Increased Attenuation of Intestinal Contents at CT Indicates Bowel Necrosis in Closed-Loop Small Bowel Obstruction.

Background Preoperative recognition of irreversible bowel necrosis is important, as it provides valuable guidance for surgical strategy selection but also may inform perioperative risk assessment and communication. Few studies have focused on the association between CT signs and bowel necrosis. Purpose To assess the diagnostic accuracy of CT signs to predict bowel necrosis in patients with closed-loop small bowel obstruction (CL-SBO). Materials and Methods This retrospective single-center study included patients who were surgically confirmed to have CL-SBO caused by adhesion or internal hernia between January 2016 and May 2022. Necrosis was determined based on surgical exploration and postoperative pathologic examination. Two radiologists independently reviewed CT signs by both subjective visual assessment and objective measurement. Disagreements were resolved in consensus with a third gastrointestinal radiologist. Univariable and multivariable analyses were used to assess the association between CT signs and bowel necrosis, and Cohen κ was used to assess interobserver agreement. Sensitivity and specificity were calculated for each CT sign. Results This study included 145 patients: 61 (42.1%) in the necrotic group (median age, 62 years [IQR, 51-71.5 years]; 37 [60.7%] women) and 84 (57.9%) in the nonnecrotic group (median age, 61.5 years [IQR, 51-68.8 years]; 51 [60.7%] women). Univariable analysis and multivariable analysis showed that increased attenuation of intestinal contents and increased attenuation of intestinal wall were independent predictors for bowel necrosis (odds ratio = 45.3 and 15.1; P = .001 and P < .001, respectively). Increased attenuation of intestinal contents and increased attenuation of intestinal wall had similar sensitivity (64% and 67%, respectively) and specificity (99% and 92%, respectively) for predicting bowel necrosis. However, interobserver agreement was better for assessing the contents than the wall (κ = 0.84 and 0.59, respectively). Conclusion Increased attenuation of intestinal contents was a highly specific CT sign with good reproducibility to predict bowel necrosis in CL-SBO. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Taourel and Zins in this issue.

Deletion of DP148R, DP71L, and DP96R Attenuates African Swine Fever Virus, and the Mutant Strain Confers Complete Protection against Homologous Challenges in Pigs.

The African swine fever virus (ASFV) has caused a devastating pandemic in domestic and wild swine, causing economic losses to the global swine industry. Recombinant live attenuated vaccines are an attractive option for ASFV treatment. However, safe and effective vaccines against ASFV are still scarce, and more high-quality experimental vaccine strains need to be developed. In this study, we revealed that deletion of the ASFV genes DP148R, DP71L, and DP96R from the highly virulent isolate ASFV CN/GS/2018 (ASFV-GS) substantially attenuated virulence in swine. Pigs infected with 104 50% hemadsorbing doses of the virus with these gene deletions remained healthy during the 19-day observation period. No ASFV infection was detected in contact pigs under the experimental conditions. Importantly, the inoculated pigs were protected against homologous challenges. Additionally, RNA sequence analysis showed that deletion of these viral genes induced significant upregulation of the host histone H3.1 gene (H3.1) and downregulation of the ASFV MGF110-7L gene. Knocking down the expression of H3.1 resulted in high levels of ASFV replication in primary porcine macrophages in vitro. These findings indicate that the deletion mutant virus ASFV-GS-Δ18R/NL/UK is a novel potential live attenuated vaccine candidate and one of the few experimental vaccine strains reported to induce full protection against the highly virulent ASFV-GS virus strain. IMPORTANCE Ongoing outbreaks of African swine fever (ASF) have considerably damaged the pig industry in affected countries. Thus, a safe and effective vaccine is important to control African swine fever spread. Here, an ASFV strain with three gene deletions was developed by knocking out the viral genes DP148R (MGF360-18R), NL (DP71L), and UK (DP96R). The results showed that the recombinant virus was completely attenuated in pigs and provided strong protection against parental virus challenge. Additionally, no viral genomes were detected in the sera of pigs housed with animals infected with the deletion mutant. Furthermore, transcriptome sequencing (RNA-seq) analysis revealed significant upregulation of histone H3.1 in virus-infected macrophage cultures and downregulation of the ASFV MGF110-7L gene after viral DP148R, UK, and NL deletion. Our study provides a valuable live attenuated vaccine candidate and potential gene targets for developing strategies for anti-ASFV treatment.

