (H&E) staining and Enzyme-Linked Immunosorbnent Assay (ELISA). The alveolar lavage fluid of rats was subjected to 16S rRNA sequencing. The diversity of lung microbiota composition and community structure was analyzed and differential microbiota were screened. Additionally, machine learning algorithms were used for screening biomarkers of each group of the microbiota. Results: SJQJD could improve lung structure and inflammatory response in COPD rats. 16s rRNA sequencing analysis showed that SJQJD could significantly improve the abundance and diversity of bacterial communities in COPD rats. Through differential analysis and machine learning methods, potential microbial biomarkers were identified as Mycoplasmataceae, Bacillaceae, and Lachnospiraceae. Conclusion: SJQJD could improve tissue morphology and local inflammatory response in COPD rats, and its effect may be related to improve pulmonary microbiota.