Astaxanthin attenuates cigarette smoke-induced small airway remodeling via the AKT1 signaling pathway.

BACKGROUND: Astaxanthin (AXT) is a keto-carotenoid with a variety of biological functions, including antioxidant and antifibrotic effects. Small airway remodeling is the main pathology of chronic obstructive pulmonary disease (COPD) and is caused by epithelial-to-mesenchymal transition (EMT) and fibroblast differentiation and proliferation. Effective therapies are still lacking. This study aimed to investigate the role of AXT in small airway remodeling in COPD and its underlying mechanisms. METHODS: First, the model of COPD mice was established by cigarette smoke (CS) exposure combined with intraperitoneal injection of cigarette smoke extract (CSE). The effects of AXT on the morphology of CS combined with CSE -induced emphysema, EMT, and small airway remodeling by using Hematoxylin-eosin (H&E) staining, immunohistochemical staining, and western blot. In addition, in vitro experiments, the effects of AXT on CSE induced-EMT and fibroblast function were further explored. Next, to explore the specific mechanisms underlying the protective effects of AXT in COPD, potential targets of AXT in COPD were analyzed using network pharmacology. Finally, the possible mechanism was verified through molecular docking and in vitro experiments. RESULTS: AXT alleviated pulmonary emphysema, EMT, and small airway remodeling in a CS combined with CSE -induced mouse model. In addition, AXT inhibited the EMT process in airway cells and the differentiation and proliferation of fibroblasts. Mechanistically, AXT inhibited myofibroblast activation by directly binding to and suppressing the phosphorylation of AKT1. Therefore, our results show that AXT protects against small airway remodeling by inhibiting AKT1. CONCLUSIONS: The present study identified and illustrated a new food function of AXT, indicating that AXT could be used in the therapy of COPD-induced small airway remodeling.

HDAC6-selective inhibitor CAY10603 ameliorates cigarette smoke-induced small airway remodeling by regulating epithelial barrier dysfunction and reversing.

BACKGROUND: Small airway remodelling is a vital characteristic of chronic obstructive pulmonary disease (COPD), which is mainly caused by epithelial barrier dysfunction and epithelial-mesenchymal transition (EMT). Recent studies have indicated that histone deacetylase 6 (HDAC6) plays an important role in the dysregulation of epithelial function. In this study, we investigated the therapeutic effects and underlying mechanisms of an inhibitor with high selectivity for HDAC6 in COPD. METHODS: Cigarette smoke (CS) exposure was used to establish a CS-induced COPD mouse model. CAY10603 at doses of 2.5 and 10 mg/kg was injected intraperitoneally on alternate days. The protective effects of CAY10603 against CS-induced emphysema, epithelial barrier function and small airway remodeling were evaluated using hematoxylin and eosin (H&E) staining, Masson's trichrome staining, immunohistochemical staining, and western blot. The human lung bronchial epithelial cell line (HBE) was used to elucidate the underlying molecular mechanism of action of CAY10603. RESULTS: HDAC6 levels in the lung homogenates of CS-exposed mice were higher than that those in control mice. Compared to the CS group, the mean linear intercept (MLI) of the CAY10603 treatment group decreased and the mean alveolar number (MAN)increased. Collagen deposition was reduced in groups treated with CAY10603. The expression of α-SMA was markedly upregulated in the CS group, which was reversed by CAY10603 treatment. Conversely, E-cadherin expression in the CS group was further downregulated, which was reversed by CAY10603 treatment. CAY10603 affects the tight junction protein expression of ZO-1 and occludin. ZO-1 and occludin expression were markedly downregulated in the CS group. After CAY10603treatment, the protein expression level of ZO-1 and occludin increased significantly. In HBE cells, Cigarette smoke extract (CSE) increased HDAC6 levels. CAY10603 significantly attenuated the release of TGF-ß1 induced by CSE. CAY10603 significantly increased the E-cadherin levels in TGF-ß1 treated HBE cells, while concurrently attenuated α-SMA expression. This effect was achieved through the suppression of Smad2 and Smad3 phosphorylation. CAY10603 also inhibited TGF-ß1 induced cell migration. CONCLUSIONS: These findings suggested that CAY10603 inhibited CS induced small airway remodelling by regulating epithelial barrier dysfunction and reversing EMT via the TGF-ß1/Smad2/3 signalling pathway.

Efficacy of high-flow nasal cannula in patients with acute heart failure: a systematic review and meta-analysis.