Tailoring Polyamide Nanofiltration Membranes by Switching Charge of Nanocellulose Interlayers.

The interlayer strategy has emerged as an effective approach for modulating the interfacial polymerization process and improving the permeability and selectivity of polyamide membranes. However, the underlying mechanisms by which charged interlayers influence the interfacial polymerization process remain inadequately understood. In this study, we utilized two distinct charged cellulose nanofibers, namely, carboxylated cellulose (⊖-CNF) and quaternized cellulose ([Formula: see text]-CNF), as interlayers to regulate the interfacial polymerization process. Through simulation results, isothermal titration calorimetry (ITC) and UV tests, we demonstrated that the [Formula: see text]-CNF interlayer, which possesses stronger hydration capability and better piperazine affinity, enhanced the diffusion of piperazine across the reaction interface compared with the ⊖-CNF interlayer. This led to an acceleration of the interfacial polymerization process and the formation of a denser membrane structure. Further investigation revealed that the charged interlayers significantly influenced the surface charging properties of the resulting nanofiltration membranes within a 30 nm range of electrostatic effects. Specifically, the ⊖-CNF interlayer conferred a higher negative charge to the membrane surface, while the [Formula: see text]-CNF interlayer endowed the membranes with a lower surface negative charge. Leveraging these differences, the ⊖-i-TFC membranes exhibited exceptional separation performance for divalent anions, achieving a SO42-/Cl- selectivity of 136. Conversely, the [Formula: see text]-i-TFC membrane demonstrated an enhanced separation of divalent cations, displaying a Mg2+/Na+ selectivity of 3.5. This study lays the groundwork for regulating the surface charging properties of polyamide membranes, offering potential advancements in nanofiltration applications.

The role of the immunoproteasome in cardiovascular disease.

The ubiquitinproteasome system (UPS) is the main mechanism responsible for the intracellular degradation of misfolded or damaged proteins. Under inflammatory conditions, the immunoproteasome, an isoform of the proteasome, can be induced, enhancing the antigen-presenting function of the UPS. Furthermore, the immunoproteasome also serves nonimmune functions, such as maintaining protein homeostasis and regulating signalling pathways, and is involved in the pathophysiological processes of various cardiovascular diseases (CVDs). This review aims to provide a comprehensive summary of the current research on the involvement of the immunoproteasome in cardiovascular diseases, with the ultimate goal of identifying novel strategies for the treatment of these conditions.

A meta-analysis comparing the diagnostic performance of computed tomography-derived fractional flow reserve and coronary computed tomography angiography at different levels of coronary artery calcium score.

