Search

Abstract Coral reconstruction often serves as a major proxy of high-resolution sea surface temperature (SST) variability beyond the instrumental era. However, coral reconstructions are sparse and are usually studied for interannual variability, with few studies on the monthly features. In this study, we reconstruct the monthly SST spatial field by applying the paleoclimate data assimilation method to the coral records of the latest CoralHydro2k data set for the instrument period of 1880–2000. A comparison with observed SST variability shows that our assimilated tropical SST variability performs reasonably well for the seasonal cycle and monthly ENSO characteristics, notably the phase-locking and onset timing, and more realistic spatial fields relative to the model simulations. This study suggests the feasibility of applying paleoclimate data assimilation to reconstruct the monthly SST in the historical period.

Abstract Chimeric Antigen Receptor T (CAR-T) cell therapy has significantly advanced in treating B-cell acute lymphoblastic leukemia (B-ALL) and has shown efficacy in managing relapsed B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Donor-derived CAR-T cell offer both high efficacy and rapid response. Although promising results exist, current research lacks definitive evidence of long-term survival benefits for patients treated with donor-derived CAR-T therapy. We report the long-term survival of 32 patients with post-transplant relapsed B-ALL treated with donor-derived CD19 CAR-T cell, achieving either complete Remission (CR) or CR with incomplete peripheral blood recovery (CRi). The median follow-up was 42 months, with 2-year overall survival (OS) and event-free survival (EFS) rates of 56.25% and 50.0%, respectively. The 5-year OS and EFS rates were 53.13% and 46.88%, with no new long-term adverse events observed. These findings demonstrate good long-term safety, supporting donor-derived CAR-T cell as a recommended treatment option for relapsed B-ALL patients post-transplantation. Trial registration: https://www.chictr.org.cn/showproj.html?proj=14315 . Registration number: ChiCTR-OOC-16008447.

Abstract Background The comorbidity of tuberculosis (TB) and diabetes mellitus (DM) is a significant global public health issue. This study aims to explore the recurrence risk and related factors of active pulmonary TB, specifically focusing on the impact of DM. Methods A retrospective cohort study was conducted in Lianyungang City, Jiangsu Province, Eastern China by recruiting 12,509 individuals with newly diagnosed pulmonary TB between 2011 and 2019. The Cox proportional hazards models were performed to identify risk factors of recurrence and assess the association between DM and recurrence. The hazard ratio (HR) and 95% confidence interval (CI) were used to estimate the strength of the association. Results After a median follow-up period of 5.46 years, we observed 439 recurrent cases (incident recurrence rate: 6.62 per 1000 person-years). Males (HR: 1.30, 95% CI: 1.03–1.64), patients aged ≥ 60 years (HR: 1.39, 95% CI: 1.15–1.70), DM (HR: 2.40, 95% CI: 1.68–3.45), and etiologic positivity in the initial episode (HR: 2.42, 95% CI: 2.00-2.92) had a significantly increased risk of recurrence. Conclusions Recurrence of pulmonary TB patients who have completed treatment, especially those who also suffer from DM, should be a concern. Enhanced follow-up and targeted surveillance of these high-risk groups are needed.

Abstract The coherent continental-wide speleothem water isotope records are accompanied by regionally inconsistent moisture patterns within the Asian summer monsoon (ASM) region, leaving a disputed explanation of monsoonal hydroclimate variability at the orbital timescale. Here, the transient simulation forced by orbital parameters during the past 300,000 years in an isotope-enabled fully coupled model shows that the complex ASM response can be understood as a grand dipole pattern of oxygen isotope and rainfall between South Asia and Japan, with South China lying in a hybrid transition region. While the dipole monsoon rainfall change between South Asia and Japan is related to the large-scale circulation adjustment in response to Northern Hemisphere summer insolation, the dipole oxygen isotope pattern is associated with the changing contribution of moisture sources. Our results provide new clues to reconcile ASM hydroclimate patterns at orbital timescale as revealed by the water isotope records and other hydrological proxies.

Abstract Upwelling-induced productivity in the Arabian Sea infers an out-of-phase relation between the Indian summer monsoon and Northern Hemisphere summer insolation at the precession band but an in-phase relation at the obliquity band. These records contrast speleothem oxygen records showing an in-phase relation between the monsoon and summer insolation in two bands, leaving the driving mechanism for the Indian summer monsoon still unknown. Here we use an isotope-enabled Community Earth System Model, showing that the Indian summer monsoon rainfall and water isotopes respond directly to Northern Hemisphere summer insolation in two bands. This contrasts with the Arabian Sea upwelling which is weakened at precessional minimum but strengthened at obliquity maximum by a stronger northward shift of the monsoon wind due to the stronger summer insolation at precessional minimum compared with obliquity maximum. This paper resolves the longstanding question, supporting the Northern Hemisphere-driving mechanism for the Indian summer monsoon at orbital timescale.

Objective: This study aimed to develop novel soybean protein isolate （SPI）-based emulsifiers. Methods: The structure of SPI was modified by limited enzymolysis combined with glycosylation and the effects of this synergistic modification on the emulsification characteristics of SPI was studied. Results: Among the different components obtained from the SPI hydrolysate （SPIH）, the high molecular mass component （F30） exhibited the best emulsifying property. The emulsifying stability of F30-dextran conjugates obtained for 4 h was the best. Compared with SPI, SPIH and F30, the F30-dextran conjugates stabilized emulsions showed the lowest initial average particle size and the best storage stability. When the pH was close to the isoelectric point of SPI or the system was at a high salt concentration, all emulsions were unstable to cause aggregation. Compared with SPI, both SPIH and F30 stabilized emulsions had a higher aggregation degree. However, F30-dextran conjugates provided additional steric hindrance and hydrophilicity due to covalently bound dextran, which exhibited a higher resistance under adverse environmental conditions. Conclusion: Limited enzymolysis combined with glycosylation is a potential and reliable way to develop SPI-based emulsifying ingredients.

Abstract The meridional overturning circulation (MOC) in the ocean is a key player in the global climate system, while continental topography provides an essential backdrop to the system. In this study, we design a series of coupled model sensitivity experiments to investigate the influence of various mountain ranges on the global thermohaline circulation. The results highlight the influence of the Tibetan Plateau (TP) on the global thermohaline circulation. It emerges as a requisite for establishing the Atlantic MOC (AMOC) and a determining factor for the cessation of the Pacific MOC (PMOC). Additionally, the Antarctic continent plays a vital role in facilitating the TP to form the AMOC. While the formation of the AMOC cannot be attributed to any single mountain range, the TP alone can inhibit the PMOC’s development. By modifying the global hydrological cycle, the TP is likely to have been crucial in molding the global thermohaline circulation.