BACKGROUND: Acute heart failure (AHF) is often associated with diffuse insufficiency and arterial hypoxemia, requiring respiratory support for rapid and effective correction. We aimed to compare the effects of high-flow nasal cannula(HFNC) with those of conventional oxygen therapy(COT) or non-invasive ventilation(NIV) on the prognosis of patients with AHF. METHODS: We performed the search using PubMed, Embase, Web of Science, MEDLINE, the Cochrane Library, CNKI, Wanfang, and VIP databases from the inception to August 31, 2023 for relevant studies in English and Chinese. We included controlled studies comparing HFNC with COT or NIV in patients with AHF. Primary outcomes included the intubation rate, respiratory rate (RR), heart rate (HR), and oxygenation status. RESULTS: From the 1288 original papers identified, 16 studies met the inclusion criteria, and 1333 patients were included. Compared with COT, HFNC reduced the intubation rate (odds ratio [OR]: 0.29, 95% CI: 0.14-0.58, P = 0.0005), RR (standardized mean difference [SMD]: -0.73 95% CI: -0.99 - -0.47, P < 0.00001) and HR (SMD: -0.88, 95% CI: -1.07 - -0.69, P < 0.00001), and hospital stay (SMD: -0.94, 95% CI: -1.76 - -0.12, P = 0.03), and increase arterial oxygen partial pressure (PaO2), (SMD: 0.88, 95% CI: 0.70-1.06, P < 0.00001) and oxygen saturation (SpO2 [%], SMD: 0.70, 95% CI: 0.34-1.06, P = 0.0001). CONCLUSIONS: There were no significant differences in intubation rate, RR, HR, arterial blood gas parameters, and dyspnea scores between the HFNC and NIV groups. Compared with COT, HFNC effectively reduced the intubation rate and provided greater clinical benefits to patients with AHF. However, there was no significant difference in the clinical prognosis of patients with AHF between the HFNC and NIV groups. TRIAL REGISTRATION: PROSPERO (identifier: CRD42022365611).

Rice-produced classical swine fever virus glycoprotein E2 with herringbone-dimer design to enhance immune responses.

Pestiviruses, including classical swine fever virus, remain a concern for global animal health and are responsible for major economic losses of livestock worldwide. Despite high levels of vaccination, currently available commercial vaccines are limited by safety concerns, moderate efficacy, and required high doses. The development of new vaccines is therefore essential. Vaccine efforts should focus on optimizing antigen presentation to enhance immune responses. Here, we describe a simple herringbone-dimer strategy for efficient vaccine design, using the classical swine fever virus E2 expressed in a rice endosperm as an example. The expression of rE2 protein was identified, with the rE2 antigen accumulating to 480 mg/kg. Immunological assays in mice, rabbits, and pigs showed high antigenicity of rE2. Two immunizations with 284 ng of the rE2 vaccine or one shot with 5.12 µg provided effective protection in pigs without interference from pre-existing antibodies. Crystal structure and small-angle X-ray scattering results confirmed the stable herringbone dimeric conformation, which had two fully exposed duplex receptor binding domains. Our results demonstrated that rice endosperm is a promising platform for precise vaccine design, and this strategy can be universally applied to other Flaviviridae virus vaccines.

Point-of-care ultrasound-guided submucosal paclitaxel injection in tracheal stenosis model.

Background and Objectives: Transcutaneous point-of-care ultrasound (POCUS) is a good tool to monitor the trachea in many clinical practices. The aim of our study is to verify the feasibility of POCUS-guided submucosal injection as a potential drug delivery method for the treatment of tracheal stenosis. Materials and methods: The inner wall of the trachea was monitored via a bronchoscope during the POCUS-guided submucosal injection of methylene blue in fresh ex vivo porcine trachea to evaluate the distribution of methylene blue. The feasibility and eficacy of POCUS-guided submucosal injection were evaluated in a tracheal stenosis rabbit model. Animals were divided into sham group, tracheal stenosis group, and treatment group. Ten days after the scraping of the tracheal mucosa or sham operation, POCUS-guided submucosal injection of paclitaxel or saline was performed. Seven days after the submucosal injection, the trachea was assessed by cervical computed tomography (CT) scan and ultrasound. Results: The distribution of methylene blue in trachea proved the technical feasibility of POCUS-guided submucosal injection. CT evaluation revealed that the tracheal stenosis index and the degree of tracheal stenosis increased significantly in the stenosis group, while POCUS-guided submucosal injection of paclitaxel partially reversed the tracheal stenosis. POCUS-guided submucosal injection of paclitaxel also decreased the lamina propria thickness and collagen deposition in the stenosed trachea. Conclusion: POCUS-guided submucosal paclitaxel injection alleviated tracheal stenosis induced by scraping of the tracheal mucosa. POCUS-guided submucosal injection might be a potential method for the treatment of tracheal stenosis.

