Partial root-zone drying irrigation improves intrinsic water-use efficiency and maintains high photosynthesis by uncoupling stomatal and mesophyll conductance in cotton leaves.

Partial root-zone drying irrigation (PRD) can improve water-use efficiency (WUE) without reductions in photosynthesis; however, the mechanism by which this is attained is unclear. To amend that, PRD conditions were simulated by polyethylene glycol 6000 in a root-splitting system and the effects of PRD on cotton growth were studied. Results showed that PRD decreased stomatal conductance (gs) but increased mesophyll conductance (gm). Due to the contrasting effects on gs and gm, net photosynthetic rate (AN) remained unaffected, while the enhanced gm/gs ratio facilitated a larger intrinsic WUE. Further analyses indicated that PRD-induced reduction of gs was related to decreased stomatal size and stomatal pore area in adaxial and abaxial surface which was ascribed to lower pore length and width. PRD-induced variation of gm was ascribed to the reduced liquid-phase resistance, due to increases in chloroplast area facing to intercellular airspaces and the ratio of chloroplast surface area to total mesophyll cell area exposed to intercellular airspaces, as well as to decreases in the distance between cell wall and chloroplast, and between adjacent chloroplasts. The above results demonstrate that PRD, through alterations to stomatal and mesophyll structures, decoupled gs and gm responses, which ultimately increased intrinsic WUE and maintained AN.

Changes in carbohydrate distribution in cotton photosynthetic organs and increase in boll weight reduce yield loss under high temperature.

Yield of cotton (Gossypium hirsutum) does not always fall with high temperature (HT) even though this induces significant reductions in fruit retention. To investigate the underlying mechanisms, a greenhouse experiment was conducted with two temperature regimes [control treatment, 28 °C; high temperature (HT), 34 °C] for 7 d. Results showed HT did not significantly influence cotton yield, but reduced boll number and increased boll weight. The 13C distribution ratio of the leaf subtending the cotton boll (LSCB) decreased while that of the cotton boll increased under HT. Transcriptomic and proteomic analyses of the LSCB revealed up-regulated genes involved in cytokinin and jasmonic acid synthesis, as well as SWEET15 (GH_D01G0218), which positively regulated photosynthesis and transport photosynthate, ultimately leading to increased boll weight. After 7 d recovery from HT, the 13C distribution ratio of the LSCB increased while that of the cotton boll decreased. However, boll weight still increased, which was related to increased amylase and sucrose phosphate synthase activities and up-regulated sucrose transport genes in the main-stem leaf and capsule wall. Thus, both accelerated sucrose synthesis and transport in the LSCB under HT and increased sucrose supply ability of the main-stem leaf and capsule wall after recovery from HT contributed to an increased boll weight, which finally maintained cotton yield.

Drought decreases cotton fiber strength by altering sucrose flow route.

The potential mechanisms by which drought restricts cotton fiber cell wall synthesis and fiber strength are still not fully understood. Herein, drought experiments were conducted using two cultivars of upland cotton (Gossypium hirsutum), Dexiamian 1 (drought-tolerant) and Yuzaomian 9110 (drought-sensitive). Results showed that drought notably reduced sucrose efflux from cottonseed coats to fibers by down-regulating the expression of GhSWEET10 and GhSWEET15 in outer cottonseed coats, leading to enhanced sucrose accumulation in cottonseed coats but decreased sucrose accumulation in fibers. Within cotton fibers, drought restricted the hydrolysis of sucrose to uridine-5'-diphosphoglucose by suppressing sucrose synthase activity, and drought favored the conversion of uridine-5'-diphosphoglucose to ß-1,3-glucan rather than cellulose by up-regulating GhCALS5. Hence, cellulose content was reduced, which was the main reason for the decreased fiber strength under drought. Moreover, drought promoted lignin synthesis by up-regulating the expression of Gh4CL4, GhPAL9, GhCCR5, GhCAD11, and GhCOMT6, which partly offset the negative influence of reduced cellulose content on fiber strength. Compared with Yuzaomian 9110, the drought-tolerance of Dexiamian 1 was evidenced by the following under drought conditions: (i) greater sucrose flow from seedcoat to fiber, (ii) less ß-1,3-glucan accumulation, and (iii) more lignin biosynthesis. Overall, this study provides new insights into the mechanism of reduced cotton fiber strength induced by drought.

