Recent advances on anti-HIV chimeric antigen receptor-T-cell treatment to provide sustained HIV remission.

PURPOSE OF REVIEW: Successful sustained remission of HIV infection has been achieved after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation for treatment of leukemia in a small cohort of people living with HIV (PLWH). This breakthrough demonstrated that the goal of curing HIV was achievable. However, the high morbidity and mortality associated with bone marrow transplantation limits the routine application of this approach and provides a strong rationale for pursuing alternative strategies for sustained long-term antiretroviral therapy (ART)-free HIV remission. Notably, long-term immune-mediated control of HIV replication observed in elite controllers and posttreatment controllers suggests that potent HIV-specific immune responses could provide sustained ART-free remission in PLWH. The capacity of chimeric antigen receptor (CAR)-T cells engineered to target malignant cells to induce remission and cure in cancer patients made this an attractive approach to provide PLWH with a potent HIV-specific immune response. Here, we review the recent advances in the design and application of anti-HIV CAR-T-cell therapy to provide a functional HIV cure. RECENT FINDINGS: HIV reservoirs are established days after infection and persist through clonal expansion of infected cells. The continuous interaction between latently infected cells and the immune system shapes the landscape of HIV latency and likely contributes to ART-free viral control in elite controllers. CAR-T cells can exhibit superior antiviral activity as compared with native HIV-specific T cells, particularly because they can be engineered to have multiple HIV specificities, resistance to HIV infection, dual costimulatory signaling, immune checkpoint inhibitors, stem cell derivation, CMV TCR coexpression, and tissue homing ligands. These modifications can significantly improve the capacities of anti-HIV CAR-T cells to prevent viral escape, resist HIV infection, and enhance cytotoxicity, persistence, and tissue penetration. Collectively, these novel modifications of anti-HIV CAR-T cell design have increased their capacity to control HIV infection. SUMMARY: Anti-HIV CAR-T cells can be engineered to provide potent and sustained in-vitro and in-vivo antiviral function. The combination of anti-HIV CAR-T cells with other immunotherapeutics may contribute to long-term HIV remission in PLWH.

Generation of Anti-HIV CAR-T Cells for Preclinical Research.

The inability of people living with HIV (PLWH) to eradicate human immunodeficiency virus (HIV) infection is due in part to the inadequate HIV-specific cellular immune response. The antiviral function of cytotoxic CD8+ T cells, which are crucial for HIV control, is impaired during chronic viral infection because of viral escape mutations, immune exhaustion, HIV antigen downregulation, inflammation, and apoptosis. In addition, some HIV-infected cells either localize to tissue sanctuaries inaccessible to CD8+ T cells or are intrinsically resistant to CD8+ T cell killing. The novel design of synthetic chimeric antigen receptors (CARs) that enable T cells to target specific antigens has led to the development of potent and effective CAR-T cell therapies. While initial clinical trials using anti-HIV CAR-T cells performed over 20 years ago showed limited anti-HIV effects, the improved CAR-T cell design, which enabled its success in treating cancer, has reinstated CAR-T cell therapy as a strategy for HIV cure with notable progress being made in the recent decade.Effective CAR-T cell therapy against HIV infection requires the generation of anti-HIV CAR-T cells with potent in vivo activity against HIV-infected cells. Preclinical evaluation of anti-HIV efficacy of CAR-T cells and their safety is fundamental for supporting the initiation of subsequent clinical trials in PLWH. For these preclinical studies, we developed a novel humanized mouse model supporting in vivo HIV infection, the development of viremia, and the evaluation of novel HIV therapeutics. Preclinical assessment of anti-HIV CAR-T cells using this mouse model involves a multistep process including peripheral blood mononuclear cells (PBMCs) harvested from human donors, T cell purification, ex vivo T cell activation, transduction with lentiviral vectors encoding an anti-HIV CAR, CAR-T cell expansion and infusion in mice intrasplenically injected with autologous PBMCs followed by the determination of CAR-T cell capacity for HIV suppression. Each of the steps described in the following protocol were optimized in the lab to maximize the quantity and quality of the final anti-HIV CAR-T cell products.