The various effect of cow manure compost on the degradation of imazethapyr in different soil types.

Adding compost to soil is an effective strategy to promote the degradation of organic pollutants and reduce ecological risks. However, the effect of compost on the degradation of imazethapyr (IMET) in different soil types is not clear. To address this issue, a pot experiment was conducted, and high-throughput sequencing and mass spectrometry technology were used to identify the influence of cow manure compost on the degradation efficiency of IMET in black soil and saline-alkali soil and the role of key microorganisms. The results showed that adding compost to black soil increased the degradation rate of IMET by 12.58% and shortened the half-life by 53.37%, while in saline-alkali soil, the degradation rate of IMET decreased by 6.99% with no significant change in the half-life. High-throughput sequencing results showed that adding cow manure compost (mass ratio of 4%) significantly increased the abundance of bacterial families capable of degrading organic pollutants in black soil, but had an inhibitory effect on this bacterial community in saline-alkali soil. Redundancy analysis (RDA) results showed that total organic carbon (TOC), alkali-hydrolyzable nitrogen (AN), ammonia nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) were the main factors driving microbial community variation. Mass spectrometry analysis indicated that IMET generated three metabolites during the degradation process. Sphingomonadaceae and Vicinamibacteraceae could accelerate the breaking of side-chain alkyl groups, while Chitinophagaceae could cause the rearrangement of the imidazole ring structure, gradually metabolizing IMET into small organic molecules. The application of appropriate cow manure compost can promote the development of IMET-degrading bacteria by adjusting the organic carbon and dissolved nitrogen content in black soil. In the future, the quantitative effects of organic fertilizer application on the IMET degradation process in different soil types should be further analyzed, and microbial isolation and purification should be used to enhance the ability of microorganisms to degrade herbicides.

Glycyl-l-histidyl-l-lysine-Cu2+ rescues cigarette smoking-induced skeletal muscle dysfunction via a sirtuin 1-dependent pathway.

BACKGROUND: Skeletal muscle dysfunction is an important co-morbidity in patients with chronic obstructive pulmonary disease (COPD) and is significantly associated with increased mortality. Oxidative stress has been demonstrated an important trigger for COPD-related skeletal muscle dysfunction. Glycine-histidine-lysine (GHK) is an active tripeptide, which is a normal component of human plasma, saliva, and urine; promotes tissue regeneration; and acts as an anti-inflammatory and antioxidant properties. The purpose of this study was to determine whether GHK is involved in COPD-related skeletal muscle dysfunction. METHODS: The plasma GHK level in patients with COPD (n = 9) and age-paired healthy subjects (n = 11) were detected using reversed-phase high-performance liquid chromatography. The complex GHK with Cu (GHK-Cu) was used in in vitro (C2C12 myotubes) and in vivo experiments (cigarette smoking [CS]-exposure mouse model) to explore the involvement of GHK in CS-induced skeletal muscle dysfunction. RESULTS: Compared with healthy control, plasma GHK levels were decreased in patients with COPD (70.27 ± 38.87 ng/mL vs. 133.0 ± 54.54 ng/mL, P = 0.009). And plasma GHK levels in patients with COPD were associated with pectoralis muscle area (R = 0.684, P = 0.042), inflammatory factor TNF-α (R = -0.696, P = 0.037), and antioxidative stress factor SOD2 (R = 0.721, P = 0.029). GHK-Cu was found to rescue CSE-induced skeletal muscle dysfunction in C2C12 myotubes, as evidenced by increased expression of myosin heavy chain, reduced expression of MuRF1 and atrogin-1, elevated mitochondrial content, and enhanced resistance to oxidative stress. In CS-induced muscle dysfunction C57BL/6 mice, GHK-Cu treatment (0.2 and 2 mg/kg) reduces CS-induced muscle mass loss (skeletal muscle weight (1.19 ± 0.09% vs. 1.29 ± 0.06%, 1.40 ± 0.05%; P < 0.05) and muscle cross-sectional area elevated (1055 ± 552.4 µm2 vs. 1797 ± 620.9 µm2 , 2252 ± 534.0 µm2 ; P < 0.001), and also rescues CS-induced muscle weakness, indicated by improved grip strength (175.5 ± 36.15 g vs. 257.6 ± 37.98 g, 339.1 ± 72.22 g; P < 0.01). Mechanistically, GHK-Cu directly binds and activates SIRT1(the binding energy was -6.1 kcal/mol). Through activating SIRT1 deacetylation, GHK-Cu inhibits FoxO3a transcriptional activity to reduce protein degradation, deacetylates Nrf2 and contribute to its action of reducing oxidative stress by generation of anti-oxidant enzymes, increases PGC-1α expression to promote mitochondrial function. Finally, GHK-Cu could protect mice against CS-induced skeletal muscle dysfunction via SIRT1. CONCLUSIONS: Plasma glycyl-l-histidyl-l-lysine level in patients with chronic obstructive pulmonary disease was significantly decreased and was significantly associated with skeletal muscle mass. Exogenous administration of glycyl-l-histidyl-l-lysine-Cu2+ could protect against cigarette smoking-induced skeletal muscle dysfunction via sirtuin 1.

