Development and validation of a preoperative radiomics-based nomogram to identify patients who can benefit from splenic hilar lymphadenectomy: a pooled analysis of three prospective trials.

BACKGROUND: The authors aimed to use preoperative computed tomography images to develop a radiomic nomogram to select patients who would benefit from spleen-preserving splenic hilar (No.10) lymphadenectomy (SPSHL). METHODS: A pooled analysis of three distinct prospective studies was performed. The splenic hilar lymph node (SHLN) ratio (sLNR) was established as the quotient of the number of metastatic SHLN to the total number of SHLN. Radiomic features reflecting the phenotypes of the primary tumor (RS1) and SHLN region (RS2) were extracted and used as predictive factors for sLNR. RESULTS: This study included 733 patients: 301 in the D2 group and 432 in the D2+No.10 group. The optimal sLNR cutoff value was set at 0.4, and the D2+No.10 group was divided into three groups: sLNR=0, sLNR ≤0.4, and sLNR >0.4. Patients in the D2+No. 10 group were randomly divided into the training ( n =302) and validation ( n =130) cohorts. The AUCs value of the nomogram, including RS1 and RS2, were 0.952 in the training cohort and 0.888 in the validation cohort. The entire cohort was divided into three groups based on the nomogram scores: low, moderate, and high SHLN metastasis burden groups (LMB, MMB, and HMB, respectively). A similar 5-year OS rate was found between the D2 and D2+No. 10 groups in the LMB and HMB groups. In the MMB group, the 5-year OS of the D2+No. 10 group (73.4%) was significantly higher than that of the D2 group (37.6%) ( P <0.001). CONCLUSIONS: The nomogram showed good predictive ability for distinguishing patients with various SHLN metastasis burdens. It can accurately identify patients who would benefit from SPSHL.

Structural and spectroscopic insights into fucoxanthin chlorophyll a/c-binding proteins of diatoms in diverse oligomeric states.

Diatoms, a group of prevalent marine algae, significantly contribute to global primary productivity. Their substantial biomass is linked to enhanced absorption of blue-green light underwater, facilitated by fucoxanthin chlorophyll a/c-binding proteins (FCPs), exhibiting oligomeric diversity across diatom species. Utilizing mild CN-PAGE analysis on solubilized thylakoid membranes, we displayed monomeric, dimeric, trimeric, tetrameric and pentameric FCPs in diatoms. Mass spectrometry analysis revealed each oligomeric FCP has specific protein compositions, constituting a large Lhcf family of FCP antennas. In addition, we resolved the structures of Thalassiosira pseudonana FCP (Tp-FCP) homotrimer and Chaetoceros gracilis FCP (Cg-FCP) pentamer by cryo-electron microscopy at 2.73 Å and 2.65 Å resolutions, respectively. The distinct pigment composition and organization in various oligomeric FCPs change their blue-green light-harvesting, excitation energy transfer pathways. In comparison to dimeric and trimeric FCPs, Cg-FCP tetramer and Cg-FCP pentamer exhibit stronger absorption by Chls c, red-shifted and broader Chl a fluorescence emission, as well as more robust circular dichroism signals originating from Chl a-carotenoid dimers. These spectroscopic characteristics indicate that Chl a molecules in Cg-FCP tetramer and Cg-FCP pentamer are more heterogeneous than in both dimers and Tp-FCP trimer. The structural and spectroscopic insights provided by this study contribute to a better understanding of the mechanisms that empower diatoms to adapt to fluctuating light environments.

Knockdown of circ_0076305 decreases the paclitaxel resistance of non-small cell lung cancer cells by regulating TMPRSS4 via miR-936.

Background: Paclitaxel (PTX) is a commonly used as a chemotherapeutic drug for non-small cell lung cancer (NSCLC). Exploring the underlying mechanism of PTX resistance is of great significance for NSCLC treatment. Methods: The expression levels of RNA and protein were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The targeted relationship was confirmed by dual-luciferase reporter assay and RNA-pull down assay. The PTX resistance and cell proliferation were assessed by cell counting kit-8 (CCK-8) assay and 5-Ethynyl-2'-deoxyuridine (EDU) assay, respectively. Cell migration and invasion were analyzed by transwell assays. Cell apoptosis was analyzed by flow cytometry, and cell glycolysis was analyzed using the commercial kits. The role of circular RNA_0076305 (circ_0076305) in regulating the PTX sensitivity in vivo was explored in xenograft tumor model. Results: Circ_0076305 was up-regulated in PTX-resistant NSCLC tissues and cells. Mechanically, circ_0076305 bound to microRNA-936 (miR-936), and miR-936 targeted transmembrane serine protease 4 (TMPRSS4). Circ_0076305 could up-regulate TMPRSS4 expression by sponging miR-936 in NSCLC cells. miR-936 knockdown or TMPRSS4 overexpression reversed the anti-tumor effects of circ_0076305 knockdown in NSCLC cells with PTX treatment. Circ_0076305 silencing increased the PTX sensitivity of xenograft tumors in vivo. Conclusion: Circ_0076305 silencing promoted PTX sensitivity by targeting miR-936/TMPRSS4 axis in NSCLC cells.