OBJECTIVES: The impact of coronary calcification on the diagnostic accuracy of computed tomography-derived fractional flow reserve (CT-FFR) and coronary computed tomography angiography (CCTA) remains a crucial consideration. This meta-analysis aims to compare the diagnostic performance of CT-FFR and CCTA at different levels of coronary artery calcium score (CACS). METHODS AND RESULTS: We searched PubMed, Embase, and the Cochrane Library for relevant articles on CCTA, CT-FFR, and invasive fractional flow reserve (FFR). Ten studies were included to evaluate the diagnostic performance of CT-FFR and CCTA at the per-patient and per-vessel levels in four CACS groups. Invasive FFR was used as the reference standard. Except for the CACS ≥ 400 group, the AUC of CT-FFR was higher than those of CCTA in other subgroups of CACS (in CACS < 100 (per-patient, 0.9 (95% CI 0.87-0.92) vs. 0.32 (95% CI 0.28-0.36); per-vessel, 0.92 (95% CI 0.89-0.94) vs. 0.66 (95% CI 0.62-0.7); both p < 0.001), CACS ≥ 100 (per-patient, 0.86 (95% CI 0.82-0.88) vs. 0.44 (95% CI 0.4-0.48); per-vessel, 0.88 (95% CI 0.85-0.9) vs. 0.51 (95% CI 0.46-0.55); both p < 0.001), and CACS < 400 (per-patient, 0.9 (95% CI 0.87-0.93) vs. 0.74 (95% CI 0.7-0.78), p < 0.001; per-vessel, 0.8 (95% CI 0.76-0.83) vs. 0.74 (95% CI 0.7-0.78); p = 0.02)). CONCLUSIONS: CT-FFR demonstrates superior diagnostic performance in low CACS groups (CACS < 400) than CCTA in detecting hemodynamic stenoses in patients with coronary artery disease (CAD). CLINICAL RELEVANCE STATEMENT: Computed tomography-derived fractional flow reserve might be utilized to determine the necessity of invasive coronary angiography in coronary artery disease patients with coronary artery calcium score < 400. KEY POINTS: • There is a lack of meta-analysis comparing the diagnostic performance of computed tomography-derived fractional flow reserve and coronary computed tomography angiography at different levels of calcification. • Computed tomography-derived fractional flow reserve only has a better diagnostic performance than coronary computed tomography angiography with low amounts of coronary calcium. • For the low coronary artery calcium score group, computed tomography-derived fractional flow reserve might be a good non-invasive method to detect hemodynamic stenoses in coronary artery disease patients.

Multimedia Mercury Recovery from Coal-Fired Power Plants Utilizing N-Containing Conjugated Polymer Functionalized Fly Ash.

To recover multimedia mercury from coal-fired power plants, a novel N-containing conjugated polymer (polyaniline and polypyrrole) functionalized fly ash was prepared, which could continuously adsorb 99.2% of gaseous Hg0 at a high space velocity of 368,500 h-1 and nearly 100% of aqueous Hg2+ in the solution pH range of 2-12. The adsorption capacities of Hg0 and Hg2+ reach 1.62 and 101.36 mg/g, respectively. Such a kind of adsorbent has good environmental applicability, i.e. good resistance to coexisting O2/NO/SO2 and coexisting Na+/K+/Ca2+/Mg2+/SO42-. This adsorbent has very low specific resistances (6 × 106-5 × 109 Ω·cm) and thus can be easily collected by an electrostatic precipitator under low-voltage (0.1-0.8 kV). The Hg-saturated adsorbent can desorb almost 100% Hg under relatively low temperature (<250 °C). Characterization and theoretical calculations reveal that conjugated-N is the critical site for adsorbing both Hg0 and Hg2+ as well as activating chlorine. Gaseous Hg0 is oxidized and adsorbed in the form of HgXClX(ad), while aqueous Hg2+ is adsorbed to form a complex with conjugated-N, and parts of Hg2+ are reduced to Hg+ by conjugated-N. This adsorbent can be easily large-scale manufactured; thus, this novel solid waste functionalization method is promising to be applied in coal-fired power plants and other Hg-involving industrial scenes.

Electrochemical Reduction of Flue Gas Denitrification Wastewater to Ammonia Using a Dual-Defective Cu2O@Cu Heterojunction Electrode.