Aspergillus flavus A5P1 was used as raw material to prepare biosorbent A5P1acid by hydrochloric acid modification，which was used to adsorb acid blue 25（AB25） dyes. Batch experiments were used to explore different influencing factors. The results showed that the optimum amount of adsorbent and pH for dye adsorption was 0.5 g/L and 2，and the adsorption reached equilibrium in 60 min. Compared with unmodified adsorbents，the adsorption capacity of acid modified adsorbents increased from 137 mg/g to 182 mg/g，and the dye removal rate increased to 32%. The thermodynamics，kinetics and adsorption isotherm of AB25 removed by A5P1acid adsorption were studied. The adsorption process met the quasi-second-order kinetic model，and the adsorption rate was controlled by chemical adsorption. Moreover， it met the Freundlich adsorption isotherm，and the adsorption belonged to multi-layer heterogeneous adsorption. The thermodynamic results showed that it was an endothermic spontaneous adsorption process. The results of Zeta potential and FTIR showed that the adsorption was assigned to the electrostatic adsorption and hydrogen bonding of various functional groups. The adsorbent still retained 50.6% of the initial adsorption capacity after cyclic adsorption-desorption for 7 times. The experimental results showed that A5P1acid was a green and effective biological adsorbent material which could be used to remove anionic dyes.

Surface topography filtering is a commonly used technique in various fields, and over the years, a variety of filters have been included in international standards. However, traditional filtering methods continue to suffer from significant fitting errors in the separation of surface topography (form, waviness and roughness). To address these issues, this study proposes a new filter algorithm based on an improved VMD method that incorporates some VME algorithm ideas. The proposed filter analyzes surface topography through three pivotal steps: Firstly, it derives the optimal robust weighting function. Secondly, it integrates the weighting function into the isotropic residual constraint VMD to decompose the surface into several isotropic modes (sub-surfaces). Ultimately, it quantitatively computes and combines the sub-surfaces to reconstruct the topography of each surface. Numerical simulation experiments illustrate that the proposed algorithm outperforms advanced surface filters, significantly reducing fitting errors of surface topography separation including areal-VMD-based filters. Finally, two grinding workpieces are analyzed using the proposed algorithm to demonstrate its effectiveness in evaluating machined surfaces, revealing the analytical process and presenting the results.

A high-efficiency laser coherent combination method based on the virtue of the self-transverse acceleration effect of Airy beams is proposed and demonstrated by converting an array of Gaussian beams into Airy beams array to reduce laser beams separation distance. The coherent combination procedures of circular array for both Airy and Gaussian beams are theoretically and experimentally studied. The results show that the central intensity of the laser coherent combination of the circular array of Airy beams is 14.33 times higher than that of the Gaussian beams array, and the combined efficiency of the circular array of Airy beams is 1.64 times higher than that of the Gaussian beams circular array. The method may provide an efficient way to increase combination efficiency of laser coherent combination array and may have a broad application prospect in optical communication, particle capture, material processing.

Abstract Background Smoking is a well-recognized risk factor for esophageal carcinoma, but the underlying molecular mechanism remains unclear. Previous studies have demonstrated the predictive value of non-coding RNA (ncRNA) for the prognosis of esophageal carcinoma; however, the expression of smoking-related ncRNAs has not been systematically characterized. Herein, we comprehensively assessed the hazard of heavy smoking and its impact on ncRNA expression patterns in patients with esophageal carcinoma. Methods Transcriptome and clinical features of patients with esophageal carcinoma were acquired from The Cancer Genome Atlas (TCGA) database. Cox regression analysis was employed to calculate the hazard ratio (HR) of smoking behavior. Differential expression analysis was conducted with the “edgeR” package. The smoking-related RNA regulatory network was based on lncRNA‒miRNA and miRNA‒mRNA pairs and visualized by Cytoscape 3.7.1. We applied Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for functional annotation. Univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used for model construction. We applied Kaplan‒Meier analysis with a log-rank test for survival analysis, with group comparison by the Wilcoxon signed ranked test. Results Heavy smoking contributed to the poor overall survival of esophageal carcinoma, with an HR of 3.167 (95% CI: 1.077–9.312). A total of 195 lncRNAs and 73 miRNAs were differentially expressed between patients with or without smoking behavior. We constructed smoking-related RNA regulatory networks, and functional annotation enriched a series of cancer-related pathways. We generated a smoking-related prognostic risk score and found that patients with a high score had a poor prognosis. Fourteen out of 23 immune cell types differentially infiltrated into a distinct risk group, while no correlation was observed between the risk score and immune cells. Conclusion Altogether, we profiled smoking-related ncRNA expression patterns and constructed an RNA regulatory network, providing a landscape of smoking-related molecular mechanisms of esophageal carcinoma. The smoking-related risk score, which was related to prognosis, revealed that tobacco smoking could suppress tumor immunity via the ncRNA mechanism.

Abstract. Background:. Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Here, we tried to identify the effects of the axon guidance factor semaphorin-3F (SEMA3F) on rituximab resistance as well as its therapeutic value in DLBCL. Methods:. The effects of SEMA3F on the treatment response to rituximab were investigated by gain- or loss-of-function experiments. The role of the Hippo pathway in SEMA3F-mediated activity was explored. A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects. The prognostic value of SEMA3F and TAZ (WW domain-containing transcription regulator protein 1) was examined in the Gene Expression Omnibus (GEO) database and human DLBCL specimens. Results:. We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen. Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity (CDC) activity induced by rituximab. We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20. Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter. Moreover, in patients with DLBCL, SEMA3F expression was negatively correlated with TAZ, and patients with SEMA3F lowTAZ high had a limited benefit from a rituximab-based strategy. Specifically, treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo. Conclusion:. Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.

Abstract Chimeric antigen receptor (CAR)-NK cell therapy has the advantages of a low incidence of side effects and a low cost. However, the clinical outcomes are not satisfactory due to limited antitumor effects and a limited proliferative capacity. Recently, progress in CAR-NK cell therapy has been made in NK cell engineering, target design and combination with other agents to treat relapsed or refractory hematological malignancies, especially acute myeloid leukemia and multiple myeloma. This correspondence summarizes the preclinical and clinical updates for universal CAR-NK cell therapy reported at the ASH 2022 annual meeting.