Spatial and temporal regulation of homogeneous nucleation and crystal growth for high-flux electrochemical water softening.

Electrochemical softening is an effective technology for the treatment of circulating cooling water, but its hardness removal efficiency is limited because that nucleation and growth of scale crystals depended on cathode surface. In this study, a novel method was proposed to break through this limit via spatiotemporal management of nucleation and growth processes. A cube reactor was divided into cathodic chamber and anodic chamber via installing a sandwich structure module composed of mesh cathode, nylon nets, and mesh anode. Using this continuous-flowing electrochemical reactor, OH ̄ generated by water electrolysis was rapidly pushed away from cathode surface by water flow and hydrogen bubbles movement. As a result, a wide range of strongly alkaline regions was rapidly constructed in cathodic chamber to play a nucleation region, and homogeneous nucleation in liquid phase replaced heterogeneous nucleation on cathodic surface. Furthermore, the growth process of scale crystals in alkaline regions was monitored in situ. It took only 150 s of residence time to grow to 500 nm, which may be easily separated from water by a microfiltration membrane. With this new method, the precipitation rate was 290.8 g/(hˑm2) and corresponding energy consumption was 2.1 kW·h/kg CaCO3, both were superior to those reported values. Therefore, this study developed an efficient electrochemical softening method by spatial and temporal regulation of homogeneous nucleation and crystal growth processes.

Ultrasound Assessment of the Rectus Femoris in Patients with Chronic Obstructive Pulmonary Disease Predicts Sarcopenia.

Purpose: Sarcopenia, an age-related loss of skeletal muscle mass and function, is frequent in patients with chronic obstructive pulmonary disease (COPD) and is linked to a poor prognosis. The diagnosis of sarcopenia requires specific equipment and is inconvenient to introduce into clinical practice. Ultrasound is an innovative method to assess muscle quantity. The objective of this research was to evaluate the use of ultrasound for prospectively screening for sarcopenia in COPD patients. Patients and Methods: A total of 235 stable patients with COPD were included in this observational study and divided into development and validation sets. The Asian Working Group for Sarcopenia standards were used to define sarcopenia. The thickness (RFthick) and cross-sectional area (RFcsa) of the rectus femoris were measured using ultrasound. Receiver operating characteristic curve analysis of RFthick and RFcsa was used to predict sarcopenia. Nomogram models were constructed based on RFthick, RFcsa, age and body mass index to identify sarcopenia. Results: Sarcopenia was present in 83 (35.32%) patients. Patients with sarcopenia had advanced age, decreased pulmonary function, decreased physical function and poor clinical outcomes. RFthick and RFcsa showed good predictive ability for sarcopenia in the development and validation sets. The nomogram based on RFthick and RFcsa could detect sarcopenia in COPD patients, and all had significant predictive performance in the development and validation sets. The calibration plot showed good agreement between the nomogram predictions and actual observations. Conclusion: The ultrasound measurement of the rectus femoris has potential for the clinical assessment of sarcopenia in patients with COPD.

A mechanism for SARS-CoV-2 RNA capping and its inhibition by nucleotide analog inhibitors.