Wet flue gas denitrification offers a new route to convert industrial nitrogen oxides (NOx) into highly concentrated nitrate wastewater, from which the nitrogen resource can be recovered to ammonia (NH3) via electrochemical nitrate reduction reactions (NITRRs). Low-cost, scalable, and efficient cathodic materials need to be developed to enhance the NH3 production rate. Here, in situ electrodeposition was adopted to fabricate a foamy Cu-based heterojunction electrode containing both Cu-defects and oxygen vacancy loaded Cu2O (OVs-Cu2O), which achieved an NH3 yield rate of 3.59 mmol h-1 cm-2, NH3 Faradaic efficiency of 99.5%, and NH3 selectivity of 100%. Characterizations and theoretical calculations unveiled that the Cu-defects and OVs-Cu2O heterojunction boosted the H* yield, suppressed the hydrogen evolution reaction (HER), and served as dual reaction sites to coherently match the tandem reactions kinetics of NO3-to-NO2 and NO2-to-NH3. An integrated system was further built to combine wet flue gas denitrification and desulfurization, simultaneously converting NO and SO2 to produce the (NH4)2SO4 fertilizer. This study offers new insights into the application of low-cost Cu-based cathode for electrochemically driven wet denitrification wastewater valorization.

Discovery of novel 20S proteasome subunit ß5 PROTAC degraders as potential therapeutics for pharyngeal carcinoma and Bortezomib-resistant multiple myeloma.

Resistance to proteasome inhibitors like Bortezomib is a major challenge in the treatment of multiple myeloma (MM). Proteolysis targeting chimeras (PROTACs), an emerging therapeutic approach that induces selective degradation of target proteins, offer a promising solution to overcome drug resistance. In this study, we designed and synthesized novel small-molecule PROTACs that induce 20S proteasome subunit ß5 degradation as a strategy to overcome Bortezomib resistance. These 20S proteasome subunit ß5 PROTACs demonstrated considerable binding affinity to 20S proteasome subunit ß5 and cereblon (CRBN), effectively induced 20S proteasome subunit ß5 degradation, and exhibited potent antiproliferative activity against a panel of cancer cell lines. Notably, PROTACs 12f and 14 displayed robust antitumor effects against both the pharyngeal carcinoma cell line FaDu and the Bortezomib-resistant MM cell line KM3/BTZ in vitro and in vivo with excellent safety profiles. Taken together, our findings highlight the potential of PROTACs 12f and 14 as novel 20S proteasome subunit ß5-degrading agents for the treatment of pharyngeal carcinoma and overcoming Bortezomib resistance in MM.

Prevalence, predictors, and outcomes of acute respiratory distress syndrome in severe stroke.

OBJECTIVES: Patients with severe stroke are at high risk of developing acute respiratory distress syndrome (ARDS), but this severe complication was often under-diagnosed and rarely explored in stroke patients. We aimed to investigate the prevalence, early predictors, and outcomes of ARDS in severe stroke. METHODS: This prospective study included consecutive patients admitted to neurological intensive care unit (neuro-ICU) with severe stroke, including acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. The incidence of ARDS was examined, and baseline characteristics and severity scores on admission were investigated as potential early predictors for ARDS. The in-hospital mortality, length of neuro-ICU stay, the total cost in neuro-ICU, and neurological functions at 90 days were explored. RESULTS: Of 140 patients included, 35 (25.0%) developed ARDS. Over 90% of ARDS cases occurred within 1 week of admission. Procalcitonin (OR 1.310 95% CI 1.005-1.707, P = 0.046) and PaO2/FiO2 on admission (OR 0.986, 95% CI 0.979-0.993, P < 0.001) were independently associated with ARDS, and high brain natriuretic peptide (OR 0.994, 95% CI 0.989-0.998, P = 0.003) was a red flag biomarker warning that the respiratory symptoms may be caused by cardiac failure rather than ARDS. ARDS patients had longer stays and higher expenses in neuro-ICU. Among patients with ARDS, 25 (62.5%) were moderate or severe ARDS. All the patients with moderate to severe ARDS had an unfavorable outcome at 90 days. CONCLUSIONS: ARDS is common in patients with severe stroke, with most cases occurring in the first week of admission. Procalcitonin and PaO2/FiO2 on admission are early predictors of ARDS. ARDS worsens both short-term and long-term outcomes. The conflict in respiratory support strategies between ARDS and severe stroke needs to be further studied.