Exploring the Potential of Biochar Derived from Chinese Herbal Medicine Residue for Efficient Removal of Norfloxacin.

One-step carbonization was explored to prepare biochar using the residue of a traditional Chinese herbal medicine, Atropa belladonna L. (ABL), as the raw material. The resulting biochar, known as ABLB4, was evaluated for its potential as a sustainable material for norfloxacin (NOR) adsorption in water. Subsequently, a comprehensive analysis of adsorption isotherms, kinetics, and thermodynamics was conducted through batch adsorption experiments. The maximum calculated NOR adsorption capacity was 252.0 mg/g at 298 K, and the spontaneous and exothermic adsorption of NOR on ABLB4 could be better suited to a pseudo-first-order kinetic model and Langmuir model. The adsorption process observed is influenced by pore diffusion, π-π interaction, electrostatic interaction, and hydrogen bonding between ABLB4 and NOR molecules. Moreover, the utilization of response surface modeling (RSM) facilitated the optimization of the removal efficiency of NOR, yielding a maximum removal rate of 97.4% at a temperature of 304.8 K, an initial concentration of 67.1 mg/L, and a pH of 7.4. Furthermore, the biochar demonstrated favorable economic advantages, with a payback of 852.5 USD/t. More importantly, even after undergoing five cycles, ABLB4 exhibited a consistently high NOR removal rate, indicating its significant potential for application in NOR adsorption.

Efficacy of chidamide maintenance therapy versus autologous stem cell transplantation versus observation as a post-remission choice in the survival of adult patients with peripheral T-cell lymphoma: Post hoc analysis of a prospective, multicenter, phase 2 study in China.

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

Urolithin A's Role in Alleviating Severe Acute Pancreatitis via Endoplasmic Reticulum-Mitochondrial Calcium Channel Modulation.

Severe acute pancreatitis (SAP), characterized by pancreatic acinar cell death, currently lacks effective targeted therapies. Ellagic acid (EA), rich in pomegranate, shows promising anti-inflammatory and antioxidant effects in SAP treatment. However, the roles of other forms of EA, such as plant extracellular vesicles (EVs) extracted from pomegranate, and Urolithin A (UA), converted from EA through gut microbiota metabolism in vivo, have not been definitively elucidated. Our research aimed to compare the effects of pomegranate-derived EVs (P-EVs) and UA in the treatment of SAP to screen an effective formulation and to explore its mechanisms in protecting acinar cells in SAP. By comparing the protective effects of P-EVs and UA on injured acinar cells, UA showed superior therapeutic effects than P-EVs. Subsequently, we further discussed the mechanism of UA in alleviating SAP inflammation. In vivo animal experiments found that UA could not only improve the inflammatory environment of pancreatic tissue and peripheral blood circulation in SAP mice but also revealed that the mechanism of UA in improving SAP might be related to mitochondria and endoplasmic reticulum (ER) through the results including pancreatic tissue transcriptomics and transmission electron microscopy. Further research found that UA could regulate ER-mitochondrial calcium channels and reduce pancreatic tissue necroptosis. In vitro experiments of mouse pancreatic organoids and acinar cells also confirmed that UA could improve pancreatic inflammation by regulating the ER-mitochondrial calcium channel and necroptosis pathway proteins. This study not only explored the therapeutic effect of plant EVs on SAP but also revealed that UA could alleviate SAP by regulating ER-mitochondrial calcium channel and reducing acinar cell necroptosis, providing insights into the pathogenesis and potential treatment of SAP.

Prediction of martensite start temperature of steel combined with expert experience and machine learning.

The martensite start temperature (MS) plays a pivotal role in formulating heat treatment regimes for steel. This paper, through the compilation of experimental data from literature and the incorporation of expert knowledge to construct features, employs machine learning algorithms to predict the MS of steel. The study highlights that the ETR algorithm attains optimal prediction accuracy, and the inclusion of atomic features enhances the model's performance. Feature selection is accomplished by evaluating linear and nonlinear relationships between data using the Pearson correlation coefficient (PCC), variance inflation factor (VIF), and maximum information coefficient (MIC). Subsequently, the performance of machine learning models on unknown data is compared to validate the model's generalization ability. The introduction of SHAP values for model interpretability analysis unveils the influencing mechanisms between features and the target variable. Finally, utilizing a specific steel type as an illustration, the paper underscores the practical value of the model.

