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Phormia regina (Meigen, 1826; Diptera: Calliphoridae) is a Holarctic species that rapidly colonizes carcasses and has been used as an indicator for determining the minimum postmortem interval. However, studies using morphological methods to estimate the intrapuparial age of P. regina are lacking. In this study, morphological changes within the puparium were observed under a stereomicroscope at 7 constant temperatures ranging from 16 °C to 34 °C. The intrapuparial period was categorized into 12 substages. Morphological indicators, including compound eyes, mouthparts, antennae, thorax, legs, wings, and abdomen, were recorded in detail. The observed morphological changes were divided into 6-10 substages, and the duration of each substage was also recorded in detail. The results of this study provide primary data for using the intrapuparial morphology of P. regina when pupae are collected at a crime scene and estimating the minimum postmortem interval., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Accurate postmortem interval estimation is vital in the investigation of homicides, suicides, and accidental deaths. It is key in narrowing suspect lists, improving crime-solving efficiency, and offering solace to bereaved families. The intra-puparial period, comprising about half of a fly's developmental cycle, presents challenges for morphological age estimation. External changes are limited to color shifts and the appearance of respiratory horns on the puparium only within several hours after pupariation, while detailed internal development analysis often requires invasive methods like removing the puparium, which can be damaging. Additionally, these techniques usually depend on a forensic entomologist's expertise, which lead to subjective biases. This study employed attenuated total reflection-fourier transform infrared spectroscopy, a rapid, non-destructive method for analyzing proteins, chitosan, and chitin in puparia. Data showed a consistent reduction in the concentration of the amide I band within the puparium during the intra-puparial development at five constant temperatures (19 °C, 22 °C, 25 °C, 28 °C and 31 °C). This trend in the spectral data effectively distinguishes pupae at various stages of intra-puparial development, facilitating precise age estimation, which is critical for the estimation of the minimum postmortem interval (PMI min ). Finally, this work combined the total reflection-fourier transform infrared spectroscopy with chemometric analysis and successfully developed a partial least squares discriminant analysis model and a random forest model, with accuracies of 88 % and 81 %, respectively. These models enable the non-invasive age estimation of P. regina in its intra-puparial period, a stage traditionally difficult to assess morphologically, thus laying the groundwork for PMI min estimation using fly pupae., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Intestinal fibrosis is the primary cause of disability in patients with Crohn's disease (CD), yet effective therapeutic strategies are currently lacking. Here, we report a multiomics analysis of gut microbiota and fecal/blood metabolites of 278 CD patients and 28 healthy controls, identifying characteristic alterations in gut microbiota (e.g., Lachnospiraceae, Ruminococcaceae, Muribaculaceae, Saccharimonadales) and metabolites (e.g., L-aspartic acid, glutamine, ethylmethylacetic acid) in moderate-severe intestinal fibrosis. By integrating multiomics data with magnetic resonance enterography features, putative links between microbial metabolites and intestinal fibrosis-associated morphological alterations were established. These potential associations were mediated by specific combinations of amino acids (e.g., L-aspartic acid), primary bile acids, and glutamine. Finally, we provided causal evidence that L-aspartic acid aggravated intestinal fibrosis both in vitro and in vivo. Overall, we offer a biologically plausible explanation for the hypothesis that gut microbiota and its metabolites promote intestinal fibrosis in CD while also identifying potential targets for therapeutic trials., (© 2024. The Author(s).)

In this paper, a set of novel ternary deep eutectic solvents (T-DESs) is synthesized and applied in the esterification of 2-methylpropenoic acid with alcohols. T-DESs have multiple functions, serving as a catalyst, polymerization inhibitor, and solvent, and demonstrate excellent catalytic esterification reaction activity (up to 96% yield). The optimal T-DESs 1 can be recycled 14 times without any decrease in its catalytic activity, thus solving the problems of methacrylate product separation with a polymerization inhibitor, catalyst recovery, and organic solvent pollution.

Rationale : the proto-oncogene KRAS is frequently mutated in colorectal cancer (CRC), leading to inherent resistance against monoclonal antibodies targeting the epidermal growth factor receptor (EGFR), such as cetuximab. Therefore, addressing the primary resistance and expanding the indications for target therapy have become critical challenges. Methods : the screening of a natural product library against KRAS mutant CRC cells was conducted, leading to the discovery of a small molecule compound that sensitive to the KRAS G13D mutation site. The anti-tumor activity of this small molecule compound in combination with cetuximab was evaluated using the KRAS G13D mutant CRC models both in vivo and in vitro . This evaluation includes an examination of its effects on cell proliferation, viability, apoptosis, cell cycle progression, and tumor growth. Furthermore, RNA sequencing, western blot analysis, immunofluorescence, real-time quantitative PCR, and pull-down assays were employed to explore the molecular mechanisms underlying the synergistic anti-tumor effect of this small molecule compound in combination with cetuximab. Results : our study screened 882 compounds in KRAS mutant CRC cells and identified honokiol, a small molecule compound that exhibits specific sensitivity to KRAS G13D mutant CRC cells. Furthermore, we revealed that the synergistic augmentation of cetuximab's sensitivity in vivo and in vitro models of KRAS G13D mutant CRC in combination with honokiol. Mechanistically, honokiol suppresses SNX3-retromer mediated trafficking, thereby impeding lysosomal proteolytic capacity and inhibiting autophagy and macropinocytosis fluxes. Moreover, honokiol inhibits the conversion of RAS GDP to RAS GTP, heightening the susceptibility of KRAS G13D CRC mutant cells to cetuximab. Conclusions : honokiol enhances the sensitivity of cetuximab by destroying SNX3 retromer in KRAS G13D mutant CRC preclinical model. These findings present a promising strategy for expanding the indications of target therapy in KRAS mutant colorectal cancer patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Plasma proteins are promising biomarkers and potential drug targets for stroke. This study aimed to explore whether there is a causal relationship between plasma proteins and subtypes of stroke using a Mendelian randomization (MR) approach. A two-sample bidirectional Mendelian randomization approach was employed to investigate the causal link between plasma proteins and stroke. Data on plasma proteins were obtained from three studies, including INTERVAL, and pooled stroke information was sourced from the MEGASTROKE consortium and the UK Biobank dataset, covering four subtypes of stroke. MR analyses were primarily conducted using inverse variance weighting, and sensitivity analyses were also performed. Finally, potential reverse causality was assessed using bidirectional MR. We identified two proteins causally associated with stroke: one as a potential therapeutic target and another as a protective factor. CXCL8 was found to be positively associated with the risk of developing large-artery atherosclerotic (LAA) stroke (OR, 1.005; 95% CI 1.001 to 1.010; p = 0.022), whereas TNFRSF11b was negatively correlated with the risk of developing LAA stroke (OR, 0.937; 95% CI 0.892 to 0.984; p = 0.010), independently of other stroke subtypes. Reverse bivariate analysis did not indicate that ischemic stroke was causally associated with CXCL8 and TNFRSF11b. There is a causal relationship between CXCL8 and TNFRSF11b with LAA stroke, independent of other subtypes. This study offers a new perspective on the genetics of stroke., (© 2024. The Author(s).)

Necrophagous beetles are sometimes used to estimate the minimum postmortem interval (PMI min ) in the decay and remains stages of a corpse. Among these, the Dermestidae is one of the most common groups used and therefore has important research and application value. In this study, the developmental events of Dermestes maculatus de Geer, 1774, were recorded at six constant temperatures, and isomorphen diagrams were established. The thermobiological parameters were estimated using linear and non-linear models, and morphological indicators such as larval body length were measured. The results showed that the developmental duration of the whole immature stage decreased from 66.13 ± 8.58 days at 19 °C to 21.9 ± 2.01 days at 34 °C. The survival rate of the immature stages, especially the egg stage, varies greatly with temperature, with the lowest survival observed at 34 °C and the highest at 22 °C. The lower developmental threshold, the intrinsic optimum temperature, and the upper lethal developmental threshold obtained by the curvilinear Optim SSI models were 15.28 °C, 28.36 °C, and 34.03 °C, respectively. The body length, head capsule width, and pronotum width showed obvious growth patterns with larval developmental duration, which were characterized by equations and isomegalen diagrams. This study provides important basic data for the application of D. maculatus to estimate the PMI min in forensic entomology in the Yangtze River Delta region of China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Chartered Society of Forensic Sciences. Published by Elsevier B.V. All rights reserved.)