Decoration of cap on viral RNA plays essential roles in SARS-CoV-2 proliferation. Here, we report a mechanism for SARS-CoV-2 RNA capping and document structural details at atomic resolution. The NiRAN domain in polymerase catalyzes the covalent link of RNA 5' end to the first residue of nsp9 (termed as RNAylation), thus being an intermediate to form cap core (GpppA) with GTP catalyzed again by NiRAN. We also reveal that triphosphorylated nucleotide analog inhibitors can be bonded to nsp9 and fit into a previously unknown "Nuc-pocket" in NiRAN, thus inhibiting nsp9 RNAylation and formation of GpppA. S-loop (residues 50-KTN-52) in NiRAN presents a remarkable conformational shift observed in RTC bound with sofosbuvir monophosphate, reasoning an "induce-and-lock" mechanism to design inhibitors. These findings not only improve the understanding of SARS-CoV-2 RNA capping and the mode of action of NAIs but also provide a strategy to design antiviral drugs.

The root-specific NtR12 promoter-based expression of RIP increased the resistance against bacterial wilt disease in tobacco.

BACKGROUND: Tobacco is an important economic crop, but the quality and yield have been severely impaired by bacterial wilt disease (BWD) caused by Ralstonia solanacearum. METHODS AND RESULTS: Here, we describe a transgenic approach to prevent BWD in tobacco plants. A new root-specific promoter of an NtR12 gene was successfully cloned. The NtR12 promoter drove GUS reporter gene expression to a high level in roots but to less extent in stems, and no significant expression was detected in leaves. The Ribosome-inactivating proteins (RIP) gene from Momordica charantia was also cloned, and its ability to inhibit Ralstonia solanacearum was evaluated using RIP protein produced by the prokaryotic expression system. The RIP gene was constructed downstream of the NtR12 promoter and transformed into the tobacco cultivar "Cuibi No. 1" (CB-1), resulting in many descendants. The resistance against BWD was significantly improved in transgenic tobacco lines expressing NtR12::RIP. CONCLUSION: This study confirms that the RIP gene confers resistance to BWD and the NtR12 as a new promoter for its specific expression in root and stem. Our findings pave a novel avenue for transgenic engineering to prevent the harmful impact of diseases and pests in roots and stems.

Glycyl-L-histidyl-L-lysine-Cu2+ attenuates cigarette smoke-induced pulmonary emphysema and inflammation by reducing oxidative stress pathway.

Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder manifested as chronic airway inflammation and persistent airflow limitation with the essential mechanism as inflammatory response and oxidative stress induced by toxic exposures such as cigarette smoke (CS). Glycyl-L-histidyl-L-lysine (GHK) is a nontoxic tripeptide involved in the process of healing and regeneration as a natural product. With the combination of Cu(II), glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) improves antioxidative and anti-inflammatory bioavailability, and they might offer potential therapeutic properties for COPD. Thus, the present study aimed to identify the potential effects of GHK-Cu on emphysema induced by cigarette smoke. Methods: In the in vivo experiment, C57BL/6J mice were exposed to CS for 12 weeks to induce pulmonary emphysema. GHK-Cu was injected intraperitoneally at doses of 0.2, 2 and 20 µg/g/day in 100 µl of saline on alternative days from the 1st day after CS exposure. The effects of GHK-Cu on the morphology of CS-induced emphysema, the inflammatory response and oxidative stress were evaluated. The antioxidative effect of GHK-Cu on human alveolar epithelial A549 cells was assessed in vitro. Results: GHK-Cu treatment attenuated the CS-induced emphysematous changes and partially reversed the matrix metalloprotein -9 (MMP-9)/tissue inhibitor of metalloproteinases-1 (TIMP-1) imbalance in the lung tissue. GHK-Cu reduced the inflammation and oxidation by decreasing the expression of inflammatory cytokines (IL-1ß and TNF-α) in the bronchoalveolar lavage and the enzymatic activity of MPO and MDA in the lung homogenate while restoring the T-AOC and GSH content. Furthermore, administration of GHK-Cu reversed the increase in NF-κB expression induced by CS and increased the Nrf2 level, as an antioxidant defense component, in mice with chronic CS exposure. In CSE-exposed human alveolar epithelial A549 cells, GHK-Cu also inhibited oxidative stress by suppressing MDA levels and restoring T-AOC and GSH levels, which were modulated by upregulating Nrf2 expression. Conclusion: GHK-Cu treatment attenuated CS-induced emphysema by anti-inflammation by downregulating NF-κB and antioxidation via upregulation of the Nrf2/Keap1 in lung tissues.

Plant photosynthetic overcompensation under nocturnal warming: lack of evidence in subtropical evergreen trees.