This study innovatively integrates experimental data, expert knowledge, and ETR algorithm for accurate MS prediction in steel, enhancing model performance with systematic feature selection and interpretability analysis, demonstrating practical utility.

Neuroendocrine carcinoma of the common hepatic duct coexisting with distal cholangiocarcinoma: A case report and review of literature.

BACKGROUND: Neuroendocrine carcinoma (NEC) of the extrahepatic bile duct is very rare, and the treatment and prognosis are unclear. Herein, we report the case of a middle-aged female with primary large cell NEC (LCNEC) of the common hepatic duct combined with distal cholangiocarcinoma (dCCA). Additionally, after a review of the relevant literature, we summarize and compare mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) and pure NEC to provide a reference for selecting the appropriate treatment and predicting the prognosis of this rare disease. CASE SUMMARY: A 62-year-old female presented to the hospital due to recurrent abdominal pain for 2 months. Physical examination showed mild tenderness in the upper abdomen and a positive Courvoisier sign. Blood tests showed elevated liver transaminase and carbohydrate antigen 199 levels. Imaging examination revealed a 1-cm tumour in the middle and lower segments of the common bile duct. Pancreaticoduodenectomy + lymph node dissection was performed, and hepatic duct tumours were unexpectedly found during surgery. Pathology suggested poorly differentiated LCNEC (approximately 0.5 cm × 0.5 cm × 0.4 cm), Ki-67 (50%), synaptophysin+, and chromogranin A+. dCCA pathology suggested moderately differentiated adenocarcinoma. The patient eventually developed lymph node metastasis in the liver, bone, peritoneum, and abdominal cavity and died 24 months after surgery. Gene sequencing methods were used to compare gene mutations in the two primary bile duct tumours. CONCLUSION: The prognosis of MiNEN and pure NEC alone is different, and the selection of treatment options needs to be differentiated.

Reducing Soil-Emitted Nitrous Acid as a Feasible Strategy for Tackling Ozone Pollution.

Severe ozone (O3) pollution has been a major air quality issue and affects environmental sustainability in China. Conventional mitigation strategies focusing on reducing volatile organic compounds and nitrogen oxides (NOx) remain complex and challenging. Here, through field flux measurements and laboratory simulations, we observe substantial nitrous acid (HONO) emissions (FHONO) enhanced by nitrogen fertilizer application at an agricultural site. The observed FHONO significantly improves model performance in predicting atmospheric HONO and leads to regional O3 increases by 37%. We also demonstrate the significant potential of nitrification inhibitors in reducing emissions of reactive nitrogen, including HONO and NOx, by as much as 90%, as well as greenhouse gases like nitrous oxide by up to 60%. Our findings introduce a feasible concept for mitigating O3 pollution: reducing soil HONO emissions. Hence, this study has important implications for policy decisions related to the control of O3 pollution and climate change.

A dual-responsive RhB-doped MOF probe for simultaneous recognition of Cu2+ and Fe3.

Based on the dual response of RhB@UiO-67 (1:6) to Cu2+ and Fe3+, a proportional fluorescent probe with (I392/I581) as the output signal was developed to recognize Cu2+ and Fe3+. Developing highly sensitive and selective trace metal ions probes is crucial to human health and ecological sustainability. In this work, a series of ratio fluorescent probes (RhB@UiO-67) were successfully synthesized using a one-pot method to enable fluorescence sensing of Cu2+ and Fe3+ at low concentrations. The proportional fluorescent probe RhB@UiO-67 (1:6) exhibited simultaneous quenching of Cu2+ and Fe3+, which was found to be of interest. Furthermore, the limits of detection (LODs) for Cu2+ and Fe3+ were determined to be 2.76 µM and 0.76 µM, respectively, for RhB@UiO-67 (1:6). These values were significantly superior to those reported for previous sensors, indicating the probe's effectiveness in detecting Cu2+ and Fe3+ in an ethanol medium. Additionally, RhB@UiO-67 (1:6) demonstrated exceptional immunity and reproducibility towards Cu2+ and Fe3+. The observed fluorescence quenching of Cu2+ and Fe3+ was primarily attributed to the mechanisms of fluorescence resonance energy transfer (FRET), photoinduced electron transfer (PET), and competitive absorption (CA). This work establishes a valuable foundation for the future study and utilization of Cu2+ and Fe3+ sensing technologies.