Objectives: Differentiating intestinal tuberculosis (ITB) from Crohn's disease (CD) remains a diagnostic dilemma. Misdiagnosis carries potential grave implications. We aim to establish a multidisciplinary-based model using machine learning approach for distinguishing ITB from CD., Methods: Eighty-two patients including 25 patients with ITB and 57 patients with CD were retrospectively recruited (54 in training cohort and 28 in testing cohort). The region of interest (ROI) for the lesion was delineated on magnetic resonance enterography (MRE) and colonoscopy images. Radiomic features were extracted by least absolute shrinkage and selection operator regression. Pathological feature was extracted automatically by deep-learning method. Clinical features were filtered by logistic regression analysis. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Delong's test was applied to compare the efficiency between the multidisciplinary-based model and the other four single-disciplinary-based models., Results: The radiomics model based on MRE features yielded an AUC of 0.87 (95% confidence interval [CI] 0.68-0.96) on the test data set, which was similar to the clinical model (AUC, 0.90 [95% CI 0.71-0.98]) and higher than the colonoscopy radiomics model (AUC, 0.68 [95% CI 0.48-0.84]) and pathology deep-learning model (AUC, 0.70 [95% CI 0.49-0.85]). Multidisciplinary model, integrating 3 clinical, 21 MRE radiomic, 5 colonoscopy radiomic, and 4 pathology deep-learning features, could significantly improve the diagnostic performance (AUC of 0.94, 95% CI 0.78-1.00) on the bases of single-disciplinary-based models. DCA confirmed the clinical utility., Conclusions: Multidisciplinary-based model integrating clinical, MRE, colonoscopy, and pathology features was useful in distinguishing ITB from CD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To review the literature on the relationship of milk fat globule EGF and factor V/VIII domain containing (MFGE8) in periodontal osteoimmunology and the clinical significance of MFGE8 in periodontal disease., Methods: Two reviewers carried out a computer-based literature search using PubMed, Scopus, and Web of Science to identify papers published up to November 2023. The keywords used in the investigation were "MFGE8" and various words related to periodontal disease (periodontal, periodontitis, gingival, gingivitis, gingiva, and periodontium)., Results: MFGE8 plays a critical role in the etiology of periodontal disease via regulating pro-inflammatory cytokines and bone cells. In addition, MFGE8 may be applied as a diagnostic biomarker and a therapeutic target in periodontal disease., Clinical Significance: MFGE8-mediated periodontal osteoimmunology fills the vacant part of the pathogenesis in periodontal disease. This review provides a comprehensive perspective on the potential of MFGE8 in periodontal disease therapy., Competing Interests: The authors declared no conflict of interest. This work was supported by the Natural Science Foundation of Hubei Province of China under Grant (number 2022CFB293 and 2023AFB653); the National Natural Science Foundation of China under Grant (number 81300883); Wuhan Innovative Talent Development Funds 2014; and Scientific Research Foundation for Returned Scholars, Tongji Hospital 2016., (Copyright©American Journal of Dentistry.)

Hematoma expansion (HE) is a high risky symptom with high rate of occurrence for patients who have undergone spontaneous intracerebral hemorrhage (ICH) after a major accident or illness. Correct prediction of the occurrence of HE in advance is critical to help the doctors to determine the next step medical treatment. Most existing studies focus only on the occurrence of HE within 6 h after the occurrence of ICH, while in reality a considerable number of patients have HE after the first 6 h but within 24 h. In this study, based on the medical doctors recommendation, we focus on prediction of the occurrence of HE within 24 h, as well as the occurrence of HE every 6 h within 24 h. Based on the demographics and computer tomography (CT) image extraction information, we used the XGBoost method to predict the occurrence of HE within 24 h. In this study, to solve the issue of highly imbalanced data set, which is a frequent case in medical data analysis, we used the SMOTE algorithm for data augmentation. To evaluate our method, we used a data set consisting of 582 patients records, and compared the results of proposed method as well as few machine learning methods. Our experiments show that XGBoost achieved the best prediction performance on the balanced dataset processed by the SMOTE algorithm with an accuracy of 0.82 and F1-score of 0.82. Moreover, our proposed method predicts the occurrence of HE within 6, 12, 18 and 24 h at the accuracy of 0.89, 0.82, 0.87 and 0.94, indicating that the HE occurrence within 24 h can be predicted accurately by the proposed method., (© 2024. The Author(s).)

Purpose: Accurately and early detection of intestinal fibrosis in Crohn's disease (CD) is crucial for clinical management yet remains an unmet need. Fibroblast activation protein inhibitor (FAPI) PET/CT has emerged as a promising tool to assess fibrosis. We aimed to investigate the diagnostic capability of [ 18 F]F-FAPI PET/CT in detecting intestinal fibrosis and compared it with[ 18 F]F-FDG PET/CT and magnetization transfer MR imaging (MTI)., Methods: Twenty-two rats underwent TNBS treatment to simulate fibrosis development, followed by three quantitative imaging sessions within one week. Mean and maximum standardized uptake values (SUV mean and SUV max ) were calculated on[ 18 F]F-FAPI and [ 18 F]F-FDG PET/CT, along with normalized magnetization transfer ratio on MTI. Intestinal fibrosis was assessed pathologically, with MTI serving as imaging standard for fibrosis. The diagnostic efficacy of imaging parameters in fibrosis was compared using pathological and imaging standards. Ten patients with 34 bowel strictures were prospectively recruited to validate their diagnostic performance, using the identical imaging protocol., Results: In CD patients, the accuracy of FAPI uptake (both AUCs = 0.87, both P ≤ 0.01) in distinguishing non-to-mild from moderate-to-severe fibrosis was higher than FDG uptake (both AUCs = 0.82, P ≤ 0.01) and comparable to MTI (AUCs = 0.90, P ≤ 0.001). In rats, FAPI uptake responded earlier to fibrosis development than FDG and MTI; consistently, during early phase, FAPI uptake showed a stronger correlation (SUV mean : R = 0.69) with pathological fibrosis than FDG (SUV mean : R = 0.17) and MTI (R = 0.52)., Conclusion: The diagnostic efficacy of [ 18 F]F-FAPI PET/CT in detecting CD fibrosis is superior to [ 18 F]F-FDG PET/CT and comparable to MTI, exhibiting great potential for early detection of intestinal fibrosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