BACKGROUND AND AIMS: Increased plant photosynthesis under nocturnal warming is a negative feedback mechanism to overcompensate for night-time carbon loss to mitigate climate warming. This photosynthetic overcompensation effect has been observed in dry deciduous ecosystems but whether it exists in subtropical wet forest trees is unclear. METHODS: Two subtropical evergreen tree species (Schima superba and Castanopsis sclerophylla) were grown in a greenhouse and exposed to ambient and elevated night-time temperature. The occurrence of the photosynthetic overcompensation effect was determined by measuring daytime and night-time leaf gas exchange and non-structural carbohydrate (NSC) concentration. KEY RESULTS: A reduction in leaf photosynthesis for both species and an absence of persistent photosynthetic overcompensation were observed. The photosynthetic overcompensation effect was transient in S. superba due to respiratory acclimation and stomatal limitation. For S. superba, nocturnal warming resulted in insufficient changes in night-time respiration and NSC concentration to stimulate overcompensation and inhibited leaf stomatal conductance by increasing the leaf-to-air vapour pressure deficit. CONCLUSIONS: The results indicate that leaf stomatal conductance is important for the photosynthetic overcompensation effect in different tree species. The photosynthetic overcompensation effect under nocturnal warming may be a transient occurrence rather than a persistent mechanism in subtropical forest ecosystems.

Value of endorectal ultrasonography in the assessment of invasion staging of low rectal cancer with local progression after neoadjuvant radiochemotherapy / Valor de la ultrasonografía endorectal en la evaluación de la estadificación de la invasión del cáncer rectal bajo con progresión local, después de administrar radioquimioterapia neoadyuvante

Abstract Although stages T3 and T4 rectal cancer can be reduced to T1 or T2 after neoadjuvant radiochemotherapy, the accuracy of the endorectal ultrasonography (ERUS) for the post-radiochemotherapy evaluation of low rectal cancer has seldom been reported. We aimed to investigate the value of ERUS in the assessment of invasion staging in low rectal cancer with local progression, and the factors affecting its accuracy, after neoadjuvant radiochemotherapy. A total of 114 patients administered with neoadjuvant radiochemotherapy for stages II and III low rectal cancer (local stage T3/T4) from February 2018 to December 2020 were enrolled in the study. The changes in local lesions were evaluated using ERUS before and after radiochemotherapy, and compared with the pathological T staging. The accuracy of post-neoadjuvant radiochemotherapy re-staging examined with ERUS was evaluated, and univariate analysis was used to identify the factors affecting the accuracy. After neoadjuvant radiochemotherapy, the blood flow distribution within the lesion significantly declined (P<0.05), the max length and max thickness of the longitudinal axis of the lesion were reduced (P<0.05), and the uT staging was decreased (P<0.05), when compared with lesions before the treatment. Compared with postoperative pathological T staging, the accuracies of ERUS in T1, T2, T3 and T4 stages were 11.11%, 28.57%, 27.27% and 100%, respectively. Univariate analysis indicated that review time of ERUS, post-operative T staging and Wheeler rectal regression stage were factors affecting the accuracy of ERUS re-staging. ERUS is more accurate for T4 re-staging, follow-up reviewed six weeks after neoadjuvant radiochemotherapy and low regression tumors, with a high application value for the assessment of the efficacy of neoadjuvant radiochemotherapy for low rectal cancer.

Resumen Aunque el cáncer de recto en estadios T3 y T4 se puede reducir a T1 o T2 después de la radioquimioterapia neoadyuvante, rara vez se ha informado la precisión de la ecografía endorrectal (ERUS) para la evaluación posterior a la radioquimioterapia del cáncer de recto inferior. Nuestro objetivo fue investigar el valor de ERUS en la evaluación de la estadificación de la invasión en el cáncer de recto inferior con progresión local, después de la radioquimioterapia neoadyuvante y los factores que afectan su precisión. Se incluyeron en el estudio un total de 114 pacientes a los que se les administró radioquimioterapia neoadyuvante para el cáncer de recto inferior en estadios II y III (estadio local T3/T4), desde febrero de 2018 hasta diciembre de 2020. Los cambios en las lesiones locales se evaluaron mediante ERUS antes y después de la radioquimioterapia y se compararon con la estadificación patológica T. Se evaluó la precisión de la re-estadificación examinada con ERUS, después de la radioquimioterapia neoadyuvante y se utilizó un análisis univariado para identificar los factores que afectan su precisión. Después de la radioquimioterapia neoadyuvante, la distribución del flujo sanguíneo dentro de la lesión disminuyó significativamente (P<0,05), la longitud máxima y el espesor máximo del eje longitudinal de la lesión se redujeron (P<0,05) y la estadificación uT disminuyó (P<0,05), en comparación con las lesiones antes del tratamiento. En comparación con la estadificación T patológica posoperatoria, las precisiones de ERUS en las etapas T1, T2, T3 y T4 fueron del 11,11%, 28,57%, 27,27% y 100%, respectivamente. El análisis univariable indicó que el tiempo de revisión de ERUS, la estadificación T postoperatoria y la etapa de regresión rectal de Wheeler fueron factores que afectaron la precisión de la re-estadificación con ERUS. ERUS es más preciso para la re-estadificación de T4, el seguimiento seis semanas después de la radioquimioterapia neoadyuvante y en tumores de baja regresión, con un alto valor de aplicación para la evaluación de la eficacia de la radioquimioterapia neoadyuvante para el cáncer rectal bajo.