The Long Hazy Tail: Analysis of the Impacts and Trends of Severe Outdoor and Indoor Air Pollution in North China.

China, especially the densely populated North China region, experienced severe haze events in the past decade that concerned the public. Although the most extreme cases have been largely eliminated through recent mitigation measures, severe outdoor air pollution persists and its environmental impact needs to be understood. Severe indoor pollution draws less public attention due to the short visible distance indoors, but its public health impacts cannot be ignored. Herein, we assess the trends and impacts of severe outdoor and indoor air pollution in North China from 2014 to 2021. Our results demonstrate the uneven contribution of severe hazy days to ambient and exposure concentrations of particulate matter with an aerodynamic diameter <2.5 (PM2.5). Although severe indoor pollution contributes to indoor PM2.5 concentrations (23%) to a similar extent as severe haze contributes to ambient PM2.5 concentrations (21%), the former's contribution to premature deaths was significantly higher. Furthermore, residential emissions contributed more in the higher PM2.5 concentration range both indoors and outdoors. Notably, severe haze had greater health impacts on urban residents, while severe indoor pollution was more impactful in rural areas. Our findings suggest that, besides reducing severe haze, mitigating severe indoor pollution is an important aspect of combating air pollution, especially toward improving public health.

Toxicokinetics Explain Differential Freshwater Ecotoxicity of Nanoencapsulated Imidacloprid Compared to Its Conventional Active Ingredient.

Agricultural applications of nanotechnologies necessitate addressing safety concerns associated with nanopesticides, yet research has not adequately elucidated potential environmental risks between nanopesticides and their conventional counterparts. To address this gap, we investigated the risk of nanopesticides by comparing the ecotoxicity of nanoencapsulated imidacloprid (nano-IMI) with its active ingredient to nontarget freshwater organisms (embryonic Danio rerio, Daphnia magna, and Chironomus kiinensis). Nano-IMI elicited approximately 5 times higher toxicity than IMI to zebrafish embryos with and without chorion, while no significant difference was observed between the two invertebrates. Toxicokinetics further explained the differential toxicity patterns of the two IMI analogues. One-compartmental two-phase toxicokinetic modeling showed that nano-IMI exhibited significantly slower elimination and subsequently higher bioaccumulation potential than IMI in zebrafish embryos (dechorinated), while no disparity in toxicokinetics was observed between nano-IMI and IMI in D. magna and C. kiinensis. A two-compartmental toxicokinetic model successfully simulated the slow elimination of IMI from C. kiinensis and confirmed that both analogues of IMI reached toxicologically relevant targets at similar levels. Although nanopesticides exhibit comparable or elevated toxicity, future work is of utmost importance to properly understand the life cycle risks from production to end-of-life exposures, which helps establish optimal management measures before their widespread applications.

A novel mechanism of major ginsenosides from Panax ginseng against multiple organ aging in middle-aged mice: Phosphatidylcholine-myo-inositol metabolism based on metabolomic analysis.

