IL-2-free tumor-infiltrating lymphocyte therapy with PD-1 blockade demonstrates potent efficacy in advanced gynecologic cancer.

BACKGROUND: Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer. METHODS: Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, duration of response, and T cell persistence. RESULTS: In matched patient-derived xenografts (PDX) models, homologous TILs efficiently reduced tumor size (p < 0.0001) and underwent IL-2 absence in vivo. In the clinical section, all enrolled patients received TIL infusion using a modified TIL therapy regimen successfully with a manageable safety profile. Five (36%, 95% CI 16.3-61.2) out of 14 evaluable patients experienced objective responses, and three complete responses were ongoing at 19.5, 15.4, and 5.2 months, respectively. Responders had longer overall survival (OS) than non-responders (p = 0.036). Infused TILs showed continuous proliferation and long-term persistence in all patients and showed greater proliferation in responders which was indicated by the Morisita overlap index (MOI) of TCR clonotypes between infused TILs and peripheral T cells on day 14 (p = 0.004) and day 30 (p = 0.004). Higher alteration of the CD8+/CD4+ ratio on day 14 indicated a longer OS (p = 0.010). CONCLUSIONS: Our modified TIL therapy regimen demonstrated manageable safety, and TILs could survive and proliferate without IL-2 intravenous administration, showing potent efficacy in patients with advanced gynecologic cancer. TRIAL REGISTRATION: NCT04766320, Jan 04, 2021.

Preparation of Medical 228Th-224Ra Radionuclide Generator Based on SiO2@TiO2 Microspheres.

224Ra (T1/2 = 3.63 d), an α-emitting radionuclide, holds significant promise in cancer endoradiotherapy. Current 224Ra-related therapy is still scarce because of the lack of reliable radionuclide supply. The 228Th-224Ra radionuclide generator can undoubtedly introduce continuous and sustainable availability of 224Ra for advanced nuclear medicine. However, conventional metal oxides for such radionuclide generators manifest suboptimal adsorption capacities for the parent nuclide, primarily attributable to their limited surface area. In this work, core-shell SiO2@TiO2 microspheres were proposed to develop as column materials for the construction of a 228Th-224Ra generator. SiO2@TiO2 microspheres were well prepared and systematically characterized, which has also been demonstrated to have good adsorption capacity to 228Th and very weak binding affinity toward 224Ra via simulated chemical separation. Upon introducing 228Th-containing solution onto the SiO2@TiO2 functional column, a 228Th-224Ra generator with excellent retention of the parent radionuclide and ideal elution efficiency of daughter radionuclide was obtained. The prepared 228Th-224Ra generator can produce 224Ra with high purity and medical usability in good elution efficiency (98.72%) even over five cycles. To the best of our knowledge, this is the first time that the core-shell mesoporous materials have been applied in a radionuclide generator, which can offer valuable insights for materials chemistry, radiochemical separation, and biological medicine.

Nematicidal glycosylated resorcylic acid lactones from the fungus Pochonia chlamydosporia PC-170 and their key biosynthetic genes.

Chemical study of the nematicidal biocontrol fungus Pochonia chlamydosporia PC-170 led to discovery of six resorcylic acid lactones (RALs), including three nematicidal glycosylated RALs, monocillin VI glycoside (1), colletogloeolactone A (2) and monocillin II glycoside (3), and three antibacterial non-glycosylated RALs, monocillin VI (4), monocillin IV (5) and monocillin II (6). The planar structure of the new compound monocillin VI glycoside (1) was elucidated using HRESIMS and NMR data, and its monosaccharide configuration was further determined through sugar hydrolysis experiment and GC-MS analysis method. Furthermore, their two biosynthetic-related PKS genes, pchE and pchI, were identified through the gene knockout experiment. The glycosylated RALs 1-3 exhibited nematicidal activity against Meloidogyne incognita, with LC50 values of 94, 152 and 64 µg/mL, respectively, and thus had great potential in the development of new nematicidal natural products to control M. incognita in the future.

The secreted micropeptide C4orf48 enhances renal fibrosis via an RNA-binding mechanism.