Tackling Few-Shot Challenges in Automatic Modulation Recognition: A Multi-Level Comparative Relation Network Combining Class Reconstruction Strategy.

Automatic Modulation Recognition (AMR) is a key technology in the field of cognitive communication, playing a core role in many applications, especially in wireless security issues. Currently, deep learning (DL)-based AMR technology has achieved many research results, greatly promoting the development of AMR technology. However, the few-shot dilemma faced by DL-based AMR methods greatly limits their application in practical scenarios. Therefore, this paper endeavored to address the challenge of AMR with limited data and proposed a novel meta-learning method, the Multi-Level Comparison Relation Network with Class Reconstruction (MCRN-CR). Firstly, the method designs a structure of a multi-level comparison relation network, which involves embedding functions to output their feature maps hierarchically, comprehensively calculating the relation scores between query samples and support samples to determine the modulation category. Secondly, the embedding function integrates a reconstruction module, leveraging an autoencoder for support sample reconstruction, wherein the encoder serves dual purposes as the embedding mechanism. The training regimen incorporates a meta-learning paradigm, harmoniously combining classification and reconstruction losses to refine the model's performance. The experimental results on the RadioML2018 dataset show that our designed method can greatly alleviate the small sample problem in AMR and is superior to existing methods.

MCML-BF: A Metal-Column Embedded Microstrip Line Transmission Structure with Bias Feeders for Beam-Scanning Leakage Antenna Design.

This article proposes a novel fixed-frequency beam scanning leakage antenna based on a liquid crystal metamaterial (LCM) and adopting a metal column embedded microstrip line (MCML) transmission structure. Based on the microstrip line (ML) transmission structure, it was observed that by adding two rows of metal columns in the dielectric substrate, electromagnetic waves can be more effectively transmitted to reduce dissipation, and attenuation loss can be lowered to improve energy radiation efficiency. This antenna couples TEM mode electromagnetic waves into free space by periodically arranging 72 complementary split ring resonators (CSRRs). The LC layer is encapsulated in the transmission medium between the ML and the metal grounding plate. The simulation results show that the antenna can achieve a 106° continuous beam turning from reverse -52° to forward 54° at a frequency of 38 GHz with the holographic principle. In practical applications, beam scanning is achieved by applying a DC bias voltage to the LC layer to adjust the LC dielectric constant. We designed a sector-blocking bias feeder structure to minimize the impact of RF signals on the DC source and avoid the effect of DC bias on antenna radiation. Further comparative experiments revealed that the bias feeder can significantly diminish the influence between the two sources, thereby reducing the impact of bias voltage introduced by LC layer feeding on antenna performance. Compared with existing approaches, the antenna array simultaneously combines the advantages of high frequency band, high gain, wide beam scanning range, and low loss.

Differences in rice component distribution across layers and their relationship with taste.

BACKGROUND: Rice taste is closely associated with endosperm composition, which varies among different rice layers. Although clarifying the relationship between this difference and nutritional taste can guide rice breeding and cultivation practices, research on this topic is limited. RESULTS: Here, typical rice varieties having excellent and poor taste characteristics were selected to analyze the distribution characteristics and differences of their components. The varieties with excellent taste exhibited lower apparent amylose content (AAC) and protein content (PC), lesser short-chain (Fa) and long-chain (Fb3 ) amylopectin (AP) and more medium-chain (Fb1+2 ) AP, higher long-to-short chain ratio (Fa:Fb3 ), and higher nitrogen (N), magnesium (Mg) and calcium (Ca) content in layer 1 (L1) than the varieties with poor taste. Layer 2 (L2) played a key role in AAC and PC regulation in the varieties with excellent taste by reducing AAC and appropriately increasing PC, consequently improving rice taste. AP structure in layer 3 (L3) substantially affected the taste of the two types of varieties. The mineral content was the highest in L1, and increased potassium (K), Ca, and Mg content improved taste in all varieties. CONCLUSION: AAC in each layer contributes to rice taste. PC and minerals primarily act on L1 and L2, whereas AP acts on L2 and L3. Therefore, the endosperm formation process should be exploited for improving rice taste. Furthermore, key resources and cultivation should be identified and regulated, respectively, to improve rice taste. © 2023 Society of Chemical Industry.