Aging is a complex, degenerative process associated with various metabolic abnormalities. Ginsenosides (GS) is the main active components of Panax ginseng, which has anti-aging effects and improves metabolism. However, the anti-aging effect and the mechanism of GS in middle-aged mice has not been elucidated. In this study, GS after 3-month treatment significantly improved the grip strength, fatigue resistance, cognitive indices, and cardiac function of 15-month-old mice. Meanwhile, GS treatment reduced the fat content and obviously inhibited histone H2AX phosphorylation at Ser 139 (γ-H2AX), a marker of DNA damage in major organs, especially in the heart and liver. Further, the correlation analysis of serum metabolomics combined with aging phenotype suggested that myo-inositol (MI) upregulated by GS was positively correlated with left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), the main indicators of cardiac function. More importantly, liver tissue metabolomic analysis showed that GS increased MI content by promoting the synthesis pathway from phosphatidylcholine (PC) to MI for the inhibition of liver aging. Finally, we proved that MI reduced the percentage of senescence-associated ß-galactosidase staining, γ-H2AX immunofluorescence staining, p21 expression, and the production of reactive oxygen species in H2O2-induced cardiomyocytes. These results suggest that GS can enhance multiple organ functions, especially cardiac function for promoting the healthspan of aging mice, which is mediated by the conversion of PC to MI in the liver and the increase of MI level in the serum. Our study might provide new insights into the potential mechanisms of ginsenosides for prolonging the healthspan of natural aging mice.

Glued-bamboo composite based on a highly cross-linked cellulose-based adhesive and an epoxy functionalized bamboo surface.

Bamboo, as a renewable bioresource, exhibits advantages of fast growth cycle and high strength. Bamboo-based composite materials are a promising alternative to load-bearing structural materials. It is urgent to develop high-performance glued-bamboo composite materials. This study focused on the chemical bonding interface to achieve high bonding strength and water resistance between bamboo and dialdehyde cellulose-polyamine (DAC-PA4N) adhesive by activating the bamboo surface. The bamboo surface was initially modified in a directional manner to create an epoxy-bamboo interface using GPTES. The epoxy groups on the interface were then chemically crosslinked with the amino groups of the DAC-PA4N adhesive, forming covalent bonds within the adhesive layer. The results demonstrated that the hot water strength of the modified bamboo was improved by 75.8 % (from 5.17 to 9.09 MPa), and the boiling water strength was enhanced by 232 % (from 2.10 to 6.99 MPa). The bonding and flexural properties of this work are comparable to those of commercial phenolic resin. The activation modification of the bamboo surface offers a novel approach to the development of low-carbon, environmentally friendly, and sustainable bamboo engineering composites.

Automated extraction of Tridacna shell growth patterns via machine learning for enhanced paleoclimate/paleoweather research.

Tridacna spp. are valuable archives for paleoclimate and paleoweather research due to their distinct daily growth patterns and the sensitivity of the daily growth patterns to environment changes. However, manually identifying daily growth lines and measuring the daily growth increment width (DGIW) of Tridacna shells from Laser Scanning Confocal Microscopy (LSCM) images is a tedious task that has become a significant barrier to Tridacna studies. This paper addresses this challenge by integrating machine learning into Tridacna research for the first time to automate the calculation of the number of daily growth lines and DGIW of Tridacna shells. Specifically, we propose an unsupervised generative adversarial attention network called TriGAN to automatically recognize distinct daily growth lines of Tridacna shells from LSCM images. Utilizing modern Tridacna specimens collected from the South China Sea, our experimental results demonstrate that TriGAN can effectively reconstruct the ambiguous and blurred regions in LSCM images and produce higher quality images of daily growth patterns compared to existing image generation networks. Furthermore, the daily growth line number and DGIW of Tridacna shells can be counted automatically from the images recognized by TriGAN, which are in good agreement with the statistical results obtained manually from the original LSCM images (R = 0.7, p < 0.01 for the DGIW profile of T. gigas specimen MD1 and R = 0.6, p < 0.01 for T. derasa specimen XB10). This automated method provides an efficient solution for researching the laminar chronology of Tridacna.

Primary catastrophic antiphospholipid syndrome in children with midbrain infarction: a case report.