For the requirements of the multi-means observation and emergency monitoring of space objects, including space debris and near-earth asteroids, this paper analyzes the astronomical observation conditions in the stratosphere, which is the region of the earth’s atmosphere between 18 km and 55 km of altitude. The results reveal that near space has a significantly superior sky background and observation environment than ground-based observation, with the values of transmittance in the visible band and near-infrared bands more than 0.91 and 0.988, respectively. The sky background radiance at 20 km is 2.5% of the ground in the visible band and near-infrared band, which is practical for daytime observation, and there is an advantage in the availability of observable hours without the influence of aerosols and turbulence, etc. Based on near-space aerostats, such as a high-altitude balloon, a new method of space object floating observation has been proposed, including the observation facilities and scheme. The simulation shows that it has an all-weather/all-day ability while adopting multi-band observation. Applying a telescope with 9.5 mag detective ability located on the aerostat, debris with the size of about 0.36 m can be observed at a 1000 km distance and phase angle of 100°, while the near-earth asteroid with the size of about 980 km can be observed at a 5 million km distance and phase angle of 40° during the daytime. With these advantages, the aerostat-based observation would be a beneficial supplement to the ground-based observation network.

An abnormal level of dopamine (DA), a kind of neurotransmitter, correlates with a series of diseases, including Parkinson’s disease, Willis-Ekbom disease, attention deficit hyperactivity disorder, and schizophrenia. Hence, it is imperative to achieve a precise, rapid detection method in clinical medicine. In this study, we synthesized nanocomposite carbon aerogels (CAs) doped with iron and iron carbide, based on algae residue-derived biomass materials, using Fe(NO3)3 as the iron source. The modified glassy carbon electrode (GCE) for DA detection, denoted as CAs-Fe/GCE, was prepared through surface modification with this composite material. X-ray photoelectron spectroscopy and X-ray diffraction characterization confirmed the successful doping of iron into the as-prepared CAs. Additionally, the electrochemical behavior of DA on the modified electrode surface was investigated and the results demonstrate that the addition of the CAs-Fe promoted the electron transfer rate, thereby enhancing their sensing performance. The fabricated electrochemical DA biosensor exhibits an accurate detection of DA in the concentration within the range of 0.01~200 µM, with a detection limit of 0.0033 µM. Furthermore, the proposed biosensor is validated in real samples, showing its high applicability for the detection of DA in beverages.

Background Lack of tumor-infiltrating T lymphocytes and concurrent T-cell dysfunction have been identified as major contributors to glioblastoma (GBM) immunotherapy resistance. Upregulating CXCL10 in the tumor microenvironment (TME) is a promising immunotherapeutic approach that potentially increases tumor-infiltrating T cells and boosts T-cell activity but is lacking effective delivery methods.Methods In this study, mesenchymal stem cells (MSCs) were transduced with a recombinant lentivirus encoding Cxcl10, Nrf2 (an anti-apoptosis gene), and a ferritin heavy chain (Fth) reporter gene in order to increase their CXCL10 secretion, TME survival, and MRI visibility. Using FTH-MRI guidance, these cells were injected into the tumor periphery of orthotopic GL261 and CT2A GBMs in mice. Combination therapy consisting of CXCL10-Nrf2-FTH-MSC transplantation together with immune checkpoint blockade (ICB) was also performed for CT2A GBMs. Thereafter, in vivo and serial MRI, survival analysis, and histology examinations were conducted to assess the treatments’ efficacy and mechanism.Results CXCL10-Nrf2-FTH-MSCs exhibit enhanced T lymphocyte recruitment, oxidative stress tolerance, and iron accumulation. Under in vivo FTH-MRI guidance and monitoring, peritumoral transplantation of CXCL10-Nrf2-FTH-MSCs remarkably inhibited orthotopic GL261 and CT2A tumor growth in C57BL6 mice and prolonged animal survival. While ICB alone demonstrated no therapeutic impact, CXCL10-Nrf2-FTH-MSC transplantation combined with ICB demonstrated an enhanced anticancer effect for CT2A GBMs compared with transplanting it alone. Histology revealed that peritumorally injected CXCL10-Nrf2-FTH-MSCs survived longer in the TME, increased CXCL10 production, and ultimately remodeled the TME by increasing CD8+ T cells, interferon-γ+ cytotoxic T lymphocytes (CTLs), GzmB+ CTLs, and Th1 cells while reducing regulatory T cells (Tregs), exhausted CD8+ and exhausted CD4+ T cells.Conclusions MRI-guided peritumoral administration of CXCL10 and Nrf2-overexpressed MSCs can significantly limit GBM growth by revitalizing T lymphocytes within TME. The combination application of CXCL10-Nrf2-FTH-MSC transplantation and ICB therapy presents a potentially effective approach to treating GBM.

Epitranscriptome studies have shown that critical RNA modifications drive tumorigenicity; however, the role of 5-methylcytosine (m5C) RNA methylation remains poorly understood. We extracted 17 m5C regulators and clustered distinct m5C modification patterns by consensus clustering analysis. Gene set variation and single-sample gene set enrichment analysis were applied to quantify functional analysis and immune infiltration. The least absolute shrinkage and selection operator was employed to develop a prognostic risk score. Kaplan-Meier with log-rank test was used for survival analysis. Differential expression analysis was performed with the “limma” R package. Wilcoxon signed ranked test or Kruskal-Wallis test was used to compare groups. We observed that m5C RNA methylation was commonly upregulated in gastrointestinal cancer and related to prognosis. Clusters were identified for m5C patterns, with distinct immune infiltrations and functional pathways. The risk scores of m5C regulators were independent risk factors. Differentially expressed mRNAs (DEmRNAs) in m5C clusters were involved in cancer-related pathways. The methylation-based m5Cscore showed a significant effect on the prognosis. Patients with a lower m5Cscore exhibited more therapeutic efficiency on anti-CTLA4 therapy in liver cancer, while the combination of anti-CTLA4 therapy and pd1 was more efficient for patients with a lower m5Cscore in pancreatic cancer. We uncovered dysregulations of m5C-related regulators in gastrointestinal cancer and their associations with overall survival. Some immune cells were differently infiltrated in distinct m5C modification patterns, indicating their potential impacts on gastrointestinal cancer cell-immune. Moreover, an m5Cscore, derived from DEmRNAs in specific clusters, can serve as a classifier for immunotherapy.