Real-World Effectiveness of Primary Series and Booster Doses of Inactivated Coronavirus Disease 2019 Vaccine Against Omicron BA.2 Variant Infection in China: A Retrospective Cohort Study.

BACKGROUND: China has been using inactivated coronavirus disease 2019 (COVID-19) vaccines as primary series and booster doses to protect the population from severe to fatal COVID-19. We evaluated primary and booster vaccine effectiveness (VE) against Omicron BA.2 infection outcomes. METHODS: This was a 13-province retrospective cohort study of quarantined close contacts of BA.2-infected individuals. Outcomes were BA.2 infection, COVID-19 pneumonia or worse, and severe/critical COVID-19. Absolute VE was estimated by comparison with an unvaccinated group. RESULTS: There were 289 427 close contacts ≥3 years old exposed to Omicron BA.2 cases; 31 831 turned nucleic acid amplification test-positive during quarantine, 97.2% with mild or asymptomatic infection, 2.6% with COVID-19 pneumonia, and 0.15% with severe/critical COVID-19. None died. Adjusted VE (aVE) against any infection was 17% for primary series and 22% when boosted. Primary series aVE in adults >18 years was 66% against COVID-19 pneumonia or worse and 91% against severe/critical COVID-19. Booster dose aVE was 74% against pneumonia or worse, and 93% against severe/critical COVID-19. CONCLUSIONS: Inactivated COVID-19 vaccines provided modest protection from infection, very good protection against pneumonia, and excellent protection against severe/critical COVID-19. Booster doses are necessary to provide strongest protection.

Polygonatum sibiricum component liquiritigenin restrains breast cancer cell invasion and migration by inhibiting HSP90 and chaperone-mediated autophagy.

Breast cancer (BC) is most commonly diagnosed worldwide. Liquiritigenin is a flavonoid found in various species of the Glycyrrhiza genus, showing anti-tumor activity. This article was to explore the influences of liquiritigenin on the biological behaviors of BC cells and its underlying mechanism. BC cells were treated with liquiritigenin alone or transfected with oe-HSP90 before liquiritigenin treatment. RT-qPCR and Western blotting were employed to examine the levels of HSP90, Snail, E-cadherin, HSC70, and LAMP-2A. Cell viability, proliferation, migration, and invasion were evaluated by performing MTT, colony formation, scratch, and Transwell assays, respectively. Liquiritigenin treatment reduced HSP90 and Snail levels and enhanced E-cadherin expression as well as inhibiting the proliferation, migration, and invasion of BC cells. Moreover, liquiritigenin treatment decreased the expression of HSC70 and LAMP-2A, proteins related to chaperone-mediated autophagy (CMA). HSP90 overexpression promoted the CMA, invasion, and migration of BC cells under liquiritigenin treatment. Liquiritigenin inhibits HSP90-mediated CMA, thereby suppressing BC cell growth.

Chirality Interplay between the Interior and Exterior of Metal-Organic Cages.

A series of metal-organic cages featuring two stereogenic elements, in terms of the twisting of amide moieties within the ligand backbones and the rotation of diazaanthracene segments along the ligand ridges, were exploited. These two chiral components are correlative and serve as relays for transmitting chirality information between the internal and external cages. The chirality information induced by a chiral guest inside the cage cavity can pass through the cage framework and influence the orientation of the diazaanthracene segments on the periphery of the cage. In turn, the chirality of a stereogenic center within the diazaanthracene segments can transfer back into the cavity, enabling discrimination of enantiomeric guests.