High expression of programmed cell death protein 1 (PD-1), a typical immune checkpoint, results in dysfunction of T cells in tumor microenvironment. Antibodies and inhibitors against PD-1 or its ligand (PD-L1) have been widely used in various malignant tumors. However, the mechanisms by which PD-1 is regulated are not fully understood. Here, we report a mechanism of PD-1 degradation triggered by d-mannose and the universality of this mechanism in anti-tumor immunity. We show that d-mannose inactivates GSK3β via promoting phosphorylation of GSK3β at Ser9, thereby leading to TFE3 translocation to nucleus and subsequent PD-1 proteolysis induced by enhanced lysosome biogenesis. Notably, combination of d-mannose and PD-1 blockade exhibits remarkable tumor growth suppression attributed to elevated cytotoxicity activity of T cells in vivo. Furthermore, d-mannose treatment dramatically improves the therapeutic efficacy of MEK inhibitor (MEKi) trametinib in vivo. Our findings unveil a universally unrecognized anti-tumor mechanism of d-mannose by destabilizing PD-1 and provide strategies to enhance the efficacy of both immune checkpoint blockade (ICB) and MEKi -based therapies., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Radix Astragali (Huangqi in Chinese, HQ) is a commonly used Chinese herbal medicine for thousands of years. In this study, A classic prescription Huangqi Jianzhong tang (HQJZ) was selected to evaluate the important effect of HQ on rats with chronic atrophic gastritis (CAG) from the perspective of intestinal flora in cecal contents samples. Traditional pharmacological indicators, including weight change, pathological examination and biochemical indicators showed that HQ exerted favorable contribution to HQJZ against CAG, where the efficiencies of HQ and HQJZ were better than HY (HQJZ prepared without HQ). An accurate strategy was adopted to screen out the differential metabolites in the metabolomis analysis of intestinal flora in cecal contents samples based on the optimal screening factors, including VIP (importance of variables in projection), FC (fold change), AUROC (area under the receiver operating characteristic curve) and -ln(p-value), which were evaluated based on their interpreting, grouping, and predicting abilities of the performed orthogonal partial least-squares-discriminate analysis (OPLS-DA) models. Ten altered differential metabolites were obtained and associated with the intestinal flora, which HQ exerted the important metabolic contributions to HQJZ. The efficacy on the diversity of intestinal flora and their correlations with the altered metabolites further showed the important role of HQ in HQJZ composition. This work provided valuable approach for looking for potential biomarkers associated with metabolomics research with more accuracy, and provided new insights into the mechanisms to explain the efficacy of HQ contributing to HQJZ formula., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Lung cancer is a leading cause of mortality worldwide, especially among Asian patients with non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) mutations. Initially, first-generation EGFR tyrosine kinase inhibitors (TKIs) are commonly administered as the primary treatment option; however, encountering resistance to these medications poses a significant obstacle. Hence, it has become crucial to address initial resistance and ensure continued effectiveness. Recent research has focused on the role of long noncoding RNAs (lncRNAs) in tumor drug resistance, especially lncRNA H19. β-elemene, derived from Curcuma aromatic Salisb., has shown strong anti-tumor effects. However, the relationship between β-elemene, lncRNA H19, and gefitinib resistance in NSCLC is unclear. This study aims to investigate whether β-elemene can enhance the sensitivity of gefitinib-resistant NSCLC cells to gefitinib and to elucidate its mechanism of action. The impact of gefitinib and β-elemene on cell viability was evaluated using the cell counting kit-8 (CCK8) assay. Furthermore, western blotting and qRT-PCR analysis were employed to determine the expression levels of autophagy-related proteins and genes, respectively. The influence on cellular proliferation was gauged through a colony-formation assay, and apoptosis induction was quantified via flow cytometry. Additionally, the tumorigenic potential in vivo was assessed using a xenograft model in nude mice. The expression levels of LC3B, EGFR, and Rab7 proteins were examined through immunofluorescence. Our findings elucidate that the resistance to gefitinib is intricately linked with the dysregulation of autophagy and the overexpression of lncRNA H19. The synergistic administration of β-elemene and gefitinib markedly attenuated the proliferative capacity of resistant cells, expedited apoptotic processes, and inhibited the in vivo proliferation of lung cancer. Notably, β-elemene profoundly diminished the expression of lncRNA H19 and curtailed autophagic activity in resistant cells, thereby bolstering their responsiveness to gefitinib. Moreover, β-elemene disrupted the Rab7-facilitated degradation pathway of EGFR, facilitating its repositioning to the plasma membrane. β-elemene emerges as a promising auxiliary therapeutic for circumventing gefitinib resistance in NSCLC, potentially through the regulation of lncRNA H19-mediated autophagy. The participation of Rab7 in this dynamic unveils novel insights into the resistance mechanisms operative in lung cancer, paving the way for future therapeutic innovations.

Phormia regina (Meigen, 1826) (Diptera: Calliphoridae) can colonize carcasses quickly, and its immature stages are reliable entomological evidence for the estimation of the minimum postmortem interval (PMI min ). There are discrepancies in the developmental data from previous studies on P. regina, and the related PMI min indicators need to be refined. We investigated the accuracy of forensic entomological evidence using development durations, growth accumulated degree hours, and larval body length variations of P. regina at seven constant temperatures ranging from 16 to 34 °C. We also established development models such as the isomorphen diagram, thermal summation model, isomegalen diagram, and body length simulation equation to assist with PMI min estimation. The developmental duration of P. regina from egg to adult at 16, 19, 22, 25, 28, 31, and 34 °C was 840.8 ± 42.8 h, 580.1 ± 10.1 h, 390.4 ± 8.7 h, 316.8 ± 9.4 h, 291.4 ± 21.2 h, 238.4 ± 2.8 h, and 222.5 ± 5.2 h, respectively. The lower threshold temperature T L was 9.97 ± 0.50 °C, while the thermal constant K was 5052.7 ± 229 degree days. The lower developmental thresholds, intrinsic optimum temperature, and upper lethal developmental threshold obtained by the Optim SSI models were 13.15, 21.20, and 36.86 °C, respectively. This study aims to provide developmental models for P. regina aimed at common case-site temperatures in the northern provinces of China, which can be used for accurate PMI min estimation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: A biological system's internal morphological structure or function can be changed as a result of the mechanical effect of focused ultrasound. Pulsed low-intensity focused ultrasound (LIFU) has mechanical effects that might induce follicle development with less damage to ovarian tissue. The potential development of LIFU as a non-invasive method for the treatment of female infertility is being considered, and this study sought to explore and confirm that LIFU can activate ovarian follicles. Results: We found a 50% increase in ovarian weight and in the number of mature follicles on the ultrasound-stimulated side with pulsed LIFU and intraperitoneal injection of 10 IU PMSG in 10-day-old rats. After ultrasound stimulation, the PCOS-like rats had a decrease in androgen levels, restoration of regular estrous cycle and increase in the number of mature follicles and corpora lutea, and the ratio of M1 and M2 type macrophages was altered in antral follicles of PCOS-like rats, consequently promoting further development and maturation of antral follicles. Conclusion: LIFU treatment could trigger actin changes in ovarian cells, which might disrupt the Hippo signal pathway to promote follicle formation, and the mechanical impact on the ovaries of PCOS-like rats improved antral follicle development., (© 2024 The Authors.)

Purpose: To investigate the clinical characteristics, etiology, and risk factors of bacterial bloodstream infection (BSI) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. This study also aimed to provide a clinical basis for early identification of high-risk patients and optimization of empirical antimicrobial treatment., Patients and Methods: This is a retrospective study of clinical data during agranulocytosis from 331 patients with hematological malignancies who underwent allo-HSCT at our institute between January 2016 and December 2022. The incidence, distribution and drug resistance patterns, and the risk factors of BSI were analyzed., Results: Among the 331 HSCT patients, 250 had febrile neutropenia and 45 cases were found to have BSI. The incidence of BSI in patients with agranulocytosis fever was 18% (45/250). A total of 48 pathogens were isolated during BSI episodes, gram-negative bacteria (GNB) accounted for 70.8% (34/48), gram-positive bacteria (GPB) for 29.2% (14/48). Multivariate analysis revealed that ≥grade 2 acute graft-versus-host disease (aGVHD) and previous BSI within 6 months before HSCT were independently associated with an increased occurrence of BSI. Coagulase-negative staphylococci (CoNS) and Escherichia coli were the most commonly isolated GPB and GNB, respectively. A total of 32 GNB were tested for drug susceptibility, the detection rate of carbapenem-resistant Enterobacteriaceae (CRE) was 12.5% (4/32), and extended-spectrum β-lactamase (ESBL) accounted for 56.3% (18/32)., Conclusion: BSIs are still a common and severe complication after allo-HSCT. In our center, BSIs in allo-HSCT patients are dominated by gram-negative bacteria and the resistance rate to carbapenem drugs is high. Risk factors for BSI during agranulocytosis were previous BSI within 6 months before HSCT and ≥grade 2 aGVHD., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Zhang et al.)