Abstract The Atlantic meridional overturning circulation (AMOC) is predicted to weaken under global warming. Whether it is caused by heat flux or freshwater flux is under debate. Here we separate these two processes in changing the AMOC under global warming. The simulated AMOC is weakened during the first 600 years and then gradually recovered to its initial state, with heat flux and freshwater feedback dominating at different timescales. Global warming immediately puts freshwater into the Southern Ocean, which triggers the initial AMOC weakening via altering surface temperature. Concurrently, the extensive heat into the ocean surface increases the temperature over the subpolar North Atlantic, reducing the deep convection and thus the AMOC in the subsequent 50–150 years. Meanwhile, the Arctic sea ice melt leads to the AMOC shutdown. Subsequently, the salinity accumulation in the subtropical North Atlantic propagating northward to restart the North Atlantic deep convection is responsible for the AMOC recovery.

Abstract Background Fibroblast growth factors (FGFs) and their receptors (FGFRs) play a crucial role in cell fate and angiogenesis, with dysregulation of the signaling axis driving tumorigenesis. Therefore, many studies have targeted FGF/FGFR signaling for cancer therapy and several FGFR inhibitors have promising results in different tumors but treatment efficiency may still be improved. The clinical use of immune checkpoint blockade (ICB) has resulted in sustained remission for patients. Main Although there is limited data linking FGFR inhibitors and immunotherapy, preclinical research suggest that FGF/FGFR signaling is involved in regulating the tumor microenvironment (TME) including immune cells, vasculogenesis, and epithelial-mesenchymal transition (EMT). This raises the possibility that ICB in combination with FGFR-tyrosine kinase inhibitors (FGFR-TKIs) may be feasible for treatment option for patients with dysregulated FGF/FGFR signaling. Conclusion Here, we review the role of FGF/FGFR signaling in TME regulation and the potential mechanisms of FGFR-TKI in combination with ICB. In addition, we review clinical data surrounding ICB alone or in combination with FGFR-TKI for the treatment of FGFR-dysregulated tumors, highlighting that FGFR inhibitors may sensitize the response to ICB by impacting various stages of the “cancer-immune cycle”.

Abstract Objectives Identifying prognostic factors helps optimize the treatment regimen and promote favorable outcomes. We conducted a prospective cohort study on patients with pulmonary tuberculosis to construct a clinical indicator-based model and estimate its performance. Methods We performed a two-stage study by recruiting 346 pulmonary tuberculosis patients diagnosed between 2016 and 2018 in Dafeng city as the training cohort and 132 patients diagnosed between 2018 and 2019 in Nanjing city as the external validation population. We generated a risk score based on blood and biochemistry examination indicators by the least absolute shrinkage and selection operator (LASSO) Cox regression. Univariate and multivariate Cox regression models were used to assess the risk score, and the strength of association was expressed as the hazard ratio (HR) and 95% confidence interval (CI). We plotted the receiver operating characteristic (ROC) curve and calculated the area under the curve (AUC). Internal validation was conducted by 10-fold cross-validation. Results Ten significant indicators (PLT, PCV, LYMPH, MONO%, NEUT, NEUT%, TBTL, ALT, UA, and Cys-C) were selected to generate the risk score. Clinical indicator-based score (HR: 10.018, 95% CI: 4.904–20.468, P

Background: To explore the difference and diagnostic value evaluation of serum tumor markers in different clinical stages of elderly non-small cell lung cancer (NSCLC) patients. Methods: Select 100 elderly NSCLC patients admitted to our hospital from June 2018 to June 2021, collect the general data, pathology data and imaging data of the patients, and the patients were divided into I-IV clinical stages according to the International Union Against Cancer (UICC) 8th edition lung cancer TNM staging standard. Detect the subjects' peripheral serum tumor markers, serum carcinoembryonic antigen (CEA), cytokeratin fragment 21-1 (CYFRA21-1), squamous cell carcinoma-associated antigen (SCCA), carbohydrate antigen 125 (CA125) and sugar Class antigen 199 (CA199). Compare the differences of serum CEA, CYFRA21-1, SCCA, CA125, CA199 levels in different clinical stages of elderly NSCLC patients, and the diagnostic value of the above indicators for elderly NSCLC patients was analyzed by receiver operating characteristic curve (ROC curve) and area under the curve (AUC). Results: The smoking history, differentiation degree, lymph node metastasis and tumor diameter of elderly NSCLC patients with different clinical stages are significantly different; with the increase of NSCLC disease progression, the levels of serum CEA, CYFRA21-1, SCCA, CA125, and CA199 continue to increase, in serum. There is a significant correlation between the markers; serum CEA, CYFRA21-1, SCCA, CA125, CA199 have diagnostic value for the clinical staging of elderly NSCLC patients. Conclusion: The elevation of serum CEA, CYFRA21-1, SCCA, CA125 and CA199 in elderly NSCLC patients is positively correlated with the degree of tumor malignancy. The detection of the above indicators is of great value for the early diagnosis and disease monitoring of elderly NSCLC.

Acquired immunodeficiency syndrome (AIDS) cannot be completely cured, mainly due to the existence of a latent HIV-1 reservoir. However, our current understanding of the molecular mechanisms underlying the establishment and maintenance of HIV-1 latent reservoir is not comprehensive. Here, using a genome-wide CRISPR-Cas9 activation library screening, we identified E3 ubiquitin ligase F-box protein 34 (FBXO34) and the substrate of FBXO34, heterogeneous nuclear ribonucleoprotein U (hnRNP U) was identified by affinity purification mass spectrometry, as new host factors related to HIV-1 latent maintenance. Overexpression of FBXO34 or knockout of hnRNP U can activate latent HIV-1 in multiple latent cell lines. FBXO34 mainly promotes hnRNP U ubiquitination, which leads to hnRNP U degradation and abolishment of the interaction between hnRNP U and HIV-1 mRNA. In a latently infected cell line, hnRNP U interacts with the ReV region of HIV-1 mRNA through amino acids 1-339 to hinder HIV-1 translation, thereby, promoting HIV-1 latency. Importantly, we confirmed the role of the FBXO34/hnRNP U axis in the primary CD4+ T lymphocyte model, and detected differences in hnRNP U expression levels in samples from patients treated with antiretroviral therapy (ART) and healthy people, which further suggests that the FBXO34/hnRNP U axis is a new pathway involved in HIV-1 latency. These results provide mechanistic insights into the critical role of ubiquitination and hnRNP U in HIV-1 latency. This novel FBXO34/hnRNP U axis in HIV transcription may be directly targeted to control HIV reservoirs in patients in the future.