A firm-push-to-open and light-push-to-lock strategy for a general chemical platform to develop activatable dual-modality NIR-II probes.

Activatable near-infrared (NIR) imaging in the NIR-II range is crucial for deep tissue bioanalyte tracking. However, designing such probes remains challenging due to the limited availability of general chemical strategies. Here, we introduced a foundational platform for activatable probes, using analyte-triggered smart modulation of the π-conjugation system of a NIR-II-emitting rhodamine hybrid. By tuning the nucleophilicity of the ortho-carboxy moiety, we achieved an electronic effect termed "firm-push-to-open and light-push-to-lock," which enables complete spirocyclization of the probe before sensing and allows for efficient zwitterion formation when the light-pushing aniline carbamate trigger is transformed into a firm-pushing aniline. This platform produces dual-modality NIR-II imaging probes with ~50-fold fluorogenic and activatable photoacoustic signals in live mice, surpassing reported probes with generally below 10-fold activatable signals. Demonstrating generality, we successfully designed probes for hydrogen peroxide (H2O2) and hydrogen sulfide (H2S). We envision a widespread adoption of the chemical platform for designing activatable NIR-II probes across diverse applications.

Robotic gastrectomy was reliable option for overweight patients with gastric cancer: a propensity score matching study.

BACKGROUND: The role of minimally invasive surgery using robotics versus laparoscopy in resectable gastric cancer patients with a high body mass index (BMI) remains controversial. METHODS: A total of 482 gastric adenocarcinoma patients with BMI ≥ 25 kg/m2 who underwent minimally invasive radical gastrectomy between August 2016 and December 2019 were retrospectively analyzed, including 109 cases in the robotic gastrectomy (RG) group and 321 cases in the laparoscopic gastrectomy (LG) group. Propensity score matching (PSM) with a 1:1 ratio was performed, and the perioperative outcomes, lymph node dissection, and 3-year overall survival (OS) and disease-free survival (DFS) rates were compared. RESULTS: After PSM, 109 patients were included in each of the RG and LG groups, with balanced baseline characteristics. Compared with the LG group, the RG group had similar intraoperative estimated blood loss [median (IQR) 30 (20-50) vs. 35 (30-59) mL, median difference (95%CI) - 5 (- 10 to 0)], postoperative complications [13.8% vs. 18.3%, OR (95%CI) 0.71 (0.342 to 1.473)], postoperative recovery, total harvested lymph nodes [(34.25 ± 13.43 vs. 35.44 ± 14.12, mean difference (95%CI) - 1.19 (- 4.871 to 2.485)] and textbook outcomes [(81.7% vs. 76.1%, OR (95%CI) 1.39 (0.724 to 2.684)]. Among pathological stage II-III patients receiving chemotherapy, the initiation of adjuvant chemotherapy in the RG group was similar to that in the LG group [median (IQR): 28 (25.5-32.5) vs. 32 (27-38.5) days, median difference (95%CI) - 3 (- 6 to 0)]. The 3-year OS (RG vs. LG: 80.7% vs. 81.7%, HR = 1.048, 95%CI 0.591 to 1.857) and DFS (78% vs. 76.1%, HR = 0.996, 95%CI 0.584 to 1.698) were comparable between the two groups. CONCLUSION: RG conferred comparable lymph node dissection, postoperative recovery, and oncologic outcomes in a selected cohort of patients with BMI ≥ 25 kg/m2.

Association between insulin receptor substrate 1 gene polymorphism rs1801278 and gestational diabetes mellitus: an updated meta- analysis.

OBJECTIVES: we performed this meta- analysis to investigate the impact of insulin receptor substrate 1 (IRS1) gene rs1801278 on susceptibility to gestational diabetes mellitus (GDM). METHODS: The pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated, and p value is used to determine statistical significance. Sensitivity analysis was performed under three models (dominant, recessive and allele model), and the pooled ORs and 95%CI were calculated. Funnel plots and Begger's regression test were employed to test the publication bias. RESULTS: The meta-analysis included 4777 participants (2116 cases and 2661 controls). The IRS1 rs1801278 (C/T) were not significant associated with GDM risk under the dominant and allele models, OR (95%CI) = 1.22 (0.88-1.70) and 1.24 (0.91-1.68), respectively (both p values were more than 0.05). But we also found the IRS1 rs1801278 (C/T) were significant associated with GDM risk under the recessive model, OR (95%CI) = 0.37 (0.16-0.86), p = 0.030. Our results showed that none of the studies affected the quality of the pooled OR. We also found no significant publication bias existed in this meta study for three genetic models, PTT + CT vs. CC = 0.445; PCC+CT vs. TT= 0.095; PC vs. T = 0.697. CONCLUSION: this meta-analysis indicated that IRS1 rs1801278 (C/T) was associated with the GDM risk under the recessive model but was not associated with the GDM risk under dominant and allele models.