Renal interstitial fibrosis is an important mechanism in the progression of chronic kidney disease (CKD) to end-stage kidney disease. However, we lack specific treatments to slow or halt renal fibrosis. Ribosome profiling identified upregulation of a secreted micropeptide, C4orf48 (Cf48), in mouse diabetic nephropathy. Cf48 RNA and protein levels were upregulated in tubular epithelial cells in human and experimental CKD. Serum Cf48 levels were increased in human CKD and correlated with loss of kidney function, increasing CKD stage, and the degree of active interstitial fibrosis. Cf48 overexpression in mice accelerated renal fibrosis, while Cf48 gene deletion or knockdown by antisense oligonucleotides significantly reduced renal fibrosis in CKD models. In vitro, recombinant Cf48 (rCf48) enhanced TGF-ß1-induced fibrotic responses in renal fibroblasts and epithelial cells independently of Smad3 phosphorylation. Cellular uptake of Cf48 and its profibrotic response in fibroblasts operated via the transferrin receptor. RNA immunoprecipitation-sequencing identified Cf48 binding to mRNA of genes involved in the fibrotic response, including Serpine1, Acta2, Ccn2, and Col4a1. rCf48 binds to the 3'UTR of Serpine1 and increases mRNA half-life. We identify the secreted Cf48 micropeptide as a potential enhancer of renal fibrosis that operates as an RNA-binding peptide to promote the production of extracellular matrix.

The efficacy and safety of electroacupuncture for diabetic peripheral neuropathy: A protocol for a systematic review and meta-analysis.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes mellitus, which is the most common neuropathy worldwide. Owing to the inadequacies of existing treatment methods, managing DPN remains a significant challenge. Studies suggest that electroacupuncture (EA) could potentially serve as a beneficial alternative treatment for this condition. Nevertheless, there is still inadequate proof of its therapeutic effectiveness and safety. As a result, the goal of this protocol is to methodically compile the data pertaining to the effectiveness and security of EA in the management of DPN. METHODS: To find appropriate randomized controlled trials (RCTs), nine reliable databases in the English and Chinese languages will be examined. RevMan5.3 will be used to combine the retrieved data and perform meta-analyses. The methodological quality of the included RCTs will be evaluated using the Cochrane Risk of Bias Assessment 2.0 tool. The Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) system will be utilized to evaluate the degree of strength and certainty of the evidence. We will also perform publication bias, sensitivity and subgroup analyses. DISCUSSION: This protocol describes the intended scope and approach for a forthcoming systematic review and meta-analysis that will inform therapeutic decision-making by offering current information on the efficacy and safety of EA in the treatment of DPN. The results of the study will help standardize strategies for EA in the treatment of DPN.

A novel LINC02321 promotes cell proliferation and decreases cisplatin sensitivity in bladder cancer by regulating RUVBL2.

Bladder cancer (BC) has a high incidence and is prone to recurrence. In most instances, the low 5-year survival rate of advanced BC patients results from postoperative recurrence and drug resistance. Long noncoding RNAs (lncRNAs) can participate in numerous biological functions by regulating the expression of genes to affect tumorigenesis. Our previous work had demonstrated that a novel lncRNA, LINC02321, was associated with BC prognosis. In this study, A high expression of LINC02321 was found in BC tissues, which was associated with poor prognosis in patients. LINC02321 promoted both proliferation and G1-G0 progression in BC cells, while also inhibited sensitivity to cisplatin. Mechanistically, LINC02321 can bind to RUVBL2 and regulate the expression levels of RUVBL2 protein by affecting its half-life. RUVBL2 is involved in the DNA damage response. The potential of DNA damage repair pathways to exert chemosensitization has been demonstrated in vivo. The rescue experiment demonstrated that RUVBL2 overexpression can markedly abolish the decreased cell proliferation and the increased sensitivity of BC cells to cisplatin caused by LINC02321 knockdown. The results indicate that LINC02321 functions as an oncogene in BC, and may serve as a novel potential target for controlling BC progression and addressing cisplatin resistance in BC therapy.

An electrochemical immunosensor based on hybrid self-assembled monolayers for rapid detection of Bombyx mori nucleopolyhedrovirus.