Abstract Background Dyslipidemia contributes to an increased risk of carotid atherosclerosis. However, the association between the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) and carotid plaque formation has not been well documented. This study aims to assess the role of LDL-C/HDL-C in the risk of carotid plaque formation in a Chinese population. Methods We followed 2,191 participants who attended the annual routine health examination. Cox proportional hazards regression, restricted cubic spline (RCS), and subgroup analysis were applied to evaluate the association between the LDL-C/HDL-C ratio and carotid plaques. The hazard ratio (HR) and 95% confidence interval (CI) were used to estimate the strength of the association. Results Among 2,191 participants, 388 had incident carotid plaques detected, with a median follow-up time of 1.05 years. Compared with subjects younger than 45 years, those aged 45 to 59 years (HR: 2.00, 95% CI: 1.55–2.58) and over 60 years (HR: 3.36, 95% CI: 2.47–4.58) had an increased risk of carotid plaque formation. Males (HR: 1.26, 95% CI: 1.01–1.56), diabetes (HR: 1.46, 95% CI: 1.06–2.01) and a high LDL-C/HDL-C ratio (HR: 1.22, 95% CI: 1.07–1.38) were significantly linked with the occurrence of carotid plaques. After adjusting for potential confounding factors, we observed that a high LDL-C/HDL-C ratio promoted carotid plaque events (HR: 1.30, 95% CI: 1.12–1.50). The RCS analysis revealed a significant nonlinear association. The association was stronger among females (P-interaction

Abstract Background The mining of new allelic variation and the induction of new genetic variability are the basis for improving breeding efficiency. Results In this study, in total, 3872 heavy ion-irradiated M2 generation rice seeds and individual leaves were collected. The grain length was between 8 and 10.22 mm. The grain width was between 1.54 and 2.87 mm. The results showed that there was extensive variation in granulotype. The allelic variation in GS3 and GW5 was detected in 484 mixed samples (8:1) using targeted sequencing technology, and 12 mixed samples containing potential mutations and 15 SNPs were obtained; combined with Sanger sequencing and phenotype data, 13 key mutants and their corresponding SNPs were obtained; protein structural and functional analysis of key mutants screened out 6 allelic variants leading to altered grain shape, as well as the corresponding mutants, including long-grain mutants GS3-2 and GS3-7, short-grain mutants GS3-3 and GS3-5, wide-grain mutant GW5-1 and narrow-grain mutant GW5-4; whole genome sequencing identified new grain length gene allelic variants GS3-G1, GS3-G2 and GS3-G3. Conclusion Based on the above studies, we found 6 granulotype mutants and 9 granulotype-related allelic variants, which provided new functional gene loci and a material basis for molecular breeding and genotype mutation and phenotype analysis. We propose a method for targeted identification of allelic variation in rice grain type genes by combining targeted sequencing of mixed samples and whole genome sequencing. The method has the characteristics of low detection cost, short detection period, and flexible detection of traits and genes.

In order to obtain highly accurate infrared spectra, the optical path scanning control system in a portable Fourier transform spectrometer (FTS) must be able to realize highly stable reciprocal scanning. To address the positional localization and speed fluctuation problems of optical path scanning control systems, an adaptive feedforward–nonlinear PI cascade composite control algorithm (AF-NLPI) is proposed. A physical model of an optical path scanning control system is established. Moreover, an adaptive feedforward compensator using a dynamic forgetting factor is proposed, and it was combined with a nonlinear PI cascade controller to form a composite controller. The control parameters were tuned using the atomic orbital search algorithm. Further, the simulation and experimental results demonstrate that the AF-NLPI can effectively improve the control accuracy and anti-interference ability of an optical path scanning control system in a portable FTS with high feasibility and practicality. By setting the scanning stroke of the system to 8 mm and scanning at 10 mm/s, the stability of the optical scanning speed reached 99.47% when controlled by the controller proposed in this paper, thus fulfilling the motion requirements for optical path scanning control systems.

Objective: This study aimed to provide strategy for controlling the fungal diseases of postharvest blueberry in Sichuan province. Methods: The pathogenic bacteria from 14 planting bases in Sichuan Province were isolate, identified, pathogenicity determination. Moreover, the effects of temperature and light on mycelia growth of the dominant and subdominant strains of blueberry after harvest were studied, and the effective natural antibacterial components against them were screened. Results: The blueberry postharvest rot diseases were caused by the following nine kinds of fungi: Aspergillus niger, Aspergillus tubingensis, Neofusicoccum parvum, Neopestalotiopsis sp., Fusarium graminearum, Alternaria alternata, Mucor fragilis, Penicillium sp., Cladosporium xylophilum. Aspergillus niger was the dominant species with the highest isolation frequency and the most pathogenic, and Neopestalotiopsis sp., Alternaria alternata, Penicillium sp., Cladosporium xylophilum were the subdominant species with isolation frequencies greater than 10%. The optimum growth temperature ranged from 20 ℃to 35 ℃of dominant and subdominant strains of blueberry postharvest. The effects of light on the mycelia growth of A. niger，Neopestalotiopsis sp., A. alternata, and C. xylophilum were significant，but that was insignificant on the growth of Penicillium sp. strains. Thymol showed good broad-spectrum antibacterial activity, the EC50 values of dominant and subdominant strains of blueberry postharvest was 30~50 mg/L, while the thymol applied directly to blueberry postharvest fungal control in aqueous solution should not be higher than 50 mg/L. Conclusion: Thymol is more effective on postharvest diseases of blueberry in Sichuan province.

Abstract Background Diabetic foot ulcer is one of the major complications for patients with diabetes, and has become an important cause of non-traumatic amputation. Necrotizing fasciitis is a life-threatening soft-tissue infection involving the fascia and subcutaneous tissue. When diabetic foot ulcers are complicated by necrotizing fasciitis (DNF), this increases the risk for amputation and mortality, making DNF treatment more complicated, and eventually leading to amputation and mortality. However, studies on pathogenic bacteria’s distribution and drug sensitivity in DNF patients remain lacking. This study investigated the distribution and susceptibility of pathogenic bacteria in DNF patients, and provided empirical antibacterial guidance for the clinic. Methods In a single diabetic foot center, the results from microbial cultures and drug susceptibility tests of patients with DNF from October 2013 to December 2020 were collected and analyzed. Results A total of 101 DNF patients were included in this study, of whom 94 had positive culture test results. A total of 124 pathogens were cultured, including 76 Gram-positive bacterial strains, 42 Gram-negative bacterial strains, and six fungal strains. Polymicrobial infections accounted for 26.7% and monomicrobial infections accounted for 66.3%. Staphylococcus aureus was the most common bacterium isolated, followed by Enterococcus faecalis and Streptococcus agalactiae. Pseudomonas aeruginosa, Klebsiella pneumoniae, and Proteus mirabilis were the most common Gram-negative bacteria. Thirty-five strains of multi-drug resistant bacteria were isolated, representing 28.2% of the total isolates. Gram-positive bacteria were more sensitive to levofloxacin, moxifloxacin, vancomycin, teicoplanin, tigecycline, and linezolid, while Gram-negative bacteria were more sensitive to amikacin, piperacillin/tazobactam, cefoperazone/sulbactam, ceftazidime, cefepime, imipenem, and meropenem. Conclusions Gram-positive bacteria were the main bacteria isolated from DNF patients. The bacterial composition, the proportion of multi-drug resistant bacteria among the pathogens, and the high risk for amputation should be fully considered in the initial empirical medication, and broad-spectrum antibacterials are recommended.