Scene Graph Generation (SGG) aims to detect visual relationships in an image. However, due to long-tailed bias, SGG is far from practical. Most methods depend heavily on the assistance of statistics co-occurrence to generate a balanced dataset, so they are dataset-specific and easily affected by noises. The fundamental cause is that SGG is simplified as a classification task instead of a reasoning task, thus the ability capturing the fine-grained details is limited and the difficulty in handling ambiguity is increased. By imitating the way of dual process in cognitive psychology, a Visual-Textual Semantics Consistency Network (VTSCN) is proposed to model the SGG task as a reasoning process, and relieve the long-tailed bias significantly. In VTSCN, as the rapid autonomous process (Type1 process), we design a Hybrid Union Representation (HUR) module, which is divided into two steps for spatial awareness and working memories modeling. In addition, as the higher order reasoning process (Type2 process), a Global Textual Semantics Modeling (GTS) module is designed to individually model the textual contexts with the word embeddings of pairwise objects. As the final associative process of cognition, a Heterogeneous Semantics Consistency (HSC) module is designed to balance the type1 process and the type2 process. Lastly, our VTSCN raises a new way for SGG model design by fully considering human cognitive process. Experiments on Visual Genome, GQA and PSG datasets show our method is superior to state-of-the-art methods, and ablation studies validate the effectiveness of our VTSCN. The source codes are released on GitHub: https://github.com/Nora-Zhang98/VTSCN.

The long-range transport of dust aerosols plays a crucial role in biogeochemical cycling, and dust deposition is an important source of nutrients for marine phytoplankton growth. To study the impact of COVID-19 emission reduction on dust aerosols and marine chlorophyll-a (Chl-a) concentration, we selected two similar dust processes from the COVID-19 period (10-15 March 2020) and the non-COVID-19 period (15-20 March 2019) using the Euclidean distance calculation method in combination with the HYSPLIT model and multiple satellite data. During the non-COVID-19 period, the proportion of dust was 6.68 %, approximately half that of the COVID-19 period. Meanwhile, the proportion of polluted dust during the non-COVID-19 period was 4.95 %, which was more than tenfold compared to the COVID-19 period. Furthermore, noticeable discrepancies in Chl-a concentration were observed between the two periods. In the non-COVID-19 period, the maximum daily deposition of dust aerosols can reach 16.23 mg/m 2 , resulting in a 39-85 % increase in Chl-a concentration. However, during COVID-19 period, the maximum daily dust deposition can reach 33.33 mg/m 2 , while the increase in Chl-a concentration was <30 %. This conclusion suggests that reductions in anthropogenic emissions during the COVID-19 period have influenced the nutrient content of dust aerosols, resulting in a lesser impact on Chl-a concentrations in the ocean., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Crystal (Cry) toxins, produced by Bacillus thuringiensis , are widely used as effective biological pesticides in agricultural production. However, insects always quickly evolve adaptations against Cry toxins within a few generations. In this study, we focused on the Cry1Ac protoxin activated by protease. Our results identified PxTrypsin-9 as a trypsin gene that plays a key role in Cry1Ac virulence in Plutella xylostella larvae. In addition, P. xylostella miR-2b-3p, a member of the micoRNA-2 (miR-2) family, was significantly upregulated by Cry1Ac protoxin and targeted to PxTrypsin-9 downregulated its expression. The mRNA level of PxTrypsin-9, regulated by miR-2b-3p, revealed an increased tolerance of P. xylostella larvae to Cry1Ac at the post-transcriptional level. Considering that miR-2b and trypsin genes are widely distributed in various pest species, our study provides the basis for further investigation of the roles of miRNAs in the regulation of the resistance to Cry1Ac and other insecticides.

Purpose: To develop a CT-based radiomics model combining with VAT and bowel features to improve the predictive efficacy of IFX therapy on the basis of bowel model., Methods: This retrospective study included 231 CD patients (training cohort, n = 112; internal validation cohort, n = 48; external validation cohort, n = 71) from two tertiary centers. Machine-learning VAT model and bowel model were developed separately to identify CD patients with primary nonresponse to IFX. A comprehensive model incorporating VAT and bowel radiomics features was further established to verify whether CT features extracted from VAT would improve the predictive efficacy of bowel model. Area under the curve (AUC) and decision curve analysis were used to compare the prediction performance. Clinical utility was assessed by integrated differentiation improvement (IDI)., Results: VAT model and bowel model exhibited comparable performance for identifying patients with primary nonresponse in both internal (AUC: VAT model vs bowel model, 0.737 (95% CI, 0.590-0.854) vs. 0.832 (95% CI, 0.750-0.896)) and external validation cohort [AUC: VAT model vs. bowel model, 0.714 (95% CI, 0.595-0.815) vs. 0.799 (95% CI, 0.687-0.885)), exhibiting a relatively good net benefit. The comprehensive model incorporating VAT into bowel model yielded a satisfactory predictive efficacy in both internal (AUC, 0.840 (95% CI, 0.706-0.930)) and external validation cohort (AUC, 0.833 (95% CI, 0.726-0.911)), significantly better than bowel alone (IDI = 4.2% and 3.7% in internal and external validation cohorts, both p < 0.05)., Conclusion: VAT has an effect on IFX treatment response. It improves the performance for identification of CD patients at high risk of primary nonresponse to IFX therapy with selected features from RM., Critical Relevance Statement: Our radiomics model (RM) for VAT-bowel analysis captured the pathophysiological changes occurring in VAT and whole bowel lesion, which could help to identify CD patients who would not response to infliximab at the beginning of therapy., Key Points: • Radiomics signatures with VAT and bowel alone or in combination predicting infliximab efficacy. • VAT features contribute to the prediction of IFX treatment efficacy. • Comprehensive model improved the performance compared with the bowel model alone., (© 2024. The Author(s).)

Macroautophagy/autophagy is a conserved process in eukaryotic cells to degrade and recycle damaged intracellular components. Higher level of autophagy in the brain has been observed, and autophagy dysfunction has an impact on neuronal health, but the molecular mechanism is unclear. In this study, we showed that overexpression of Toll-1 and Toll-7 receptors, as well as active Spätzle proteins in Drosophil a S2 cells enhanced autophagy, and Toll-1/Toll-7 activated autophagy was dependent on Tube-Pelle-PP2A. Interestingly, Toll-1 but not Toll-7 mediated autophagy was dMyd88 dependent. Importantly, we observed that loss of functions in Toll-1 and Toll-7 receptors and PP2A activity in flies decreased autophagy level, resulting in the loss of dopamine (DA) neurons and reduced fly motion. Our results indicated that proper activation of Toll-1 and Toll-7 pathways and PP2A activity in the brain are necessary to sustain autophagy level for DA neuron survival., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Herein, the first lead tellurium borate, PbTeB 4 O 9 , with an unprecedented fundamental building block [B 4 O 10 ] was successfully synthesized. The near-parallel alignment of [B 4 O 10 ] groups and [TeO 3 ] polyhedra resulted in a high birefringence (0.099@1064 nm). The structure-property relationship was discussed by using the first-principles calculations.

Background: D-mannose, an epimer of glucose, which is abundant in some fruits, such as cranberry, has been previously reported to inhibit urinary tract infection. In recent years, the potential function of D-mannose has been broadened into the regulation of other inflammation diseases and cancer. It was reported that D-mannose can increase reactive oxygen species (ROS) production, while IDH2 is important for the generation of NADPH, the crucial reducing factor. These findings prompted us to determine whether D-mannose can regulate IDH2 and IDH2-mediated NADPH production in tumor., Methods: The breast cancer cell line MDA-MB-231 was cultured and treated with 100mM D-mannose. IDH2 expression was detected by Western Blot and qRT-PCR. RNA-seq was conducted to identify the differentially expressed genes. BioGRID database was used to find the IDH2 interactors. Tumor cells were collected to measure the NADPH production using the NADP+/NADPH detection Kit. Colony formation assay and CCK-8 assay were conducted to evaluate the proliferation of cells., Results: D-mannose can promote IDH2 protein degradation through ubiquitination-proteasome pathway. Mechanistically, D-mannose treatment upregulated the expression of an E3 ligase - RNF185, which can interact with IDH2 and promotes its proteasomal degradation. Consequently, IDH2-mediated NADPH production was inhibited by D-mannose, the proliferation of breast cancer cells was retarded, and the sensitivity to pro-oxidant of breast cancer cells was elevated., Conclusions: Our study demonstrated that D-mannose can degrade IDH2 and inhibit the production of NADPH to suppress the proliferation of breast cancer cells and render the breast cancer cells more sensitive to pro-oxidant treatment. Furthermore, we illustrated the E3 ligase RNF185 plays an important role in D-mannose-mediated proteasomal degradation of IDH2., (© 2024. The Author(s).)