Bombyx mori nucleopolyhedrovirus (BmNPV) is highly contagious and poses a serious threat to sericulture production. Because there are currently no effective treatments for BmNPV, a rapid and simple detection method is urgently needed. This paper describes an electrochemical immunosensor for the detection of BmNPV. The immunosensor was fabricated by covalently immobilizing anti-BmNPV, a biorecognition element, onto the surface of the working gold electrode via 11-mercaptoundecanoic acid (MUA)/ß-mercaptoethanol (ME) hybrid self-assembled monolayers. Electrochemical impedance spectroscopy (EIS) and atomic force microscopy (AFM) were used to characterize the electrochemical performance and morphology of the immunosensor, respectively. Under optimum conditions, the developed immunosensor exhibited a linear response to BmNPV polyhedrin in the range of 1 × 102-1 × 108 fg/mL, with a low detection limit of 14.54 fg/mL. The immunosensor also exhibited remarkable repeatability, reproducibility, specificity, accuracy, and regeneration. Normal silkworm blood was mixed with BmNPV polyhedrin and analyzed quantitatively using this sensor, and the recovery was 92.31 %-100.61 %. Additionally, the sensor was used to analyze silkworm blood samples at different time points after BmNPV infection, and an obvious antigen signal was detected at 12 h post infection. Although this result agreed with that provided by the conventional polymerase chain reaction (PCR) method, the electroanalysis method established in this study was simpler, shorter in detection period, and lower in material cost. Furthermore, this innovative electrochemical immunosensor, developed for the ultra-sensitive and rapid detection of BmNPV, can be used for the early detection of virus-infected silkworms.

Transcriptomic insights into the lipotoxicity of high-fat high-fructose diet in rat and mouse.

Along with the increasing prevalence of obesity worldwide, the deleterious effects of high-calorie diet are gradually recognized through more and more epidemiological studies. However, the concealed and chronic causality whitewashes its unhealthy character. Given an ingenious mechanism orchestrates the metabolic adaptation to high-fat high-fructose (HFF) diet and connive its lipotoxicity, in this study, an experimental rat/mouse model of obesity was induced and a comparative transcriptomic analysis was performed to probe the mystery. Our results demonstrated that HFF diet consumption altered the transcriptomic pattern as well as different high-calorie diet fed rat/mouse manifested distinct hepatic transcriptome. Validation with RT-qPCR and Western blotting confirmed that SREBP1-FASN involved in de novo lipogenesis partly mediated metabolic self-adaption. Moreover, hepatic ACSL1-CPT1A-CPT2 pathway involved in fatty acids ß-oxidation, played a key role in the metabolic adaption to HFF. Collectively, our findings enrich the knowledge of the chronic adaptation mechanisms and also shed light on future investigations. Meanwhile, our results also suggest that efforts to restore the fatty acids metabolic fate could be a promising avenue to fight against obesity and associated steatosis and insulin resistance challenged by HFF diet.

Proteomics-Based Identification of Potential Therapeutic Targets of Artesunate in a Lupus Nephritis MRL/lpr Mouse Model.

This study aimed to identify potential therapeutic targets of artesunate in an MRL/lpr lupus nephritis mouse model by quantitative proteomics. We detected serum autoimmune markers and proteinuria in 40 female mice that were divided into 4 groups (n = 10): normal C57BL/6 control group; untreated MRL/lpr lupus; 9 mg/kg/day prednisone positive control MRL/lpr lupus; and 15 mg/kg/day artesunate-treated MRL/lpr lupus groups. Renal pathology in the untreated MRL/lpr lupus and artesunate groups was examined by Periodic acid-Schiff (PAS) staining. Artesunate treatment in lupus mice decreased serum autoantibody levels and proteinuria while alleviating lupus nephritis pathology. Through tandem mass tag-tandem mass spectrometry (TMT-MS/MS) analyses, differentially expressed proteins were identified in the artesunate group, and subsequent functional prediction suggested associations with antigen presentation, apoptosis, and immune regulation. Data are available via ProteomeXchange with the identifier PXD046815. Parallel reaction monitoring (PRM) analysis of the top 19 selected proteins confirmed the TMT-MS/MS results. Immunohistochemistry, immunofluorescence, and Western blotting of an enriched protein from PRM analysis, cathepsin S, linked to antigen presentation, highlighted its upregulation in the untreated MRL/lpr lupus group and downregulation following artesunate treatment. This study suggests that artesunate holds potential as a therapeutic agent for lupus nephritis, with cathepsin S identified as a potential target.