Experimental warming reduces ecosystem resistance and resilience to severe flooding in a wetland.

Climate warming and extreme hydrological events are threatening the sustainability of wetlands across the globe. However, whether climate warming will amplify or diminish the impact of extreme flooding on wetland ecosystems is unknown. Here, we show that climate warming significantly reduced wetland resistance and resilience to a severe flooding event via a 6-year warming experiment. We first found that warming rapidly altered plant community structure by increasing the dominance of low-canopy species. Then, we showed that warming reduced the resistance and resilience of vegetation productivity to a 72-cm flooding event. Last, we detected slower postflooding carbon processes, such as gross ecosystem productivity, soil respiration, and soil methane emission, under the warming treatment. Our results demonstrate how severe flooding can destabilize wetland vegetation structure and ecosystem function under climate warming. These findings indicate an enhanced footprint of extreme hydrological events in wetland ecosystems in a warmer climate.

Nocturnal warming accelerates drought-induced seedling mortality of two evergreen tree species.

Extreme drought is one of the key climatic drivers of tree mortality on a global scale. However, it remains unclear whether the drought-induced tree mortality will increase under nocturnal climate warming. Here we exposed seedlings of two wide-ranging subtropical tree species, Castanopsis sclerophylla and Schima superba, with contrasting stomatal regulation strategies to prolonged drought under ambient and elevated night-time temperature by 2 °C. We quantified the seedling survival time since drought treatment by measuring multiple leaf traits such as leaf gas exchange, predawn leaf water potential and water-use efficiency. The results showed that all seedlings in the ambient temperature died within 180 days and 167 days of drought for C. sclerophylla and S. superba, respectively. Night warming significantly shortened the survival time of C. sclerophylla, by 31 days, and S. superba by 28 days, under the drought treatment. A survival analysis further showed that seedlings under night warming suffered a 1.6 times greater mortality risk than those under ambient temperature. Further analyses revealed that night warming suppressed net leaf carbon gain in both species by increasing the nocturnal respiratory rate of S. superba across the first 120 days of drought and decreasing the photosynthetic rate of both species generally after 46 days of drought. These effects on net carbon gain were more pronounced in S. superba than C. sclerophylla. After 60 days of drought, night warming decreased the predawn leaf water potential and leaf water-use efficiency of C. sclerophylla but not S. superba. These contrasting responses are partially due to variations in stomatal control between the two species. These findings suggest that stomatal traits can regulate the response of leaf gas exchange and plant water-use to nocturnal warming during drought. This study indicates that nocturnal warming can accelerate tree mortality during drought. Night warming accelerates the mortality of two subtropical seedlings under drought.Night warming differently affects the drought response of leaf gas exchange and plant water-use between the two species due to species-specific stomatal morphological traits.Carbon metabolism changes and hydraulic damage play differential roles in driving night-warming impacts on the drought-induced mortality between the two species.

A viral protein disrupts vacuolar acidification to facilitate virus infection in plants.

Vacuolar acidification is essential for vacuoles in diverse physiological functions. However, its role in plant defense, and whether and how pathogens affect vacuolar acidification to promote infection remain unknown. Here, we show that Barley stripe mosaic virus (BSMV) replicase γa, but not its mutant γaR569A , directly blocks acidification of vacuolar lumen and suppresses autophagic degradation to promote viral infection in plants. These were achieved via molecular interaction between γa and V-ATPase catalytic subunit B2 (VHA-B2), leading to disruption of the interaction between VHA-B2 and V-ATPase catalytic subunit E (VHA-E), which impairs the membrane localization of VHA-B2 and suppresses V-ATPase activity. Furthermore, a mutant virus BSMVR569A with the R569A point mutation possesses less viral pathogenicity. Interestingly, multiple viral infections block vacuolar acidification. These findings reveal that functional vacuolar acidification is required for plant antiviral defense and disruption of vacuolar acidification could be a general viral counter-defense strategy employed by multiple viruses.