The genera Omosita and Nitidula from the family Nitidulidae, are often reported to be associated with rotten animal carcasses. However, morphological descriptions of their larval stages are limited and are usually only from the third instar larvae, which does not provide enough systematic data. In this study, the overall structure of three instar larvae from the four Nitidulidae species was compared using optical microscopy, and the resolution was not satisfactory. To compensate, a large number of structures and organs were observed by scanning electron microscopy (SEM). Results showed that the number and distribution of chaetotaxy in different parts, including the macrosetae, setae, and microtrichia, have important identification values between the genera, species, and even instars. We also discuss the possible role of microtrichia in the biology of Nitidulidae larvae. Additionally, we described the number and types of sensilla in three sensory organs, and the morphologic parameters of the head capsule and urogomphi as determined by SEM images, are provided. An identification key with application value for storage products and forensic entomology was also compiled., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Importance: Our study revealed the spatial interaction between humanized ACE2 and pseudovirus expressing Spike, emphasizing the role of type 2 innate lymphoid cells during the initial phase of viral infection. These findings provide a foundation for the development of mucosal vaccines and other treatment approaches for both pre- and post-infection management of coronavirus disease 2019., Competing Interests: The authors declare no conflict of interest.

Selenocompounds protect against damage to healthy cells and induce the death of tumor cells by apoptosis; for this reason, they are attractive compounds for cancer research. In the present study, two series of novel phenoxy-((phenylethynyl) selanyl) propan-2-ol derivatives were synthesized, and their anti-proliferation activities were evaluated. Of the 23 compounds synthesized, most showed potent anti-proliferative activity against human cancer cell lines. Specifically, compounds 3h, 3g, and 3h-2, which had a 2- or 4-position halogen substituent on 1-((phenylethynyl)selanyl)-3-phenoxypropan-2-ol, exhibited the best anti-proliferative activity against tumor cells. Flow cytometry demonstrated that 3h, 3g, and 3h-2 induced G2/M phase arrest and apoptosis in A549 cells. Cellular studies demonstrated that the induction of apoptosis by 3h correlated with changes in the expression of cell cycle-related proteins and apoptosis-related proteins. Xenograft tumor experiments in nude mice revealed that compound 3h has antitumor effects in vivo and no evident toxic effects in nude mice. In addition, compound 3h alleviated cisplatin-induced liver and kidney damage. These findings uncover the applicability of compound 3h as a novel lead compound for cancer treatment., (© 2023. The Author(s).)

Upregulation of FGL1 helps tumors escape from immune surveillance, and therapeutic antibodies targeting FGL1 have potential as another immune checkpoint inhibitor. However, the underlying mechanism of high FGL1 protein level in cancers is not well defined. Here, we report that FBXO38 interacts with and ubiquitylates FGL1 to negatively regulate its stability and to mediate cancer immune response. Depletion of FBXO38 markedly augments FGL1 abundance, not only suppressing CD8 + T cell infiltration and enhancing immune evasion of tumor but also increasing inflammation in mice. Importantly, we observe a negative correlation of FBXO38 with FGL1 and IL-6 in non-small cell lung cancer specimens. FGL1 and IL-6 levels positively correlate with TNM (tumor, lymph node, metastasis) stages, while FBXO38 and the infiltrating CD8 + T cells negatively correlate with TNM stages. Our study identifies a mechanism regulating FGL1 stability and a target to enhance the immunotherapy and suggests that the combination of anti-FGL1 and anti-IL-6 is a potential therapeutic strategy for cancer immunotherapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In the past few years, immunotherapies of hepatocellular carcinoma (HCC) targeting programmed cell death protein 1 (PD-1) and its ligand programmed cell death ligand 1 (PD-L1), have achieved durable clinical benefits. However, only a fraction of HCC patients showed objective clinical response to PD-1/PD-L1 blockade alone. Despite the impact on post-translational modifications of PD-L1 being substantial, its significance in resistance to HCC immunotherapy remains poorly defined., Methods: Cyclin-dependent kinase 5 (CDK5) expression was knocked down in HCC cells, CDK5 and PD-L1 protein levels were examined by Western blot. Coimmunoprecipitation was conducted to evaluate the interaction between proteins. Preclinical HCC mice model was constructed to evaluate the effect of CDK5 inhibitor alone or in combination with PD-1 antibody. Clinical HCC samples were used to elucidate the clinical relevance of CDK5, PD-L1, and PD-L1 T290 phosphorylation in HCC., Results: We find that CDK5 deficiency upregulates PD-L1 protein expression in HCC cells and decipher a novel molecular mechanism under which PD-L1 is downregulated by CDK5, that is, CDK5 mediated PD-L1 phosphorylation at T290 promotes its binding with chaperon protein heat-shock cognate protein 70 (HSC70) and degradation through chaperon-mediated autophagy. Notably, treatment of CDK5 inhibitor, PNU112455A, effectively upregulates the tumorous PD-L1 level, promotes the response to anti-PD-1 immunotherapy,and prolongs the survival time of mice bearing HCC tumors. What is more, the T290 phosphorylation status of PD-L1 correlates with the prognosis of HCC., Conclusions: Targeting CDK5 can synergize with PD-1 blockade to suppress HCC growth, which may have clinical benefits. Our study reveals a unique regulation of the degradation of PD-L1 in HCC, and provides an attractive therapeutic target, a potential drug, and a new prognostic marker for the clinical treatment of HCC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Spodoptera frugiperda is a highly destructive migratory pest that threatens various crops globally. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is an effective biocontrol agent against lepidopteran pests. Here, we explored the molecular mechanisms underlying the immune response to AcMNPV infection in S. frugiperda . RNA-seq and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses identified the Toll, IMD, and apoptosis pathways as primary immune responses. Investigation into AcMNPV-induced apoptosis in the S. frugiperda cell line (Sf9) revealed that the Toll pathway activated the JNK via the TRAF6 (TNF receptor-associated factor 6) adapter. In addition, AcMNPV-induced the differential expression of several host-encoded microRNAs (miRNAs), with significant negative regulatory effects, on S. frugiperda antiviral immune genes. RNAi and miRNA-mimic mediated silencing of these genes resulted in increased AcMNPV proliferation. Our findings reinforce the potential of AcMNPV as a potent biocontrol agent and further our understanding of developing biotechnology-based targeted pest control agents.