Effectiveness and safety of azvudine in older adults with mild and moderate COVID-19: a retrospective observational study.

BACKGROUND: Azvudine has clinical benefits and acceptable safety against COVID-19, including in patients with comorbidities, but there is a lack of available data for its use in older adult patients. This study explored the effectiveness and safety of azvudine in older adults with mild or moderate COVID-19. METHODS: This retrospective cohort study included patients aged ≥80 diagnosed with COVID-19 at the Central Hospital of Shaoyang between October and November 2022. According to the therapies they received, the eligible patients were divided into the azvudine, nirmatrelvir/ritonavir, and standard-of-care (SOC) groups. The outcomes were the proportion of patients progressing to severe COVID-19, time to nucleic acid negative conversion (NANC), and the 5-, 7-, 10-, and 14-day NANC rates from admission. RESULTS: The study included 55 patients treated with azvudine (n = 14), nirmatrelvir/ritonavir (n = 18), and SOC (n = 23). The median time from symptom onset to NANC of the azvudine, nirmatrelvir/ritonavir, and SOC groups was 14 (range, 6-25), 15 (range, 11-24), and 19 (range, 18-23) days, respectively. The median time from treatment initiation to NANC of the azvudine and nirmatrelvir/ritonavir groups was 8 (range, 4-20) and 9 (range, 5-16) days, respectively. The median length of hospital stay in the three groups was 10.5 (range, 5-23), 13.5 (range, 10-21), and 17 (range, 10-23) days, respectively. No treatment-related adverse events or serious adverse events were reported. CONCLUSION: Azvudine showed satisfactory effectiveness and acceptable safety in older adults with mild or moderate COVID-19. Therefore, azvudine could be a treatment option for this special patient population.

Assessing the Influence of B-US, CDFI, SE, and Patient Age on Predicting Molecular Subtypes in Breast Lesions Using Deep Learning Algorithms.

OBJECTIVES: Our study aims to investigate the impact of B-mode ultrasound (B-US) imaging, color Doppler flow imaging (CDFI), strain elastography (SE), and patient age on the prediction of molecular subtypes in breast lesions. METHODS: Totally 2272 multimodal ultrasound imaging was collected from 198 patients. The ResNet-18 network was employed to predict four molecular subtypes from B-US imaging, CDFI, and SE of patients with different ages. All the images were split into training and testing datasets by the ratio of 80%:20%. The predictive performance on testing dataset was evaluated through 5 metrics including mean accuracy, precision, recall, F1-scores, and confusion matrix. RESULTS: Based on B-US imaging, the test mean accuracy is 74.50%, the precision is 74.84%, the recall is 72.48%, and the F1-scores is 0.73. By combining B-US imaging with CDFI, the results were increased to 85.41%, 85.03%, 85.05%, and 0.84, respectively. With the integration of B-US imaging and SE, the results were changed to 75.64%, 74.69%, 73.86%, and 0.74, respectively. Using images from patients under 40 years old, the results were 90.48%, 90.88%, 88.47%, and 0.89. When images from patients who are above 40 years old, they were changed to 81.96%, 83.12%, 80.5%, and 0.81, respectively. CONCLUSION: Multimodal ultrasound imaging can be used to accurately predict the molecular subtypes of breast lesions. In addition to B-US imaging, CDFI rather than SE contribute further to improve predictive performance. The predictive performance is notably better for patients under 40 years old compared with those who are 40 years old and above.

Reactive Oxygen Species Modulate Th17/Treg Balance in Chlamydia psittaci Pneumonia via NLRP3/IL-1ß/Caspase-1 Pathway Differentiation.