Effectiveness of Telemonitoring for Reducing Exacerbation Occurrence in COPD Patients With Past Exacerbation History: A Systematic Review and Meta-Analysis.

Background: Although an increasing number of studies have reported that telemonitoring (TM) in patients with chronic obstructive pulmonary disease (COPD) can be useful and efficacious for hospitalizations and quality of life, its actual utility in detecting and managing acute exacerbation of COPD (AECOPD) is less established. This meta-analysis aimed to identify the best available evidence on the effectiveness of TM targeting the early and optimized management of AECOPD in patients with a history of past AECOPD compared with a control group without TM intervention. Methods: We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials published from 1990 to May 2020. Primary endpoints included emergency room visits and exacerbation-related readmissions. P-values, risk ratios, odds ratios, and mean differences with 95% confidence intervals were calculated. Results: Of 505 identified citations, 17 original articles with both TM intervention and a control group were selected for the final analysis (N = 3,001 participants). TM was found to reduce emergency room visits [mean difference (MD) -0.70, 95% confidence interval (CI) -1.36 to -0.03], exacerbation-related readmissions (risk ratio 0.74, 95% CI 0.60-0.92), exacerbation-related hospital days (MD -0.60, 95% CI -1.06 to -0.13), mortality (odds ratio 0.71, 95% CI 0.54-0.93), and the St. George's Respiratory Questionnaire (SGRQ) score (MD -3.72, 95% CI -7.18 to -0.26) but did not make a difference with respect to all-cause readmissions, the rate of exacerbation-related readmissions, all-cause hospital days, time to first hospital readmission, anxiety and depression, and exercise capacity. Furthermore, the subgroup analysis by observation period showed that longer TM (≥12 months) was more effective in reducing readmissions. Conclusions: TM can reduce emergency room visits and exacerbation-related readmissions, as well as acute exacerbation (AE)-related hospital days, mortality, and the SGRQ score. The implementation of TM intervention is thus a potential protective therapeutic strategy that could facilitate the long-term management of AECOPD. Systematic Review Registration: This systematic review and meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement and was registered at International Prospective Register of Systematic Reviews (number: CRD42020181459).

Application value of conventional ultrasound combined with shear wave elastography in diagnosing triple negative breast cancer.

BACKGROUND: At present, most ultrasound (US) studies on triple negative breast cancer (TNBC) are limited to conventional US features, so it is necessary to develop new joint diagnostic methods. The study aims to explore the values of conventional US and shear wave elastography (SWE) in differential diagnoses of TNBC and non-TNBC. METHODS: A total of 120 breast cancer (BC) patients involving 120 lesions that were pathologically verified were retrospectively analyzed in this study. All participants had received both conventional US and SWE before surgery. Meanwhile, the participants were divided into a TNBC group or a non-TNBC group according to their immunohistochemical (IHC) results. The differences between the conventional US features (including lesion shape, growth location, margin, boundary, internal echo, micro-calcification, posterior echo, and internal blood supply) and the SWE image features [including mean lesion hardness (Emean), maximum (Emax), minimum (Emin), standard deviation (SD), and ratio to normal gland (Eratio)] of 2 groups were compared. The receiver operating characteristic (ROC) curve of the diagnosed lesion was calculated by the area under the curve (AUC). RESULTS: According to the findings of conventional US, the TNBC group mostly manifested as a micro-lobulated margin, with a clear boundary and no internal micro-calcification; the non-TNBC group mainly manifested as marginal angulation or burr, and hyper-echo halo in the boundary, accompanied with internal micro-calcification, and the difference was statistically significant (P<0.05); the internal thrombolysis in myocardial infarction (TIMI) and resistance index between the TNBC group and non-TNBC group were similar, and the differences were not statistically significant (P>0.05). The findings of SWE were as follows: differences in Emax, Emean, and Eratio values between 2 groups were statistically significant (P<0.05); and the areas under the ROC curve (AUC) of these three in diagnosing the lesions were 0.811, 0.781 and 0.770, respectively. CONCLUSIONS: Conventional US combined with SWE can comprehensively analyze the morphological, blood supply, and hardness features of breast lesions, and provide more reliable information for the differential diagnosis between TNBC and non-TNBC.