ObjectiveUsing serum screening test and simulated gastrointestinal fluid digestion stability test to explore whether Oryza sativa recombinant human serum albumin (OsrHSA) has potential allergenicity.MethodsIn this study, 75 serum samples from patients with allergies to shrimp, wheat, house dust mites, eggs and milk, which containing specific IgE antibody concentrations greater than 3.5 kUA/L, as well as 4 healthy human serum samples were selected. Enzyme-linked immunosorbent assay was used to investigate whether OsrHSA could bind to allergen-specific IgE antibodies in the serum. The digestive stability test of the simulated gastrointestinal fluid of OsrHSA protein was carried out in accordance with the national food safety standard, detection of genetically modified organisms and derived products-simulated gastrointestinal fluid digestion stability test.ResultsThree sera allergic to milk had immunological cross-reactions with OsrHSA, indicating that the protein might have antigenic intersection with milk allergens. OsrHSA was completely digested within 15 s in the simulated gastric and intestinal fluid, indicating that the protein was easily digested.ConclusionOsrHSA has low potential allergenicity and people who are allergic to milk needs consideration.

BackgroundDespite great success, immunotherapy still faces many challenges in practical applications. It was previously found that family with sequence similarity 110 member A (FAM110A) participate in the regulation of the cell cycle and plays an oncogenic role in pancreatic cancer. However, the prognostic value of FAM110A in pan-cancer and its involvement in immune response remain unclear.MethodsThe Human Protein Atlas (HPA) database was used to detect the expression of FAM110A in human normal tissues, the Tumor Immune Estimation Resource (TIMER) and TIMER 2.0 databases were used to explore the association of FAM110A expression with immune checkpoint genes and immune infiltration, and the Gene Set Cancer Analysis (GSCA) database was used to explore the correlation between FAM110A expression and copy number variations (CNV) and methylation. The LinkedOmics database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Statistical analysis and visualization of data from the The Cancer Genome Atlas (TCGA) or the Genotype–Tissue Expression (GTEx) databases were performed using the R software (version 3.6.3). Clinical samples were validated using immunohistochemistry.ResultsFAM110A expression was elevated in most tumor tissues compared with that in normal tissues. CNV and methylation were associated with abnormal FAM110A mRNA expression in tumor tissues. FAM110A affected prognosis and was associated with the expression of multiple immune checkpoint genes and abundance of tumor-infiltrating immune cells across multiple types of cancer, especially in liver hepatocellular carcinoma (LIHC). FAM110A-related genes were involved in multiple immune-related processes in LIHC.ConclusionFAM110A participates in regulating the immune infiltration and affecting the prognosis of patients in multiple cancers, especially in LIHC. FAM110A may serve as a prognostic and immunological biomarker for human cancer.

Peroxisome proliferator-activated receptor alpha (PPARA) has been suggested as a therapeutic target for chronic lymphocytic leukemia (CLL). However, the underlying molecular mechanism remains largely unclear. In this study, we analyzed DNA next-generation sequencing (NGS) data and clinical information from 86 CLL patients to identify gene markers related to treatment-free survival (TFS) length. We then constructed a genetic network that includes CLL promoters, treatment targets, and TFS-related marker genes. To assess the significance of PPARA within the network, we utilized degree centrality (DC) and pathway enrichment score (EScore). Clinical and NGS data revealed 10 TFS length-related gene markers, including RPS15, FOXO1, FBXW7, KMT2A, NOTCH1, GNA12, EGR2, GNA13, KDM6A, and ATM. Through literature data mining, 83 genes were identified as CLL upstream promoters and treatment targets. Among them, PPARA exhibited a stronger connection to CLL and TFS-related gene markers, as evidenced by its ranking at No. 13 based on DC, compared to most of the other promoters (>84%). Additionally, PPARA co-functions with 70 out of 92 in-network genes in various functional pathways/gene groups related to CLL pathology, such as regulation of cell adhesion, inflammation, reactive oxygen species, and cell differentiation. Based on our findings, PPARA is considered one of the critical genes within a large genetic network that influences the prognosis and TFS of CLL through multiple pathogenic pathways.

Intracellular bacterial endosymbionts of arthropods are mainly transmitted vertically from mother to offspring, but phylogenetically distant insect hosts often harbor identical endosymbionts, indicating that horizontal transmission from one species to another occurs in nature. Here, we investigated the parasitoid Encarsia formosa-mediated horizontal transmission of the endosymbiont Rickettsia between different populations of whitefly Bemisia tabaci MEAM1. Rickettsia was successfully transmitted from the positive MEAM1 nymphs (R+) into E. formosa and retained at least for 48 h in E. formosa adults. Fluorescence in situ hybridization (FISH) visualization results revealed that the ovipositors, mouthparts, and digestive tract of parasitoid adults get contaminated with Rickettsia. Random non-lethal probing of Rickettisia-negative (R−) MEAM1 nymphs by these Rickettsia-carrying E. formosa resulted in newly infected MEAM1 nymphs, and the vertical transmission of Rickettsia within the recipient females can remain at least up to F3 generation. Further phylogenetic analyses revealed that Rickettsia had high fidelity during the horizontal transmission in whiteflies and parasitoids. Our findings may help to explain why Rickettsia bacteria are so abundant in arthropods and suggest that, in some insect species that shared the same parasitoids, Rickettsia may be maintained in populations by horizontal transmission.