METTL3 confers protection against mitochondrial dysfunction and cognitive impairment in an Alzheimer disease mouse model by upregulating Mfn2 via N6-methyladenosine modification.

Mitofusin 2 (MFN2) has been found to be downregulated in patients with Alzheimer disease (AD) but little is known about its roles in the pathogenesis of AD. We explored the mechanism of N6-methyladenosine (m6A) methylation of Mfn2 in hippocampal mitochondrial dysfunction in an AD mouse model. APP/PS1 transgenic mice underwent stereotaxic injection of adeno-associated viruses and their behaviors were assessed. METTL3 and MFN2 expressions were measured by qRT-PCR and Western blot, accompanied by assessment of mitochondrial morphology, ATP, mitochondrial membrane potential, and amyloid-ß content. Binding between METTL3 and MFN2, the total amount of m6A, and the m6A modification of Mfn2 were also determined. METTL3 and MFN2 were downregulated in hippocampal tissues of the AD model mice; METTL3 enhanced MFN2 expression via m6A modification. Overexpression of METTL3 or MFN2 ameliorated mitochondrial dysfunction indicated by fewer damaged mitochondria, increased ATP and JC-1 levels, and reduced Aß content; improved cognitive impairment in the mice was indicated by the novel object discrimination index and Morris water maze tests. Effects of METTL3 overexpression were abrogated by further knockdown of MFN2. Thus, METTL3 ameliorated mitochondrial dysfunction and cognitive impairment in the AD model mice by increasing MFN2 expression via m6A modification.

Single-cell profiling reveals kidney CD163+ dendritic cell participation in human lupus nephritis.

OBJECTIVES: The current work aimed to provide a comprehensive single-cell landscape of lupus nephritis (LN) kidneys, including immune and non-immune cells, identify disease-associated cell populations and unravel their participation within the kidney microenvironment. METHODS: Single-cell RNA and T cell receptor sequencing were performed on renal biopsy tissues from 40 patients with LN and 6 healthy donors as controls. Matched peripheral blood samples from seven LN patients were also sequenced. Multiplex immunohistochemical analysis was performed on an independent cohort of 60 patients and validated using flow cytometric characterisation of human kidney tissues and in vitro assays. RESULTS: We uncovered a notable enrichment of CD163+ dendritic cells (DC3s) in LN kidneys, which exhibited a positive correlation with the severity of LN. In contrast to their counterparts in blood, DC3s in LN kidney displayed activated and highly proinflammatory phenotype. DC3s showed strong interactions with CD4+ T cells, contributing to intrarenal T cell clonal expansion, activation of CD4+ effector T cell and polarisation towards Th1/Th17. Injured proximal tubular epithelial cells (iPTECs) may orchestrate DC3 activation, adhesion and recruitment within the LN kidneys. In cultures, blood DC3s treated with iPTECs acquired distinct capabilities to polarise Th1/Th17 cells. Remarkably, the enumeration of kidney DC3s might be a potential biomarker for induction treatment response in LN patients. CONCLUSION: The intricate interplay involving DC3s, T cells and tubular epithelial cells within kidneys may substantially contribute to LN pathogenesis. The enumeration of renal DC3 holds potential as a valuable stratification feature for guiding LN patient treatment decisions in clinical practice.

A Natural Small Molecule Mitigates Kidney Fibrosis by Targeting Cdc42-mediated GSK-3ß/ß-catenin Signaling.