Development and Characterization of a Highly Selective Turn-On Fluorescent Ligand for ß3-Adrenergic Receptor.

For the precise visualization of GPCR, subtype selectivity of turn-on fluorescent ligands is of major relevance. Although there are many thriving ß-adrenergic receptors (ß-ARs) probes, none of them are selective to the ß3-subtype, which severely limits the development of ß3-AR investigations. Using a polyethylene glycol (PEG) chain to conjugate the Py-5 fluorophore with mirabegron, we present here a highly selective fluorescent ligand, H2, for ß3-AR. It was established by the radioligand and NanoLuc-based bioluminescence resonance energy transfer (NanoBRET) binding experiments that molecule H2 has a substantially higher affinity for ß3-AR than the other two subtypes (1/3, 45-fold; 2/3, 16-fold). More crucially, when molecule H2 was incubated with ß3-AR, the turn-on fluorescent signals could be quickly released. The subsequent investigations, which included cell imaging, tissue imaging, and flow-cytometry analysis, proved that molecule H2 may make it possible to quickly and accurately fluorescently identify ß3-AR at different levels. We offer a prospective fluorescent turn-on ligand with exceptional selectivity for ß3-AR as a result of our combined efforts.

Learning Curve of Robot-Assisted Lymph Node Dissection of the Left Recurrent Laryngeal Nerve: A Retrospective Study of 417 Patients.

OBJECTIVE: Left recurrent laryngeal nerve (no.106recL) lymph node dissection is a challenging procedure, and robotic-assisted minimally invasive esophagectomy (RAMIE) may have some advantages. This study aimed to determine the learning curve of no.106recL lymph node dissection. METHODS: The data of 417 patients who underwent McKeown RAMIE between June 2017 and June 2022 were retrospectively analyzed. The lymph node harvest of no.106recL was used to determine the learning curve, and the cumulative sum (CUSUM) method was employed to obtain the inflection point. RESULTS: A total of 404 patients (404/417, 96.9%) underwent robotic surgery. Based on the number of no.106recL lymph nodes harvested, the CUSUM learning curve was mapped and divided into three phases: phase I (1‒75 cases), phase II (76‒240 cases), and phase III (241‒404 cases). The median (IQR) number of no.106recL lymph node harvests were 1 (4), 3 (6,) and 4 (4) in each phase (p < 0.001). The lymph node dissection rate gradually increased from 62.7% in phase I to 82.9% in phase III (p = 0.001). The total and thoracic lymph node harvest gradually increased (p < 0.001), whereas operation time (p = 0.001) and blood loss gradually decreased (p < 0.001). Moreover, the incidence of total complication (p = 0.020) and recurrent laryngeal nerve injury (p = 0.001) significantly decreased, and the postoperative hospital stay gradually shortened (p < 0.001). CONCLUSION: Robotic no.106recL lymph node dissection has some advantages for patients with esophageal cancer. In this study, perioperative and clinical outcomes were significantly improved over the learning curve. However, further prospective studies are required to confirm our results.

Real-world practice of conversion surgery for unresectable hepatocellular carcinoma - a single center data of 26 consecutive patients.