Treatment opinions for dens invaginatus: A case series.

Dens invaginatus (DI) is a rare congenital dental malformation characterized by enamel or cementum folded into dentine. Such teeth are susceptible to caries, pulp infection or necrosis and periradicular lesion. The complex anatomy of this disease results in difficult treatment and a high rate of therapeutic failure. Therapeutic options, such as debriding and filling invagination, root canal treatment (RCT) and intentional replantation, vary according to the morphology and infection of the involved tooth. The present study reports five cases of DI with chronic apical periodontitis. The treatment strategies and procedures, including RCT, removing the invagination, intentional replantation and surgical treatment, are discussed according to the classification and the condition of pulp and periapical tissue. The study also reports the prognosis: All patients were followed up for ≥12 months and all teeth demonstrated periapical healing and clinical asymptomatic. In summary, appropriate treatment is based on accurate analysis of the anatomical variation in different types of DI and intentional replantation is a reliable and viable treatment to preserve the tooth.

Structures and organizations of PSI-AcpPCI supercomplexes from red tidal and coral symbiotic photosynthetic dinoflagellates.

Marine photosynthetic dinoflagellates are a group of successful phytoplankton that can form red tides in the ocean and also symbiosis with corals. These features are closely related to the photosynthetic properties of dinoflagellates. We report here three structures of photosystem I (PSI)-chlorophylls (Chls) a/c-peridinin protein complex (PSI-AcpPCI) from two species of dinoflagellates by single-particle cryoelectron microscopy. The crucial PsaA/B subunits of a red tidal dinoflagellate Amphidinium carterae are remarkably smaller and hence losing over 20 pigment-binding sites, whereas its PsaD/F/I/J/L/M/R subunits are larger and coordinate some additional pigment sites compared to other eukaryotic photosynthetic organisms, which may compensate for the smaller PsaA/B subunits. Similar modifications are observed in a coral symbiotic dinoflagellate Symbiodinium species, where two additional core proteins and fewer AcpPCIs are identified in the PSI-AcpPCI supercomplex. The antenna proteins AcpPCIs in dinoflagellates developed some loops and pigment sites as a result to accommodate the changed PSI core, therefore the structures of PSI-AcpPCI supercomplex of dinoflagellates reveal an unusual protein assembly pattern. A huge pigment network comprising Chls a and c and various carotenoids is revealed from the structural analysis, which provides the basis for our deeper understanding of the energy transfer and dissipation within the PSI-AcpPCI supercomplex, as well as the evolution of photosynthetic organisms.

Insights into the genetic variability and evolutionary dynamics of tomato spotted wilt orthotospovirus in China.

BACKGROUND: Viral diseases are posing threat to annual production and quality of tobacco in China. Recently, tomato spotted wilt orthotospovirus (TSWV) has been reported to infect three major crops including tobacco. Current study was aimed to investigate the population dynamics and molecular diversity of the TSWV. In the current study, to assess and identify the prevalence and evolutionary history of TSWV in tobacco crops in China, full-length genome sequences of TSWV isolates from tobacco, were identified and analyzed. METHODS: After trimming and validation, sequences of new isolates were submitted to GenBank. We identified the full-length genomes of ten TSWV isolates, infecting tobacco plants from various regions of China. Besides these, six isolates were partially sequenced. Phylogenetic analysis was performed to assess the relativeness of newly identified sequences and corresponding sequences from GenBank. Recombination and population dynamics analysis was performed using RDP4, RAT, and statistical estimation. Reassortment analysis was performed using MegaX software. RESULTS: Phylogenetic analysis of 41 newly identified sequences, depicted that the majority of the Chinese isolates have separate placement in the tree. RDP4 software predicted that RNA M of newly reported isolate YNKM-2 had a recombinant region spanning from 3111 to 3811 bp. The indication of parental sequences (YNKMXD and YNHHKY) from newly identified isolates, revealed the conservation of local TSWV population. Genetic diversity and population dynamics analysis also support the same trend. RNA M was highlighted to be more capable of mutating or evolving as revealed by data obtained from RDP4, RAT, population dynamics, and phylogenetic analyses. Reassortment analysis revealed that it might have happened in L segment of TSWV isolate YNKMXD (reported herein). CONCLUSION: Taken together, this is the first detailed study revealing the pattern of TWSV genetic diversity, and population dynamics helping to better understand the ability of this pathogen to drastically reduce the tobacco production in China. Also, this is a valuable addition to the existing worldwide profile of TSWV, especially in China, where a few studies related to TSWV have been reported including only one complete genome of this virus isolated from tobacco plants.