Extranodal NK/T-cell lymphoma (ENKTL) is a highly aggressive and heterogeneous disease with poor clinical outcome. Our previous work had demonstrated that circulating tumor DNA (ctDNA) analyses were feasible in ENKTL, and dynamic tracing of ctDNA could be used to monitor the disease status. However, the prognostic value of ctDNA in ENKTL has not been fully investigated. Patients with newly diagnosed ENKTL from February 2017 to December 2021 (n = 70) were enrolled. The pretreatment ctDNA concentration (hGE/mL) was measured. The prognostic value of ctDNA, international prognostic index (IPI), Korean prognostic index (KPI), PINK-E, and the combination of PINK-E and ctDNA (PINK-EC) were investigated in our cohort. The IPI and PINK-E risk categories had a significant difference in progression-free survival (PFS) and overall survival (OS) between the low-risk and intermediate-risk groups. The KPI risk category had a difference in PFS and OS between the intermediate-risk and high-risk groups. Furthermore, integrating ctDNA into the PINK-E model could overcome the shortcomings of other prognostic models, which could significantly distinguish the different-risk groups. Overall, our results demonstrated that PINK-EC showed a superior prognostic prediction value and stability compared with IPI, KPI, and PINK-E. The integration of molecular features of the tumor into classic risk categories might better characterize a high-risk group where novel treatment approaches are most needed.

The southeast of the Anza Basin in Kenya, located in the East African Rift System, has developed a very thick Mesozoic and Cenozoic sedimentary cover. However, the low level of exploration in this area restricts us from understanding its structural system and evaluating its oil-gas exploration potential. In this study, we processed and interpreted the gravity anomaly data obtained from the study area based on our understanding of its structural characteristics, and the conclusions drawn from the results are as follows. Under the influence of dextral shear stress of the central Africa shear zone, large-scale NW-oriented basement faults and small-scale NE-oriented caprock faults developed in the study area with the latter cutting off the former. The basement depth of the study area varies greatly and is characterized by "one uplift between two depressions". The very thick Mesozoic and Cenozoic cover layer was deposited in depressions. Controlled by the NW-tensional fault as well as the NE-fault developed along the structural weak zone, the study area is divided into four tectonic units: the eastern depression, the central uplift, the southern uplift and the western depression, showing the structural pattern of the "east-west zone and north-south block".

In order to effectively safeguard and improve the quality of the grain and oil products in China, to further implement the requirements of the grain supply-side reform, and to finish the regional “China Good Grain and Oil” project management work including product selection, as well as the quality and logistics traceability from field to dining table, this paper studies and analyzes the status quo, as well as the problems in the “China Good Grain and Oil” regional project management and business operation modes, suggesting to use information platform construction as a the supplementary mean for management work, so as to effectively improve the regional management in the “China Good Grain and Oil” project.

BackgroundCOVID-19 has presented a challenge for dental settings and dental schools: how to continue providing dental care and maintain education during the pandemic while remaining healthy. We highlight the necessity of infection containment control training for dental residents and rethink the tasks of safeguarding trainees' health and cultivating their abilities to deal with public health crises in the future. This paper may also serve as a health policy reference for policy makers.ObjectiveThe study aimed to compare the formats, frequency, contents, emphasis, and test scores of infection containment control training pre- and post-pandemic. Besides, after the COVID-19 outbreak, we assessed the increased anxiety level, communication difficulties, and confidence of dental residents impacted by the pandemic.MethodsA total of 251 dental residents in Stomatological Hospital of Chongqing Medical University were recruited to complete a questionnaire of their routine involvement in infection control training before and after the COVID-19 outbreak. A self-designed 10-point Likert scale was used to assess the increased anxiety level, communication difficulties, and confidence in facing with the future public health crisis impacted by the pandemic.ResultsAfter the outbreak, although more trainees chose online assessment than offline assessment, most of them (74.90%) still preferred in-person training rather than online training. Contents that trainees had been focusing on were affected by the COVID-19 outbreak. Thereafter, they were more inclined to learn crisis management. Over half of the participants (56.17%) participated in training more frequently after the outbreak. However, postgraduate students participated in training less frequently than others after the outbreak (p < 0.01). First-year trainees accounted for the majority in the population who emphasized considerably on infection control training and whose test scores had increased after the outbreak. In addition, the percentage of women scoring increasingly in post-pandemic assessment was significantly higher than that of men. In this study, the average increased anxiety level caused by COVID-19 was 5.51 ± 2.984, which was positively related to communication difficulties with patients caused by the pandemic. The trainees whose homes were located in Hubei Province showed higher increased anxiety levels (8.29 ± 2.93) impacted by the pandemic than the trainees from other provinces (p < 0.05). However, the former's confidence in coping with future public health crises was not significantly different from that of others (p > 0.05).ConclusionsOwing to the impact of COVID-19, the contents that the trainees focused on, frequency, emphasis, and test scores of infection containment control training were changed. Some recommendations have been provided for policy makers to attach importance to crisis-based training to cultivate dental residents in the post-pandemic era.

Background: Limited data exist regarding the efficacy and long-term safety of nucleos(t)ide analogue therapy throughout pregnancy for women with chronic hepatitis B and their children. Methods: This retrospective cohort study included 165 women in total: 91 women received telbivudine (LDT) and 74 women received tenofovir (TDF) throughout pregnancy. The virological response and safety in women were recorded, and the physical development and bone mineral density in children were evaluated up to 5 years of age. Results: The rate of virological breakthrough in women was 4.24% overall (7.70% in LDT group and 0% in TDF group; P < 0.05). No cases of renal injury or other obstetric adverse events occurred in either group of women. Among the children, only one child had a significantly low Z score for weight for age (

Abstract The prognosis of Artificial liver support system (ALSS) for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is hard to be expected, which results in multiple operations of ALSS and excessive consumption of plasma, increase in clinical cost. A total of 375 HBV-ACLF patients receiving ALSS treatment were randomly divided a train set and an independent test set. Logistic regression analysis was conducted and a decision tree was built based on 3-month survival as outcome. The ratio of total bilirubin before and after the first time of ALSS treatment was the most significant prognostic factor, we named it RPTB. Further, a decision tree based on the multivariate logistic regression model using CTP score and the RPTB was built, dividing patients into 3 main groups such as favorable prognosis group, moderate prognosis group and poor prognosis group. A clearly-presented and easily-understood decision tree was built with a good predictive value of prognosis in HBV-related ACLF patients after first-time ALSS treatment. It will help maximal the therapeutic value of ALSS treatment and may play an important role in organ allocation for liver transplantation in the future.