AIM: To understand the proportion of uHCC (unresectable hepatocellular carcinoma) patients who achieve successful conversion resection in a high-volume setting with state of the art treatment options. METHODS: We retrospectively reviewed all HCC patients hospitalized to our center from June 1st, 2019 to June 1st, 2022. Conversion rate, clinicopathological features, response to systemic and/or loco-regional therapy and surgical outcomes were analyzed. RESULTS: A total of 1,904 HCC patients were identified, with 1672 patients receiving anti-HCC treatment. 328 patients were considered up-front resectable. Of the remaining 1344 uHCC patients, 311 received loco-regional treatment, 224 received systemic treatment, and the remainder (809) received combination systemic plus loco-regional treatment. Following treatment, one patient from the systemic group and 25 patients from the combination group were considered to have resectable disease. A high objective response rate (ORR) was observed in these converted patients (42.3% under RECIST v1.1 and 76.9% under mRECIST criteria). The disease control rate (DCR) reached 100%. 23 patients underwent curative hepatectomy. Major post-operative morbidity was equivalent in the both groups (P=0.76). Pathologic complete response (pCR) was 39.1%. During conversion treatment, grade 3 or higher treatment-related adverse events (TRAEs) were observed in 50% of patients. The median follow-up time was 12.9 months (range, 3.9~40.6) from index diagnosis and 11.4 months (range, 0.9~26.9) from resection. Three patients experienced disease recurrence following conversion surgery. CONCLUSIONS: By intensive treatment, a small sub-group of uHCC patients (2%) may potentially be converted to curative resection. Loco-regional combined with systemic modality was relative safe and effective in the conversion therapy. Short-term outcomes are encouraging, but long-term follow-up in a larger patient population are required to fully understand the utility of this approach.

CCND1-Induced Autophagy Contributes to Lymph Node Metastasis in Endometrial Cancer.

Endometrial cancer with lymph node metastasis shows poor prognosis, while the biomarker to predict the metastasis is lacking. The relative mRNA or protein expression of cyclin D1 (CCND1) and autophagy-related molecules were detected in real-time PCR and Western blot. Correlation analysis was applied to identify any significant patterns, and receiver operating characteristics (ROC) was performed to assess the prediction value. CCND1 vector was transfected in Ishikawa (ISK) cells, and the relative expression of autophagy-related molecules was detected with Western blot. CCND1 was overexpressed in endometrial cancer and correlated with lymph node metastasis. ROC analysis found that CCND1 had a predictive value to discriminate tumors from normal tissues (cut off=1.455; sensitivity, 71%; specificity, 84%; area under curve (AUC) 0.82; p<0.001) and had a predictive value to indicate metastasis (cut off=1.871; sensitivity, 54.17%; specificity, 75%; AUC 0.674; p=0.003). Increased BECLIN1 (r=0.39, p<0.001) and ATG5 (r=0.41, p<0.001) expression were positively correlated to CCND1. On the other hand, the relative protein expression of CCND1, BECLIN1, ATG5, ATG7, and LC3 I/II were also increased in tumor tissues. CCND1 overexpressed ISK cells showed upregulated BECLIN1, ATG5, ATG7, and LC3 I/II expression. CCND1 promoted autophagy may contribute to lymph node metastasis in endometrial cancer.

African Swine Fever Virus MGF-505-7R Negatively Regulates cGAS-STING-Mediated Signaling Pathway.

African swine fever virus (ASFV) is a devastating infectious disease in pigs, severely threatening the global pig industry. To efficiently infect animals, ASFV must evade or inhibit fundamental elements of the innate immune system, namely the type I IFN response. In this study, we identified that ASFV MGF-505-7R protein exerts a negative regulatory effect on STING-dependent antiviral responses. MGF-505-7R interacted with STING and inhibited the cGAS-STING signaling pathway at STING level. MGF-505-7R overexpression either degraded STING or STING expression was reduced in ASFV-infected cells via autophagy, whereas STING expression was elevated in MGF-505-7R-deficient ASFV-infected cells. We further found that MGF-505-7R promoted the expression of the autophagy-related protein ULK1 to degrade STING, whereas ULK1 was elevated in MGF-505-7R-deficient ASFV-infected cells. Moreover, MGF-505-7R-deficient ASFV induced more IFN-ß production than wild-type ASFV and was attenuated in replication compared with wild-type ASFV. The replicative ability of MGF-505-7R-deficient ASFV was also attenuated compared with wild-type. Importantly, MGF-505-7R-deficient ASFV was fully attenuated in pigs. Our results showed for the first time, to our knowledge, a relationship involving the cGAS-STING pathway and ASFV MGF-505-7R, contributing to uncover the molecular mechanisms of ASFV virulence and to the rational development of ASFV vaccines.