Chlamydia psittaci pneumonia (CPP) is a lung disease caused by the infection with the Chla-mydia psittaci bacterium, which can lead to severe acute respiratory distress syndrome and systemic symptoms. This study explored the specific mechanisms underlying the impact of reactive oxygen species (ROS) on the Th17/Treg balance in CPP. The levels of ROS and the differentiation ratio of Th17/Treg in the peripheral blood of healthy individuals and CPP patients were measured using ELISA and flow cytometry, respectively. The association between the ROS levels and Th17/Treg was assessed using Pearson correlation analysis. The ROS levels and the Th17/Treg ratio were measured in CD4+ T cells following H2O2 treatment and NLRP3 inhibition. The effects of H2O2 treatment and NLRP3 inhibition on the NLRP3/IL-1ß/caspase-1 pathway were observed using immunoblotting. Compared to the healthy group, the CPP group exhibited increased levels of ROS in the peripheral blood, an elevated ratio of Th17 differentiation, and a decreased ratio of Treg differentiation. ROS levels were positively correlated with the Th17 cell proportion but negatively correlated with the Treg cell proportion. The ROS levels and NLRP3/IL-1ß/caspase-1 expression were up-regulated in CD4+ T cells after H2O2 treatment. Furthermore, there was an increase in Th17 differentiation and a decrease in Treg differentiation. Conversely, the NLRP3/IL-1ß/caspase-1 pathway inhibition reversed the effects of H2O2 treatment, with no significant change in the ROS levels. ROS regulates the Th17/Treg balance in CPP, possibly through the NLRP3/IL-1ß/caspase-1 pathway. This study provides a new perspective on the development of immunotherapy for CPP.

Leaf anatomical alterations reduce cotton's mesophyll conductance under dynamic drought stress conditions.

Drought stress significantly affects cotton's net photosynthetic rate (A) by restraining stomatal (gs ) and mesophyll conductance (gm ) as well as perturbing its biochemical process, resulting in yield reductions. Despite the significant progress in dissecting effects of drought on photosynthesis, the variability observed in cotton's gm , and the mechanisms contributing to that variability under dynamic drought stress conditions are poorly understood. For that reason, a controlled-environment experiment with two cotton genotypes (Dexiamian 1, Yuzaomian 9110), three water levels (soil relative water content: control [75 ± 5]%, moderate drought [60 ± 5]%, severe drought [45 ± 5]%), and two drought durations (10 and 31 days) were conducted. The results indicated that the cotton boll biomass was significantly decreased under 10-day severe drought and 31-day moderate and severe drought. Decreases in gs were later accompanied by decreases in gm and further combined with reductions in electron transport rate, as drought stress progressed in duration and severity, ultimately resulting in significant reductions in A of subtending leaf. Stomatal and mesophyll conductance constraints were the primary factors limiting photosynthesis, while biochemical constraints decreased, as drought stress progressed. Considering gm , its decline was ascribed to increases in the diffusion resistance of CO2 through cytoplasm (rcyt ), under short- or long-term drought, as well as to increases in leaf dry mass (LMA), and decreases in the chloroplast surface area exposed to intercellular air space (Sc /S), under long-term drought. It was concluded that A could be enhanced, under dynamic drought stress conditions, by increasing gm through increasing Sc /S and reducing LMA and rcyt .

Immune repertoire sequencing reveals an abnormal adaptive immune system in COVID-19 survivors.

Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impairs the adaptive immune system during acute infection. Still, it remains largely unclear whether the frequency and functions of T and B cells return to normal after the recovery of Coronavirus Disease 2019 (COVID-19). Here, we analyzed immune repertoires and SARS-CoV-2-specific neutralization antibodies in a prospective cohort of 40 COVID-19 survivors with a 6-month follow-up after hospital discharge. Immune repertoire sequencing revealed abnormal T- and B-cell expression and function with large T cell receptor/B cell receptor clones, decreased diversity, abnormal class-switch recombination, and somatic hypermutation. A decreased number of B cells but an increased proportion of CD19+ CD138+ B cells were found in COVID-19 survivors. The proportion of CD4+ T cells, especially circulating follicular helper T (cTfh) cells, was increased, whereas the frequency of CD3+ CD4- T cells was decreased. SARS-CoV-2-specific neutralization IgG and IgM antibodies were identified in all survivors, especially those recorded with severe COVID-19 who showed a higher inhibition rate of neutralization antibodies. All severe cases complained of more than one COVID-19 sequelae after 6 months of recovery. Overall, our findings indicate that SARS-CoV-2-specific antibodies remain detectable even after 6 months of recovery. Because of their abnormal adaptive immune system with a low number of CD3+ CD4- T cells and high susceptibility to infections, COVID-19 patients might need more time and medical care to fully recover from immune abnormalities and tissue damage.