Wolbachia and Rickettsia are bacterial endosymbionts that can induce a number of reproductive abnormalities in their arthropod hosts. We screened and established the co-infection of Wolbachia and Rickettsia in Bemisia tabaci and compared the spatial and temporal distribution of Wolbachia and Rickettsia in eggs (3–120 h after spawning), nymphs, and adults of B. tabaci by qPCR quantification and fluorescent in situ hybridization (FISH). The results show that the titer of Wolbachia and Rickettsia in the 3–120 h old eggs showed a “w” patterned fluctuation, while the titers of Wolbachia and Rickettsia had a “descending–ascending descending–ascending” change process. The titers of Rickettsia and Wolbachia nymphal and the adult life stages of Asia II1 B. tabaci generally increased with the development of whiteflies. However, the location of Wolbachia and Rickettsia in the egg changed from egg stalk to egg base, and then from egg base to egg posterior, and finally back to the middle of the egg. These results will provide basic information on the quantity and localization of Wolbachia and Rickettsia within different life stages of B. tabaci. These findings help to understand the dynamics of the vertical transmission of symbiotic bacteria.

Grain and oil quality sampling is an important work in grain trading, storage and processing. To reserve the process sample and test the quality have important sense to guarantee fair trade and control grain quality in grain storage and processing. To resolve the problem in field grain quality sampling such as lack of regional representation, process fraud and difficulty in grassroots organization building, a field grain quality sampling management mode and relative techniques based on GIS and cloud platform was provided in this article. It not only standardized the sampling process, but also realized a real-time recording and monitoring of sampling process, ensured a fair and just sample testing process, reduced fraud in the process. The sampling and testing result can be easily handled in a visible and direct way. The management style of platform rental can solve the problem of construction fund and technicians shortages at the grassroots level.

Abstract Background The early detection of tumors upon initial diagnosis or during routine surveillance is important for improving survival outcomes. Here, we investigated the feasibility and clinical significance of circulating tumor DNA (ctDNA) detection for Extranodal NK/T-cell lymphoma, nasal type (ENTKL). Methods The plasma ctDNA assessment was based on blood specimens collected from 65 newly diagnosed patients with ENKTL in the hematology medical center of Xinqiao Hospital. Longitudinal samples collected under chemotherapy were also included. The gene mutation spectrum of ENKTL was analyzed via next generation sequencing. Results We found that the most frequently mutated genes were KMT2D (23.1%), APC (12.3%), ATM (10.8%), ASXL3 (9.2%), JAK3 (9.2%), SETD2 (9.2%), TP53 (9.2%) and NOTCH1 (7.7%). The mutation allele frequencies of ATM and JAK3 were significantly correlated with the disease stage, and mutated KMT2D, ASXL3 and JAK3 were positively correlated with the metabolic tumor burden of the patients. Compared with the tumor tissue, ctDNA profiling showed good concordance (93.75%). Serial ctDNA analysis showed that treatment with chemotherapy could decrease the number and mutation allele frequencies of the genes. Compared with PET/CT, ctDNA has more advantages in tracking residual disease in patients. In addition, patients with mutated KMT2D had higher expression compared with those with wild type, and mutated KMT2D predicted poor prognosis. Conclusion Our results unveil the mutation spectrum of ENKTL patients’ plasma, which can be used to monitor the disease status of the patients exactly, and KMT2D is the most frequently mutated gene with prognosis prediction value. The application of ctDNA sequencing can provide precision treatment strategies for patients. Trial registration This study is registered with chictr.org ( ChiCTR1800014813 , registered 7 February, 2018-Retrospectively registered).

Abstract Chimeric antigen receptor T (CAR-T) cell therapy is regarded as an effective solution for relapsed or refractory tumors, particularly for hematological malignancies. Although the initially approved anti-CD19 CAR-T therapy has produced impressive outcomes, setbacks such as high relapse rates and resistance were experienced, driving the need to discover engineered CAR-T cells that are more effective for therapeutic use. Innovations in the structure and manufacturing of CAR-T cells have resulted in significant improvements in efficacy and persistence, particularly with the development of fourth-generation CAR-T cells. Paired with an immune modifier, the use of fourth-generation and next-generation CAR-T cells will not be limited because of cytotoxic effects and will be an efficient tool for overcoming the tumor microenvironment. In this review, we summarize the recent transformations in the ectodomain, transmembrane domain, and endodomain of the CAR structure, which, together with innovative manufacturing technology and improved cell sources, improve the prospects for the future development of CAR-T cell therapy.

According to previous reports,10–16% of patients with clinically advanced cholangiocarcinoma develop FGFR2 fusions or rearrangements. Treatment with FGFR2-specific inhibitors (tyrosine kinase inhibitors, TKIs) has proven effective for patients with cholangiocarcinoma. In this study, we report a case of advanced cholangiocarcinoma, in which the patient was unable to tolerate the adverse effects of standard first-line chemotherapy. Genetic testing suggested the presence of a novel variant resulting from FDFT1/FGFR2 rearrangement. Owing to poor accessibility and high price, only a limited number of patients with advanced cholangiocarcinoma have access to TKIs and precision targeted therapy in China. Anlotinib is a novel small-molecule multi-target TKI developed independently in China. It has a broad target spectrum, including FGFR, and can effectively inhibit tumor angiogenesis and tumor cell proliferation, thereby achieving an anti-tumor effect. Here, the patient was prescribed anlotinib. After treatment, the tumor size continued to shrink, and no significant adverse effects were reported. The finding suggested that anlotinib may be effective in patients with FDFT1/FGFR2 rearrangement and could serve as a novel treatment option for affected patients in future.

Endosymbionts play an essential role in the biology, physiology and immunity of insects. Many insects, including the whitefly Bemisia tabaci, are infected with the facultative endosymbiont Rickettsia. However, the mutualism between Rickettsia and its whitefly host remains unclear. This study investigated the biological and physiological benefits of Rickettsia infection to B. tabaci. Results revealed that infection of Rickettsia increased the fertility, the survival rate from nymph to adult and the number of female whiteflies. In addition, this facilitation caused a significant reduction in nymphal developmental duration but did not affect percentage rate of egg hatching. Rickettsia infected B. tabaci had significantly higher glycogen, soluble sugar and trehalose contents than Rickettsia negative B. tabaci individuals. Rickettsia also improved the immunity of its whitefly hosts. Rickettsia infested B. tabaci had lower mortality rates and higher semi-lethal concentrations (LC50) when exposed to the fungus Akanthomyces attenuatus and the insecticides imidacloprid and spirotetramat. The percentage of parasitism by Encarsia formosa was also reduced by Rickettsia infection. Overall, Rickettsia infection benefits B. tabaci by improving the nutritional composition of its host, and also protects B. tabaci by enhancing its resistance towards insecticides (imidacloprid and spirotetramat), entomopathogenic fungi (A. attenuatus) and its main parasitoid (E. formosa); all of which could significantly impact on current management strategies.