Background: Catastrophic antiphospholipid syndrome (CAPS) is a multi-system autoimmune disease characterized by extensive thrombosis. Pediatric CAPS is extremely rare and associated with a high mortality rate, especially when midbrain infarction is involved. Hence, early diagnosis and prompt initiation of appropriate treatment for CAPS complicated by midbrain infarction are of utmost importance in achieving favorable outcomes. Case presentation: In this report, we present the case of a 14-year-old girl who presented with neurological symptoms and digestive system infection and was initially diagnosed with an "intracranial infection". After a series of rigorous diagnostic procedures, the patient was ultimately diagnosed with primary CAPS and was immediately transferred to the intensive care unit where she was treated with anticoagulation, glucocorticoids, intravenous immunoglobulin (IVIG) therapy, and multiple plasma infusions. Twenty-seven days after admission, the patient's condition improved with standardized treatment, and she was discharged and followed up regularly. Conclusion: This case report provides a description of the clinical features observed in a pediatric patient with CAPS and concurrent midbrain infarction, highlighting the crucial role of early diagnosis and timely treatment in influencing patient prognosis.

Phase II study of novel orally PI3Kα/δ inhibitor TQ-B3525 in relapsed and/or refractory follicular lymphoma.

This registration study assessed clinical outcomes of TQ-B3525, the dual phosphatidylinositol-3-kinase (PI3K) α/δ inhibitor, in relapsed and/or refractory follicular lymphoma (R/R FL). This phase II study (ClinicalTrials.gov NCT04324879. Registered March 27, 2020) comprised run-in stage and stage 2. R/R FL patients after ≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR). Based on results (ORR, 88.0%; duration of response [DOR], 11.8 months; progression-free survival [PFS], 12.0 months) in 25 patients at run-in stage, second stage study was initiated and included 82 patients for efficacy/safety analysis. Patients received prior-line (median, 3) therapies, with 56.1% refractory to previous last therapies; 73.2% experienced POD24 at baseline. At stage 2, ORR was 86.6% (71/82; 95% CI, 77.3-93.1%), with 28 (34.2%) complete responses. Disease control rate was 95.1% due to 7 (8.5%) stable diseases. Median time to response was 1.8 months. Among 71 responders, median DOR was not reached; 18-month DOR rate was 51.6%. with median follow-up of 13.3 months, median PFS was 18.5 (95% CI, 10.2-not estimable) months. Median overall survival (OS) was not reached by cutoff date; 24-month OS rate was estimated as 86.1%. Response rates and survival data were consistent across all subgroups. Grade 3 or higher treatment-related adverse events were observed in 63 (76.8%) cases, with neutropenia (22.0%), hyperglycemia (19.5%), and diarrhea (13.4%) being common. TQ-B3525 showed favorable efficacy and safety for R/R FL patients after ≥2 lines prior therapies.

Ultrahigh energy storage in high-entropy ceramic capacitors with polymorphic relaxor phase.

Ultrahigh-power-density multilayer ceramic capacitors (MLCCs) are critical components in electrical and electronic systems. However, the realization of a high energy density combined with a high efficiency is a major challenge for practical applications. We propose a high-entropy design in barium titanate (BaTiO3)-based lead-free MLCCs with polymorphic relaxor phase. This strategy effectively minimizes hysteresis loss by lowering the domain-switching barriers and enhances the breakdown strength by the high atomic disorder with lattice distortion and grain refining. Benefiting from the synergistic effects, we achieved a high energy density of 20.8 joules per cubic centimeter with an ultrahigh efficiency of 97.5% in the MLCCs. This approach should be universally applicable to designing high-performance dielectrics for energy storage and other related functionalities.

Limited resection is comparable to lobectomy for tumor size ≤ 2 cm pulmonary invasive mucinous adenocarcinoma.