Kidney fibrosis is a common fate of chronic kidney diseases (CKDs), eventually leading to renal dysfunction. Yet, no effective treatment for this pathological process has been achieved. During the bioassay-guided chemical investigation of the medicinal plant Wikstroemia chamaedaphne, a daphne diterpenoid, daphnepedunin A (DA), is characterized as a promising anti-renal fibrotic lead. DA shows significant anti-kidney fibrosis effects in cultured renal fibroblasts and unilateral ureteral obstructed mice, being more potent than the clinical trial drug pirfenidone. Leveraging the thermal proteome profiling strategy, cell division cycle 42 (Cdc42) is identified as the direct target of DA. Mechanistically, DA targets to reduce Cdc42 activity and down-regulates its downstream phospho-protein kinase Cζ(p-PKCζ)/phospho-glycogen synthase kinase-3ß (p-GSK-3ß), thereby promoting ß-catenin Ser33/37/Thr41 phosphorylation and ubiquitin-dependent proteolysis to block classical pro-fibrotic ß-catenin signaling. These findings suggest that Cdc42 is a promising therapeutic target for kidney fibrosis, and highlight DA as a potent Cdc42 inhibitor for combating CKDs.

Using an artificial intelligence model to detect and localize visible clinically significant prostate cancer in prostate magnetic resonance imaging: a multicenter external validation study.

Background: An increasing number of patients with suspected clinically significant prostate cancer (csPCa) are undergoing prostate multiparametric magnetic resonance imaging (mpMRI). The role of artificial intelligence (AI) algorithms in interpreting prostate mpMRI needs to be tested with multicenter external data. This study aimed to investigate the diagnostic efficacy of an AI model in detecting and localizing visible csPCa on mpMRI a multicenter external data set. Methods: The data of 2,105 patients suspected of having prostate cancer from four hospitals were retrospectively collected to develop an AI model to detect and localize suspicious csPCa. The lesions were annotated based on pathology records by two radiologists. Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) values were used as the input for the three-dimensional U-Net framework. Subsequently, the model was validated using an external data set comprising the data of 557 patients from three hospitals. Sensitivity, specificity, and accuracy were employed to evaluate the diagnostic efficacy of the model. Results: At the lesion level, the model had a sensitivity of 0.654. At the overall sextant level, the model had a sensitivity, specificity, and accuracy of 0.846, 0.884, and 0.874, respectively. At the patient level, the model had a sensitivity, specificity, and accuracy of 0.943, 0.776, and 0.849, respectively. The AI-predicted accuracy for the csPCa patients (231/245, 0.943) was significantly higher than that for the non-csPCa patients (242/312, 0.776) (P<0.001). The lesion number and tumor volume were greater in the correctly diagnosed patients than the incorrectly diagnosed patients (both P<0.001). Among the positive patients, those with lower average ADC values had a higher rate of correct diagnosis than those with higher average ADC values (P=0.01). Conclusions: The AI model exhibited acceptable accuracy in detecting and localizing visible csPCa at the patient and sextant levels. However, further improvements need to be made to enhance the sensitivity of the model at the lesion level.

Abalone peptide increases stress resilience and cost-free longevity via SKN-1-governed transcriptional metabolic reprogramming in C. elegans.

A major goal of healthy aging is to prevent declining resilience and increasing frailty, which are associated with many chronic diseases and deterioration of stress response. Here, we propose a loss-or-gain survival model, represented by the ratio of cumulative stress span to life span, to quantify stress resilience at organismal level. As a proof of concept, this is demonstrated by reduced survival resilience in Caenorhabditis elegans exposed to exogenous oxidative stress induced by paraquat or with endogenous proteotoxic stress caused by polyglutamine or amyloid-ß aggregation. Based on this, we reveal that a hidden peptide ("cryptide")-AbaPep#07 (SETYELRK)-derived from abalone hemocyanin not only enhances survival resilience against paraquat-induced oxidative stress but also rescues proteotoxicity-mediated behavioral deficits in C. elegans, indicating its capacity against stress and neurodegeneration. Interestingly, AbaPep#07 is also found to increase cost-free longevity and age-related physical fitness in nematodes. We then demonstrate that AbaPep#07 can promote nuclear localization of SKN-1/Nrf, but not DAF-16/FOXO, transcription factor. In contrast to its effects in wild-type nematodes, AbaPep#07 cannot increase oxidative stress survival and physical motility in loss-of-function skn-1 mutant, suggesting an SKN-1/Nrf-dependent fashion of these effects. Further investigation reveals that AbaPep#07 can induce transcriptional activation of immune defense, lipid metabolism, and metabolic detoxification pathways, including many SKN-1/Nrf target genes. Together, our findings demonstrate that AbaPep#07 is able to boost stress resilience and reduce behavioral frailty via SKN-1/Nrf-governed transcriptional reprogramming, and provide an insight into the health-promoting potential of antioxidant cryptides as geroprotectors in aging and associated conditions.