Objectives: To compare the clinical performance (retention, secondary caries, marginal adaptation, marginal discoloration, and postoperative hypersensitivity) of self-adhesive flowable composite resins (SAFCs) and flowable composite resins (FCs) in permanent teeth with occlusal cavities., Data: Randomized controlled trials (RCTs) of SAFCs versus FCs with a follow-up length of at least one year. No restrictions were placed on language or publication date., Sources: Five databases, including PubMed, Embase, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials, were searched manually by browsing ten related journals. On 14 June 2023, all electronic and manual searches were updated., Study Selection: Five RCTs with 138 participants were included. Cochrane's risk of bias tool (2.0) was implemented in selected studies, and the GRADE tool was utilised to evaluate the evidence quality. To summarize the effects of the treatments and pool the data, a random-effects model was used., Conclusions: According to the modified United States Public Health Service Evaluation (USPHS) criteria, there was no discernible difference between the groups during the two-year follow-up period (maximum follow-up time). Nevertheless, FCs applied with the etch-and-rinse mode demonstrated superior marginal adaptation and marginal discoloration at the two-year follow-up (relative risk = 3.21 [1.50 to 6.83], 3.40 [1.10, 10.48]). The evidence for marginal discoloration at any recall time and marginal adaptation at the one-year follow-up was graded as moderate quality due to inconsistency. Moreover, low-quality evidence for marginal adaptation at two-year follow-up was due to imprecision and inconsistency., Clinical Significance: SAFCs exhibited clinical performance comparable to that of FCs in occlusal cavities. Further high-quality clinical trials are needed to provide solid evidence to support the clinical application of SAFCs., Registration: PROSPERO (CRD42022374983)., Competing Interests: Declaration of Competing Interest The authors have stated explicitly that there are no conflicts of interest in connection with this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Long non-coding RNAs (lncRNAs) represent a class of RNA molecules that do not encode proteins. Generally studied for their regulatory potential in model insects, relatively little is known about their immunoregulatory functions in different castes of eusocial insects, including Solenopsis invicta , a notoriously invasive insect pest. In the current study, we used Metarhizium anisopliae , an entomopathogenic fungus, to infect the polymorphic worker castes (Major and Minor Workers) and subjected them to RNA sequencing at different intervals (6, 24, and 48 h post-infection (hpi)). Comprehensive bioinformatic analysis identified 5719 (1869 known and 3850 novel) lncRNAs in all libraries. Genomic characteristics analysis showed that S. invicta lncRNAs exhibited structural similarities with lncRNAs from other eusocial insects, including lower exon numbers, shorter intron and exon lengths, and a lower expression profile. A comparison of lncRNAs in major and minor worker ants revealed that several lncRNAs were exclusively expressed in one worker caste and remained absent in the other. LncRNAs such as MSTRG.12029.1 , XR&#95;005575440.1 (6 h), MSTRG.16728.1 , XR&#95;005575440.1 (24 h), MSTRG.20263.41 , and MSTRG.11994.5 (48 h) were only present in major worker ants, while lncRNAs such as MSTRG.8896.1 , XR&#95;005574239.1 (6 h), MSTRG.20289.8 , XR&#95;005575051.1 (24 h), MSTRG.20289.8 , and MSTRG.6682.1 (48 h) were only detected in minor workers. Additionally, we performed real-time quantitative PCR and experimentally validated these findings. Functional annotation of cis -acting lncRNAs in major worker ants showed that lncRNAs targeted genes such as serine protease , trypsin , melanization protease-1 , spaetzle-3 , etc. In contrast, apoptosis and autophagy-related genes were identified as targets of lncRNAs in minor ants. Lastly, we identified several lncRNAs as precursors of microRNAs (miRNAs), such as miR-8, miR-14, miR-210, miR-6038, etc., indicating a regulatory relationship between lncRNAs, miRNAs, and mRNAs in antifungal immunity. These findings will serve as a genetic resource for lncRNAs in polymorphic eusocial ants and provide a theoretical basis for exploring the function of lncRNAs from a unique and novel perspective.

Forensic entomology case reports are the product of rapid development in the field, the widespread acceptance of the science and the application of forensic entomological knowledge. In this study, we retrospectively summarized information derived from 307 forensic entomology case reports from 1935 to 2022 from a global perspective. Our checklist of relevant information included insect species, specific indoor or outdoor preferences, preferred temperatures, and stages of body decomposition. Finally, a concept and calculation method for postmortem interval (PMI) estimation accuracy was proposed. There were 232 cases using insect developmental data and 28 cases using succession patterns to estimate PMI. A total of 146 species of insects were involved in the cases, of which 62.3% were Diptera and 37.7% were Coleoptera. Postmortem intervals were estimated from eggs in 4 cases, larvae in 180 cases, pupae in 45 cases, and puparia in 38 cases. The majority of cases were from June to October, and the average number of species mentioned in the cases was more at 15-30 °C. Considering the standardization of application, in the majority of cases, insect evidence was collected by other personnel and sent to forensic entomologists, there was a delay in the sampling, and the scene or meteorological data were directly used without correcting. Our data shows that there are still many shortcomings in the universality and standardization of forensic entomology in its practical application., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Polyetheretherketone (PEEK) is one of the most promising implant materials for hard tissues due to its similar elastic modulus; however, usage of PEEK is still limited owing to its biological inertness and low osteoconductivity. The objective of the study was to provide PEEK with the ability to sustain the release of growth factors and the osteogenic differentiation of stem cells. The PEEK surface was sandblasted and modified with polydopamine (PDA). Moreover, successful sandblasting and PDA modification of the PEEK surface was confirmed through physicochemical characterization. The gelatin hydrogel was then chemically bound to the PEEK by adding a solution of glutaraldehyde and gelatin to the surface of the PDA-modified PEEK. The binding and degradation of the gelatin hydrogel with PEEK (GPEEK) were confirmed, and the GPEEK mineralization was observed in simulated body fluid. Sustained release of bone morphogenetic protein (BMP)-2 was observed in GPEEK. When cultured on GPEEK with BMP-2, human mesenchymal stem cells (hMSCs) exhibited osteogenic differentiation. We conclude that PEEK with a gelatin hydrogel incorporating BMP-2 is a promising substrate for bone tissue engineering.

Tumor development, involving both cell growth (mass accumulation) and cell proliferation, is a complex process governed by the interplay of multiple signaling pathways. TET2 mainly functions as a DNA dioxygenase, which modulates gene expression and biological functions via oxidation of 5mC in DNA, yet whether it plays a role in regulating cell growth remains unknown. Here we show that TET2 suppresses mTORC1 signaling, a major growth controller, to inhibit cell growth and promote autophagy. Mechanistically, TET2 functions as a 5mC "eraser" by mRNA oxidation, abolishes YBX1-HuR binding and promotes decay of urea cycle enzyme mRNAs, thus negatively regulating urea cycle and arginine production, which suppresses mTORC1 signaling. Therefore, TET2-deficient tumor cells are more sensitive to mTORC1 inhibition. Our results uncover a novel function for TET2 in suppressing mTORC1 signaling and inhibiting cell growth, linking TET2-mediated mRNA oxidation to cell metabolism and cell growth control. These findings demonstrate the potential of mTORC1 inhibition as a possible treatment for TET2-deficient tumors., (© 2023. Center for Excellence in Molecular Cell Science, CAS.)

Introduction: Pregnancy is a dynamic time period associated with significant physiological changes in the cardiovascular system. It is well known that during pregnancy, the placenta secretes a variety of molecular signals, including exosomes, into the maternal circulation to adapt to increased blood volume and maintain blood pressure at normotensive levels., Methods: In the present study, we compared the effects of exosomes derived from the peripheral blood serum of nonpregnant women (NP-Exo) and pregnant women with uncomplicated pregnancy (P-Exo) on endothelial cell function. We also analyzed the proteomic profiles of these two groups of exosomes and the molecular mechanisms underlying the effect of exosome cargoes on vascular endothelial cell function., Results: We found that P-Exo were positively involved in regulating the function of human umbilical vein endothelial cell (HUVEC) and promoting the release of nitric oxide (NO). Furthermore, we revealed that trophoblast-derived pregnancy-specific beta-1-glycoprotein 1 (PSG1)-enriched exosomes treatment induced the promotion of HUVEC proliferation and migration as well as the release of NO. In addition, we found that P-Exo maintained blood pressure at normal levels in mice., Discussion: These results suggested that PSG1-enriched exosomes derived from maternal peripheral blood regulate the function of vascular endothelial cells and play an important role in maintaining maternal blood pressure during pregnancy., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Two new tin(II) phosphates, Sn II Sn IV (PO 4 ) 2 and SrSn(PO 4 )PO 2 (OH) 2 , were synthesized by the high-temperature solution method and hydrothermal method, respectively. Theoretical study indicates that by introducing tin(II) with stereochemical activity lone pairs (SCALP) in metal phosphates, the birefringence was enhanced, 0.048@1064 nm for Sn II Sn IV (PO 4 ) 2 and 0.080@1064 nm for SrSn(PO 4 )PO 2 (OH) 2 ., (© 2023 Wiley-VCH GmbH.)