Non-transgenic, PAMAM co-delivery DNA of interactive proteins NbCRVP and NbCalB endows Nicotiana benthamiana with a stronger antiviral effect to RNA viruses.

BACKGROUND: Viral diseases continue to pose a major threat to the world's commercial crops. The in-depth exploration and efficient utilization of resistance proteins have become crucial strategies for their control. However, current delivery methods for introducing foreign DNA suffer from host range limitations, low transformation efficiencies, tissue damage, or unavoidable DNA integration into the host genome. The nanocarriers provides a convenient channel for the DNA delivery and functional utilization of disease-resistant proteins. RESULTS: In this research, we identified a cysteine-rich venom protein (NbCRVP) in Nicotiana benthamiana for the first time. Virus-induced gene silencing and transient overexpression clarified that NbCRVP could inhibit the infection of tobacco mosaic virus, potato virus Y, and cucumber mosaic virus, making it a broad-spectrum antiviral protein. Yeast two-hybrid assay, co-immunoprecipitation, and bimolecular fluorescence complementation revealed that calcium-dependent lipid-binding (CaLB domain) family protein (NbCalB) interacted with NbCRVP to assist NbCRVP playing a stronger antiviral effect. Here, we demonstrated for the first time the efficient co-delivery of DNA expressing NbCRVP and NbCalB into plants using poly(amidoamine) (PAMAM) nanocarriers, achieving stronger broad-spectrum antiviral effects. CONCLUSIONS: Our work presents a tool for species-independent transfer of two interacting protein DNA into plant cells in a specific ratio for enhanced antiviral effect without transgenic integration, which further demonstrated new strategies for nanocarrier-mediated DNA delivery of disease-resistant proteins.

Comparison of Short-Term Outcomes After Robotic Versus Laparoscopic Radical Gastrectomy for Advanced Gastric Cancer in Elderly Individuals: A Propensity Score-Matching Study.

BACKGROUND: Robotic gastrectomy (RG) has been widely used to treat gastric cancer. However, whether the short-term outcomes of robotic gastrectomy are superior to those of laparoscopic gastrectomy (LG) for elderly patients with advanced gastric cancer has not been reported. METHODS: The study enrolled of 594 elderly patients with advanced gastric cancer who underwent robotic or laparoscopic radical gastrectomy. The RG cohort was matched 1:3 with the LG cohort using propensity score-matching (PSM). RESULTS: After PSM, 121 patients were included in the robot group and 363 patients in the laparoscopic group. Excluding the docking and undocking times, the operation time of the two groups was similar (P = 0.617). The RG group had less intraoperative blood loss than the LG group (P < 0.001). The time to ambulation and first liquid food intake was significantly shorter in the RG group than in the LG group (P < 0.05). The incidence of postoperative complications did not differ significantly between the two groups (P = 0.14). Significantly more lymph nodes were dissected in the RG group than in the LG group (P = 0.001). Postoperative adjuvant chemotherapy was started earlier in the RG group than in the LG group (P = 0.02). CONCLUSIONS: For elderly patients with advanced gastric cancer, RG is safe and feasible. Compared with LG, RG is associated with less intraoperative blood loss; a faster postoperative recovery time, allowing a greater number of lymph nodes to be dissected; and earlier adjuvant chemotherapy.

Unraveling the regulatory network of miRNA expression in Potato Y virus-infected of Nicotiana benthamiana using integrated small RNA and transcriptome sequencing.

Potato virus Y (PVY) disease is a global problem that causes significant damage to crop quality and yield. As traditional chemical control methods are ineffective against PVY, it is crucial to explore new control strategies. MicroRNAs (miRNAs) play a crucial role in plant and animal defense responses to biotic and abiotic stresses. These endogenous miRNAs act as a link between antiviral gene pathways and host immunity. Several miRNAs target plant immune genes and are involved in the virus infection process. In this study, we conducted small RNA sequencing and transcriptome sequencing on healthy and PVY-infected N. benthamiana tissues (roots, stems, and leaves). Through bioinformatics analysis, we predicted potential targets of differentially expressed miRNAs using the N. benthamiana reference genome and the PVY genome. We then compared the identified differentially expressed mRNAs with the predicted target genes to uncover the complex relationships between miRNAs and their targets. This study successfully constructed a miRNA-mRNA network through the joint analysis of Small RNA sequencing and transcriptome sequencing, which unveiled potential miRNA targets and identified potential binding sites of miRNAs on the PVY genome. This miRNA-mRNA regulatory network suggests the involvement of miRNAs in the virus infection process.