Remarkable N2-selectivity enhancement of NH3-SCR over HPMo modified MnCo-BTC@SiO2 catalyst.

In this work, the phosphomolybdate (HPMo) modification strategy was applied to improve the N2 selectivity of MnCo-BTC@SiO2 catalyst for the selective catalytic reduction of NOx, and further, the mechanism of HPMo modification on enhanced catalytic performance was explored. Among MnCo-BTC@SiO2-x catalysts with different HPMo concentrations, MnCo-BTC@SiO2-0.75 catalyst exhibited not only the highest NH3-SCR performance (∼95% at 200-300°C) but also the best N2 selectivity (exceed 80% at 100-300°C) due to the appropriate redox capacity, greater surface acidity. X-ray photoelectron spectrometer (XPS) and temperature programmed reduction of H2 (H2-TPR) results showed that the modification with HPMo reduced the oxidation-reduction performance of the catalyst due to electron transfer from Mo5+ to Mn4+/Mn3+ and prevent the excessive oxidation of ammonia adsorption species. NH3 temperature-programmed desorption of (NH3-TPD) results showed that the modification with HPMo could significantly improve the surface acidity and NH3 adsorption, which enhance the catalytic activity and N2 selectivity. In-situ diffused reflectance infrared Fourier transform spectroscopy (in-situ DRIFTS) revealed that modification with HPMo increased significantly the amount of adsorbed NH3 species on the Bronsted acid site and CB/CL, it suppressed the production of N2O by inhibiting the production of NH species, the deep dehydrogenation of ammonia adsorption species. This study provided a simple design strategy for the catalyst to improve the low-temperature catalytic performance and N2 selectivity.

Use of metagenomic next-generation sequencing for diagnosis of peritonitis in end-stage liver disease.

Background: Conventional methods are low in positive rates and time-consuming for ascites pathogen detection in patients with end-stage liver disease (ESLD). With many advantages, metagenomic next-generation sequencing (mNGS) may be a good alternative method. However, the related studies are still lacking. Methods: Ascites from 50 ESLD patients were sampled for pathogen detection using mNGS and conventional methods (culture and polymorphonuclear neutrophils detection) in this prospective observational study. Results: Forty-two samples were detected positive using mNGS. 29 strains of bacteria, 11 strains of fungi, and 9 strains of viruses were detected. 46% of patients were detected to be co-infected with 2 or more pathogens by mNGS. Moreover, mNGS showed similar and high positive rates in ESLD patients with different clinical characteristics. Compared to conventional methods, mNGS had higher positivity rates (84% vs. 20%, P<0.001), sensitivity (45.2% vs. 23.8%, P=0.039), broader pathogen spectrum, shorter detection time (24 hours vs. 3-7 days), but lower specificity (25% vs 100%, P = 0.010). Furthermore, compared to conventional methods, mNGS showed similar consistence with final diagnosis (42% vs. 36%, P=0.539). Conclusions: mNGS may be a good supplement for conventional methods and helpful to early etiological diagnosis of peritonitis, and thus improve ESLD patients' survival.

Comparative Genomics Reveals Three Genetic Groups of the Whitefly Obligate Endosymbiont Candidatus Portiera aleyrodidarum.