The insulin-like signaling (IIS) pathway is essential for insect growth and development. In this study, we showed that eurycomanone (EN) is an active compound with growth inhibitory activity against Spodoptera frugiperda larvae. Experiments in cells and RNA-seq analysis in the midgut showed that EN targeted the IIS pathway in S. frugiperda to activate the transcription factor SfFoxO ( S. frugiperda forkhead boxO) to regulate mRNA levels associated with nutrient catabolism. Additionally, mass spectrometry imaging revealed that EN was distributed in the larval gut and enriched in the inner membrane of the gut. Immunofluorescence, western blotting, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) results showed that EN induced program cell death (PCD) in the larvae midgut. Thus, EN targeted the insulin receptor to inhibit the IIS signaling pathway, exerting inhibitory activity on the growth and development of S. frugiperda larvae. Our results suggest that EN has great potential as a botanical pesticide, and the IIS signaling pathway may be an effective target for botanical pesticides.

Background: Transmural healing (TH) is a potential therapeutic goal of Crohn's disease (CD) and is associated with better clinical outcomes. However, few studies have described early TH and its predictors., Objectives: We aimed to evaluate early TH and its predictors using magnetic resonance enterography (MRE) in patients with CD receiving ustekinumab (UST)., Design: This was a retrospective observational study., Methods: Patients with active CD treated with UST and their intestinal segments with bowel wall thickness (BWT) ⩽ 3 mm at baseline were included. Clinical characteristics, laboratory indicators, endoscopic manifestations, and MRE indices were evaluated at baseline and week 26 (W26) of the therapy. The following MRE parameters were assessed: BWT, edema, apparent diffusion coefficient (ADC), Clermont score, Magnetic Resonance Index of Activity score, fat stranding, comb sign, and stricture. TH was defined as BWT ⩽ 3 mm without any signs of inflammation (i.e., ulceration, edema, diffusion-weighted hyperintensity, and increased contrast enhancement) at W26., Results: The study included 37 patients with 106 intestinal segments (including 15 proximal small intestines, 33 terminal ilea, and 58 colons). Clinical features, laboratory indicators, endoscopic results, and MRE parameters at W26 were significantly improved after UST treatment in both patient-based and intestinal segment-based analysis. Seven (18.9%) patients and 26 (24.5%) intestinal segments achieved TH at W26. Baseline BWT [odds ratio (OR) = 0.287, 95% confidence interval (CI), 0.090-0.918, p  = 0.035] and ADC (OR = 2.997, 95% CI, 1.009-8.908, p  = 0.048) predict TH of patients at W26. Baseline ADC (OR = 2.857, 95% CI, 1.285-6.349, p  = 0.010) and presence of stenosis (OR = 0.196, 95% CI, 0.052-0.735, p  = 0.016) were associated with TH of segments at W26., Conclusion: Early TH assessed by MRE was observed in nearly one-fifth of patients with CD and intestinal segments after UST treatment for 26 weeks. Baseline MRE indices such as BWT and presence of stenosis might negatively predict TH, while ADC might positively predict early TH., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

How cancer cells evade the therapeutic effects of immune checkpoint blockade is largely unknown. Here, we report that fibrinogen-like protein 1 (FGL1), a newly identified immune checkpoint ligand, was modified by acetylation at Lys 98 in hepatocellular carcinoma (HCC), which targeted it for proteasomal degradation. Sirtuin 2 (SIRT2) deacetylated and stabilized FGL1, thus promoting immune evasion. Notably, the SIRT2 inhibitor 2-Cyano-3-[5-(2,5-dichlorophenyl)-2-furanyl]-N-5-quinolinyl-2-propenamide (AGK2) enhanced acetylation of FGL1 and reduced FGL1 protein levels in vitro. The combination of AGK2 and programmed death ligand 1 (PD-L1) blockade effectively suppressed tumor growth and improved overall survival of mice. Furthermore, aspirin, an old drug, could directly acetylate FGL1 at Lys 98 and promote its degradation in vitro. Aspirin enhanced the immunotherapeutic efficacy, induced tumor regression, and extended the lifespan of tumor-bearing mice. Furthermore, the SIRT2/FGL1 axis was expressed in HCC specimens. Collectively, these findings unveil an acetylation-mediated regulation of FGL1, identify a potential target for HCC immunotherapy, and provide therapeutic strategies for the clinical treatment of HCC.

20E-hydroxyecdysone (20E) plays important roles in larval molting and metamorphosis in insects and is also involved in the insect innate immune response. Insect metamorphosis is a highly successful strategy for environmental adaptation and is the most vulnerable stage during which the insect is susceptible to various pathogens. 20E regulates a series of antimicrobial peptides (AMPs) through the immunodeficiency (IMD) pathway activation in Drosophila; nevertheless, whether other immune pathways are involved in 20E-regulated insect immunity is unknown. Our previous studies showed that BmMD-2A is a member of the MD-2-related lipid recognition (ML) family of proteins that are involved in the Bombyx mori innate immunity Toll signaling pathway. In this study, we further demonstrate that BmMD-2A is also positively regulated by 20E, and the BmMD-2A neutralization experiment suggested that 20E activates some downstream immune effect factors, the AMP genes against Escherichia coli and Staphylococcus aureus, through the regulation of BmMD-2A in larval metamorphosis, implying that B. mori may use the Toll-ML signaling pathway to maintain innate immune balance in the larval-pupal metamorphosis stage, which is a different innate immunity pathway regulated by 20E compared to the IMD pathway in Drosophila., (© 2022 Institute of Zoology, Chinese Academy of Sciences.)

Background: Probiotics play an important role in the host and have attracted widespread attention as an alternative to antibiotics. Arbor Acres broilers were used in the present experiment and fed different doses of compound probiotics at 1, 5, and 10 g kg -1 . The effects of compound probiotics on broiler growth performance and cecal transcriptome and metabolome were investigated., Results: We discovered 425 differentially expressed genes (DEGs; upregulated: 256; downregulated: 169) in the cecal transcriptome study. These DEGs were assigned to fat metabolic pathways, such as the peroxisome proliferator-activated receptor (PPAR) signaling pathway, according to KEGG analysis. Probiotics downregulated LPL and upregulated PPARα expression in the cecum. In metabolome analysis of the cecum of cecum, we screened 86 differential metabolites and performed KEGG enrichment analysis of these metabolites. The KEGG analysis showed that these differentially expressed metabolites were annotated to nucleotide metabolism-related pathways, such as purine metabolism. In the cecum, probiotics upregulated the content of guanine, AMP, 3'-AMP, adenylosuccinate, deoxyguanosine, and ADP-ribose, whereas they downregulated the content of 5-hydroxyisourate. Comprehensive transcriptome and metabolome analysis revealed that glycolysis, gluconeogenesis, and glycerophospholipid metabolism pathways were jointly enriched in cecum of broilers fed a probiotic-containing diet., Conclusion: This study provides valuable information for studying the regulation and gene metabolism network of probiotics on cecal metabolism in broilers. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

The cause for at least 50% of recurrent miscarriages is unclear, which is defined as unexplained recurrent miscarriages. The B7-H1 (PD-L1), a molecule of the B7 family, promotes tumor development by modulating immune evasion, and recent researchers have also attached importance to the role of B7-H3, another molecule of B7 family, in tumor. Based on the similarity between growth and immune response in tumors and pregnancy, we first explored the role of B7-H3 in unexplained recurrent miscarriages. We found reduced levels of B7-H3 in the villus tissue of unexplained recurrent miscarriage patients, and it was mainly expressed on the cell membrane of extravillous trophoblasts. Further, the HTR-8/SVneo and JEG-3 cells were selected to explore the role of B7-H3 in proliferation, apoptosis, tube formation, migration, and invasion. We found that B7-H3 regulated trophoblast migration and invasion via RhoA/ROCK2 signaling pathway. Inflammatory cytokines were detected through enzyme-linked immunosorbent assay after co-culturing with decidual natural killer cells and B7-H3-knockout JEG-3. Results showed that B7-H3 inhibited IL-8 and IP-10 secretion from the decidual natural killer cells. In a CBA/J × DBA/2 abortion-prone mice model, treatment with B7-H3-Fc protein successfully reduced the rate of embryo resorption. In conclusion, our results revealed a possible mechanism by which decreased B7-H3 on trophoblasts of unexplained recurrent miscarriages inhibited trophoblast migration and invasion and increased IL-8 and IP-10 secretion from the decidual natural killer cells. Furthermore, B7-H3 may be a promising new therapeutic target in unexplained recurrent miscarriage patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Arboviruses and symbiotic viruses can be paternally transmitted by male insects to their offspring for long-term viral persistence in nature, but the mechanism remains largely unknown. Here, we identify the sperm-specific serpin protein HongrES1 of leafhopper Recilia dorsalis as a mediator of paternal transmission of the reovirus Rice gall dwarf virus (RGDV) and a previously undescribed symbiotic virus of the Virgaviridae family, Recilia dorsalis filamentous virus (RdFV). We show that HongrES1 mediates the direct binding of virions to leafhopper sperm surfaces and subsequent paternal transmission via interaction with both viral capsid proteins. Direct interaction of viral capsid proteins mediates simultaneously invasion of two viruses into male reproductive organs. Moreover, arbovirus activates HongrES1 expression to suppress the conversion of prophenoloxidase to active phenoloxidase, potentially producing a mild antiviral melanization defense. Paternal virus transmission scarcely affects offspring fitness. These findings provide insights into how different viruses cooperatively hijack insect sperm-specific proteins for paternal transmission without disturbing sperm functions., (© 2023. The Author(s).)