Cardiac tropoini T (TNNT2) plays a potential oncogenic role in colorectal carcinogenesis.

PURPOSE: Colorectal cancer (CRC) is the third most common cancer in the world. The purpose of this study was to investigate the role of TNNT2 in the proliferation, migration and invasion of CRC cells and its expression in CRC tissues to better understand the regulatory role of TNNT2 in CRC. METHODS: Western blotting (WB) and qPCR were used to detect the expression of TNNT2 in colorectal cancer tissues and paracancerous tissues. CCK-8, colony formation, Transwell and other experiments were used to clarify the role of TNNT2 in the proliferation, migration and invasion of colorectal cancer cells. Changes in TNNT2, EGFR and HER2 mRNA transcription levels were detected by SYBR Real-Time PCR assay, and the effects of TNNT2 overexpression or knockdown on the expression of EGFR, HER2 and EMT-related proteins in CRC cells were determined by WB. TNNT2 and EGFR intreaction was carried out in HCT116 cells by coimmunoprecipitation experiments. RESULTS: The protein and mRNA expression level of TNNT2 in CRC tissues were higher than those in paracancerous tissues. The CCK-8 results suggested that overexpression of TNNT2 significantly promoted the proliferation of HCT116 and RKO cells, and TNNT2 konckdown gets the opposite result; and the colony formation results were the same as tthose of CCK-8 assay. Transwell invasion and migration experiments showed that overexpression of TNNT2 promoted the migration and invasion of HCT116 and PKO cells, and TNNT2 konckdown suppressed the migration and invasion of the these cells. The SYBR Green I real-time PCR method revealed that them RNA levels of TNNT2, EGFR and HER2 in the TNNT2 overexpression group were higher than those in RKO cells. WB showed that overexpressing TNNT2 increased the expression of EGFR and HER2 in HCT16 and RKO cells,decreased the expression of EMT marker E-cadherin, and increased the expression of Vimentin and N-cadherin. Konckdown of TNNT2 decreased the expression of EGFR and HER2, increased the expression of E-cadherin, and decreased the expression of Vimentin and N-cadherin in HCT16 and RKO cells. The immunocoprecipitation experiment showed that there was an interaction between EGFR and TNNT2. CONCLUSION: TNNT2 can promote the proliferation, invasion and metastasis of colorectal cancer cells. There is an interaction between TNNT2 and EGFR protein. TNNT2 can upregulate EGFR and HER2-related proteins in colorectal cancer cells and promote the occurrence of EMT. Therefore, TNNT2 can promote the invasion and metastasis of CRC cells through the EGFR/HER2/EMT signal axis, suggesting that TNNT2 is a potential target of CRC treatment.

Combined effect of elevated temperature and drought stress on carbohydrate metabolism of cotton (Gossypium hirsutum L.) subtending leaves.

High temperatures and drought are expected to become more frequent in the future and last longer than ever before. To investigate their combined effect on leaves subtending cotton boll (LSCB), an experiment was conducted from 2016 to 2018 using a nonheat-tolerant cotton cultivar and a heat-tolerant cultivar. Two temperature regimes with ambient temperature (AT, 31.0/26.4°C) and elevated temperature (ET, 33.4/28.9°C, 2.5°C higher than AT) and three drought treatments with a soil relative water content (SRWC) of 75 ± 5%, 60 ± 5%, and 45 ± 5% were established repeatedly. ET decreased net photosynthetic rate (Pn), initial rubisco activity (4.1.1.39, RuBP) and cytosolicfructose-1,6-bisphosphatase (cy-FBPase; 3.1.3.11) activity, upregulated GhSuSyA, and GhSuSyD expressions, and increased SuSy (2.4.1.13) activity, which led to the decline of the final starch and sucrose contents. Moreover, RuBP, Pn, and starch content all decreased with drop in SRWC levels, but the cy-FBPase and SPS (2.4.1.14) activity increased, which in turn increased sucrose content. Under combined stresses, when the changing trends of ET and drought effects were the same, the decrease of Pn, RuBP, and starch content was greater than under single stress exposure. However, when the changing trends of ET and drought effects were adverse, the combined effects on indicators such as cy-FBPase, SuSy, sucrose content were mostly similar to drought stress. These results indicate that the effect of drought on carbohydrate metabolism in LSCB is more prominent than ET. Thus, the drought effect for carbohydrate metabolism in LSCB may need more attention than ET under combined heat and drought stress.