OBJECTIVES: Invasive mucinous adenocarcinoma (IMA) has a rare incidence with better prognosis than nonmucinous adenocarcinoma. We aimed to investigate the prognosis between limited resection and lobectomy for patients with clinical stage IA IMA ≤ 2 cm. METHODS: Data were taken from two cohorts: In Shanghai Pulmonary Hospital (SPH) corhort, we identified 403 patients with clinical stage IA IMA who underwent surgery. In the SEER corhort, 480 patients with stage T1 IMA who after surgery were included. Recurrence-free survival (RFS) for SPH corhort, lung cancer-specific survival (LCSS) for the SEER corhort and overall survival (OS) for both corhort were compared between patients undergoing lobectomy and limited resection by Log-rank and Cox proportional hazard regression model. RESULTS: In SPH corhort, patients who underwent limited resection had equivalent prognosis than those underwent lobectomy (5-year RFS: 79.3% versus. 82.6%, p = 0.116; 5-year OS: 86.2% versus. 88.3%, p = 0.235). However, patients with IMA > 2 to 3 cm had worse prognosis than those with IMA ≤ 2 cm (5-year RFS: 73.7% versus. 86.1%, p = 0.007). In the analysis of IMA > 2 to 3 cm subgroup, multivariate analysis showed that limited resection was an independent risk factor of RFS (hazard ratio, 2.417; 95% confidence interval, 1.157-5.049; p = 0.019), while OS (p = 0.122) was not significantly different between two groups. For IMA ≤ 2 cm, limited resection was not a risk factor of RFS (p = 0. 953) and OS (p = 0.552). In the SEER corhort, IMA ≤ 2 cm subgroup, limited resection was equivalent prognosis in LCSS (p = 0.703) and OS (p = 0.830). CONCLUSIONS: Limited resection could be a potential surgical option which comparable to lobectomy in patients with clinical stage IA IMA ≤ 2 cm.

Alginate oligosaccharide assimilation by gut microorganisms and the potential role in gut inflammation alleviation.

Dietary fiber metabolism by gut microorganisms plays important roles in host physiology and health. Alginate, the major dietary fiber of daily diet seaweeds, is drawing more attention because of multiple biological activities. To advance the understanding of alginate assimilation mechanism in the gut, we show the presence of unsaturated alginate oligosaccharides (uAOS)-specific alginate utilization loci (AUL) in human gut microbiome. As a representative example, a working model of the AUL from the gut microorganism Bacteroides clarus was reconstructed from biochemistry and transcriptome data. The fermentation of resulting monosaccharides through Entner-Doudoroff pathway tunes the metabolism of short-chain fatty acids and amino acids. Furthermore, we show that uAOS feeding protects the mice against dextran sulfate sodium-induced acute colitis probably by remodeling gut microbiota and metabolome. IMPORTANCE: Alginate has been included in traditional Chinese medicine and daily diet for centuries. Recently discovered biological activities suggested that alginate-derived alginate oligosaccharides (AOS) might be an active ingredient in traditional Chinese medicine, but how these AOS are metabolized in the gut and how it affects health need more information. The study on the working mechanism of alginate utilization loci (AUL) by the gut microorganism uncovers the role of unsaturated alginate oligosaccharides (uAOS) assimilation in tuning short-chain fatty acids and amino acids metabolism and demonstrates that uAOS metabolism by gut microorganisms results in a variation of cell metabolites, which potentially contributes to the physiology and health of gut.

Rapid hydrolysis of NO2 at High Ionic Strengths of Deliquesced Aerosol Particles.

Nitrogen dioxide (NO2) hydrolysis in deliquesced aerosol particles forms nitrous acid and nitrate and thus impacts air quality, climate, and the nitrogen cycle. Traditionally, it is considered to proceed far too slowly in the atmosphere. However, the significance of this process is highly uncertain because kinetic studies have only been made in dilute aqueous solutions but not under high ionic strength conditions of the aerosol particles. Here, we use laboratory experiments, air quality models, and field measurements to examine the effect of the ionic strength on the reaction kinetics of NO2 hydrolysis. We find that high ionic strengths (I) enhance the reaction rate constants (kI) by more than an order of magnitude compared to that at infinite dilution (kI=0), yielding log10(kI/kI=0) = 0.04I or rate enhancement factor = 100.04I. A state-of-the-art air quality model shows that the enhanced NO2 hydrolysis reduces the negative bias in the simulated concentrations of nitrous acid by 28% on average when compared to field observations over the North China Plain. Rapid NO2 hydrolysis also enhances the levels of nitrous acid in other polluted regions such as North India and further promotes atmospheric oxidation capacity. This study highlights the need to evaluate various reaction kinetics of atmospheric aerosols with high ionic strengths.