Cannabis use is a worldwide issue with the development of legalization. Prenatal exposure to Δ9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, is related to affect fetal nervous system development. In our present study, we administered THC to pregnant mice from gestational day 5.5-12.5. Differences in neuronal cell composition and organization between the two groups were found by staining sections of the offspring hippocampus at PND21. In addition, RNA-seq of hippocampal tissue also suggested differences in gene expression due to THC treatment, especially significant enrichment to neurogenesis and neural differentiation. Subsequently, the effect of THC treatment on the proliferation and differentiation capacity of neural stem cells (NSCs) was confirmed. Based on the RNA-seq results, we selected the differentially expressed transcription factor MEF2C for validation. The effect of THC treatment on NSCs differentiation was found to be regulated by knocking down the expression of MEF2C in NSCs. Considering that THC is an agonist of cannabinoid receptor (CB1R), the differentiation outcome of NSC after THC treatment was significantly rescued, by pretreating with the CB1R inhibitor Rimonabant. Notably, pretreatment with Rimonabant restored the expression of MEF2C. Taken together, the present results suggested that THC regulated the MEF2C pathway through CB1R and had an impact on hippocampal neurodevelopment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Islet β-cell dedifferentiation may be the main cause of reduced insulin secretion. Angiotensin-(1-7) [Ang-(1-7)] can attenuate high glucose-induced apoptosis and dedifferentiation of pancreatic β-cell, but the specific signal transduction pathway and mechanism are not yet clear., Objectives: This study aimed to investigate the effects of Ang-(1-7) on high glucose-induced islet β-cell dedifferentiation by activating the phosphatidylinositol-3-kinase/Protein kinase B/ Forkhead box transcription factor O1 (PI3K/Akt/FoxO1) signaling pathway., Methods: The mouse islet β-cell line MIN6 cells were passaged and cultured and randomly divided into five groups: control (Con) group, high glucose (HG) group, HG with Ang-(1-7) group, HG with Ang-(1-7) and specific MasR antagonist A-779 group, and HG with Ang-(1-7) and PI3K inhibitor LY294002 group. After 48 hours, glucose-stimulated insulin secretion (GSIS) was detected by Enzyme-Linked Immunosorbent Assay (ELISA). The mRNA and protein expression levels of β-cell-specific factors (Pancreatic duodenal homeobox-1 (Pdx1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog A(MafA)) and endocrine progenitor cell-specific factors (Octamer binding transcription factor 4(Oct4), Nanog) were measured by Real Time-PCR and Western blot. The factors of protein expression levels of PI3K/Akt/FoxO1 signaling pathway (Akt, p-Akt, Fox- O1, p-FoxO1) were determined by Western blot., Results: We observed for the first time that high glucotoxicity can induce dedifferentiation of pancreatic islet β-cell, causing a decrease in insulin secretion levels and expression of Pdx1, MafA, p-- FoxO1, and p-Akt and an increase in expression of Oct4 and Nanog. After Ang-(1-7) intervention, insulin secretion levels and expression of Pdx1, MafA, p-FoxO1 and p-Akt were increased, and the levels of Oct4 and Nanog were reduced. However, A-779 and LY294002 could reverse this effect. During these processes, the total Akt and total FoxO1 expression did not change significantly., Conclusion: Ang-(1-7) may prevent high glucose-induced pathological dedifferentiation of pancreatic β-cell by activating the PI3K/Akt/FoxO1 signaling pathway., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In group decision making (GDM), to facilitate an acceptable consensus among the experts from different fields, time and resources are paid for persuading experts to modify their opinions. Thus, consensus costs are important for the GDM process. Notwithstanding, the unit costs in the common linear cost functions are always fixed, yet experts will generally express more resistance if they have to make more compromises. In this study, we use the quadratic cost functions, the marginal costs of which increase with the opinion changes. Aggregation operators are also considered to expand the applications of the consensus methods. Moreover, this paper further analyzes the minimum cost consensus models under the weighted average (WA) operator and the ordered weighted average (OWA) operators, respectively. Corresponding approaches are developed based on strictly convex quadratic programming and some desirable properties are also provided. Finally, some examples and comparative analyses are furnished to illustrate the validity of the proposed models., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

The effect of compound probiotics on the caecum of broilers under heat stress was assessed in this study. A total of 400 twenty-eight-day-old AA male broilers were randomly divided into 4 treatment groups, where each group had 5 replicates of 20 broilers. The 4 treatment groups were a heat stress control group (broilers receiving a normal diet) and groups HP I, HP II, and HP Ⅲ, consisting of broilers receiving 1, 5, and 10 g of compound probiotics added to each kilogram of feed, respectively. Compound probiotics (L. casei, L. acidophilus, and B. lactis at a ratio of 1:1:2) were used to formulate a compound probiotic powder, with 1 × 10 10 CFU/g of effective viable bacteria. Heat stress treatment was performed at 32 ± 1°C from 9:00 to 17:00 every day from 28 d to 42 d. In d 28 to 42, compared with the HC group, the ADG of broilers in the HP II and III groups was significantly increased (P < 0.05); the ADFI difference between groups was not significant (P > 0.05); the FCR of HP II and III broilers was significantly decreased (P < 0.05); and the FCR of the HP I group increased, but the difference was not significant (P > 0.05). Transcriptome results demonstrate that 665 differential genes were screened (DEGs; upregulated: 366, downregulated: 299). The DEGs were enriched in the B cell receptor signaling pathway, the intestinal immune network for IgA synthesis, the Fc epsilon RI signaling pathway, and other signaling pathways, according to KEGG enrichment analysis. Metabolome analysis identified 92 differential metabolites (DAMs; upregulated: 48, downregulated: 44). KEGG enrichment analysis indicated significant enrichment of Pantothenate and CoA biosynthesis and beta-Alanine metabolism. The combined transcriptome and metabolome analysis revealed that the DAMs and DEGs were mostly involved in beta-alanine metabolism, arginine biosynthesis, amino sugar and nucleotide sugar, and alanine, aspartate, and glutamate metabolism. The results of this study suggest that the addition of compound probiotics has a positive effect on intestinal metabolites, improving the growth performance and contributing to the overall health of broilers under heat stress., Competing Interests: DISCLOSURES All authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Antimicrobial peptides (AMPs) are a class of peptides widely existing in nature with broad-spectrum antimicrobial activity. It is considered as a new alternative to traditional antibiotics because of its unique mechanism of antimicrobial activity. The development and application of natural AMPs are limited due to their drawbacks such as low antimicrobial activity and unstable metabolism. Therefore, the design and optimization of derived peptides based on natural antimicrobial peptides have become recent research hotspots. In this paper, we focus on ribosomal AMPs and summarize the design and optimization strategies of some related derived peptides, which include reasonable primary structure modification, cyclization strategy and computer-aided strategy. We expect to provide ideas for the design and optimization of antimicrobial peptides and the development of anti-infective drugs through analysis and summary in this paper.