Maternally inherited obligate endosymbionts codiverge with their invertebrate hosts and reflect their host's evolutionary history. Whiteflies (Hemiptera: Aleyrodidae) harbor one obligate endosymbiont, Candidatus Portiera aleyrodidarum (hereafter Portiera). Portiera was anciently acquired by whitefly and has been coevolving with its host ever since. Uncovering the divergence of endosymbionts provides a fundamental basis for inspecting the coevolutionary processes between the bacteria and their hosts. To illustrate the divergence of Portiera lineages across different whitefly species, we sequenced the Portiera genome from Aleyrodes shizuokensis and conducted a comparative analysis on the basic features and gene evolution with bacterial genomes from five whitefly genera, namely Aleurodicus, Aleyrodes, Bemisia, Pealius, and Trialeurodes. The results indicated that Portiera from Bemisia possessed significantly larger genomes, fewer coding sequences (CDSs), and a lower coding density. Their gene arrangement differed notably from those of other genera. The phylogeny of the nine Portiera lineages resembled that of their hosts. Moreover, the lineages were classified into three distinct genetic groups based on the genetic distance, one from Aleurodicus (Aleurodicinae), one from Bemisia (Aleyrodinae), and another from Aleyrodes, Pealius, and Trialeurrodes (Aleyrodinae). Synonymous and nonsynonymous rate analyses, parity rule 2 plot analyses, neutrality plot analyses, and effective number of codons analyses supported the distinction of the three genetic groups. Our results indicated that Portiera from distant hosts exhibit distinct genomic contents, implying codivergence between hosts and their endosymbionts. This work will enhance our understanding of coevolution between hosts and their endosymbionts.

Shock-Induced Microstructural Evolution, Phase Transformation, Sintering of Al-Ni Dissimilar Nanoparticles: A Molecular Dynamics Study.

Molecular dynamic simulations have been performed to explore contact behavior, microstructure evolution and sintering mechanism of Al-Ni dissimilar nanoparticles under high-velocity impact. We confirmed that the simulated contact stress, contact radius, and contact force under low-velocity impact are in good agreement with the predicted results of the Hertz model. However, with increasing the impact velocity, the simulated results gradually deviate from the predicted results of the Hertz model due to the elastic-plastic transition and atomic discrete structure. The normalized contact radius versus strain exhibits a weak dependence on nanosphere diameter. Below a critical velocity, there are very few HCP atoms in the nanospheres after thermal equilibrium. There are two different sintering mechanisms: under low-velocity impact, the sintering process relies mainly on the dislocation slip of Al nanospheres, while the dislocation slip of Ni nanospheres and the atomic diffusion of Al nanospheres predominate under high-velocity impact.

Nomogram based on clinical and preoperative CT features for predicting the early recurrence of combined hepatocellular-cholangiocarcinoma: a multicenter study.

PURPOSE: To establish and validate a multiparameter prediction model for early recurrence after radical resection in patients diagnosed with combined hepatocellular-cholangiocarcinoma (cHCC-CC). MATERIALS AND METHODS: This study reviewed the clinical characteristics and preoperative CT images of 143 cHCC-CC patients who underwent radical resection from three institutions. A total of 110 patients from institution 1 were randomly divided into training set (n = 78) and testing set (n = 32) in the ratio of 7-3. Univariate and multivariate logistic regression analysis were used to construct a nomogram prediction model in the training set, which was internally and externally validated in the testing set and the validation set (n = 33) from institutions 2 and 3. The area under the curve (AUC) of receiver operating characteristics (ROC), decision curve analysis (DCA), and calibration analysis were used to evaluate the model's performance. RESULTS: The combined model demonstrated superior predictive performance compared to the clinical model, the CT model, the pathological model and the clinic-CT model in predicting the early postoperative recurrence. The nomogram based on the combined model included AST, ALP, tumor size, tumor margin, arterial phase peritumoral enhancement, and MVI (Microvascular invasion). The model had AUCs of 0.89 (95% CI 0.81-0.96), 0.85 (95% CI 0.70-0.99), and 0.86 (95% CI 0.72-1.00) in the training, testing, and validation sets, respectively, indicating high predictive power. DCA showed that the combined model had good clinical value and correction effect. CONCLUSION: A nomogram incorporating clinical characteristics and preoperative CT features can be utilized to effectively predict the early postoperative recurrence in patients with cHCC-CC.