Auxin and abscisic acid play important roles in promoting glucose metabolism of reactivated young kernels of maize (Zea mays L.).

In maize, young kernels that are less competitive and have poor sink activity often abort. Studies have indicated that such poor competitiveness depends, in part, on the regulation by auxin (IAA) and abscisic acid (ABA). However, the mechanisms for such effects remain unclear. We used pollination-blocking and hand-pollination treatments accompanied by multi-omics and physiological tests, to identify underlying mechanism by which IAA and ABA, along with sugar signaling affect kernel development. Results showed that preventing pollination of the primary ears reactivated kernels in the secondary ears and altered both sugar metabolism and hormone signaling pathways. This was accompanied by increased enzyme activities in carbon metabolism and concentrations of glucose and starch, as well as increased levels of IAA and decreased levels of ABA in the reactivated kernels. Positive and negative correlations were observed between IAA, ABA contents and cell wall invertase (CWIN) activity, and glucose contents, respectively. In vitro culture revealed that the expression of genes involved in glucose utilization was upregulated by IAA, but downregulated by ABA. IAA could promote the expression of ABA signaling genes ZmPP2C9 and ZmPP2C13 but downregulated the expression of Zmnced5, an ABA biosynthesis gene, and ZmSnRK2.10, which is involved in ABA signal transduction. However, these genes showed opposite trends when IAA transport was inhibited. To summarize, we suggest a regulatory model for how IAA inhibits ABA metabolism by promoting the smooth utilization of glucose in reactivated young kernels. Our findings highlight the importance of IAA in ABA signaling by regulating glucose production and transport in maize.

Foliar melatonin ameliorates drought-induced alterations in enzyme activities of sugar and nitrogen metabolisms in cotton leaves.

Sugar and nitrogen metabolisms help plants maintain cellular homeostasis, stress tolerance, and sustainable growth in drought conditions. Melatonin, a potent antioxidant and signaling molecule, appears to mitigate the negative impacts of drought on plants. This study aimed to investigate the potential role of foliar-applied melatonin in ameliorating drought-induced alterations in leaf sugar and nitrogen metabolisms' enzyme activities during cotton flowering and boll formation. To date, no study has examined drought-induced sugar and nitrogen metabolisms' enzyme activity changes in cotton treated with foliar melatonin. Drought levels (FC1 = 75 ± 5%, FC2 = 60 ± 5%, and FC3 = 45 ± 5%) were maintained between 3 and 35 days after flowering (DAF), and melatonin (M) concentrations (0, 25, 50, and 100 µmol L-1 ) were applied at 3 and 21 DAF in a completely randomized design. M100 concentrations at low FC levels significantly enhanced leaf sugar and N-metabolic enzyme activities, such as sucrose synthase (65.56%) and glutamine synthetase (55.24%), compared to plants not treated with melatonin; peaking between 7 and 21 DAF and declining gradually with crop growth. Moreover, the M100 concentrations at all FC levels, particularly FC3, significantly increased the relative expression of GhSusB, GhSusC, SPS1, and SPS3 genes, indicating that melatonin improves leaf sugar and N-metabolism enzymatic activities under drought stress. Therefore, applying M100 concentrations to cotton foliage under FC3 conditions during reproductive stages improves leaf water status, sugar, and N-metabolism enzyme activities, demonstrating melatonin's potent anti-stress, osmoregulatory, and growth-promoting properties in overcoming drought stress in cotton crops. Future research into the molecular mechanisms of melatonin-mediated sugar and nitrogen metabolism enzyme activities in cotton leaves may lead to biotechnological methods to improve drought resilience in cotton and other crops.

Potassium ameliorates cotton (Gossypium hirsutum L.) fiber length by regulating osmotic and K+ /Na+ homeostasis under salt stress.

Potassium (K) application can alleviate cotton salt stress, but the regulatory mechanisms affecting cotton fiber elongation and ion homeostasis are still unclear. A two-year field experiment was conducted to explore the effects of K on the osmolyte contents (soluble sugar, K+ content, and malate) and related enzyme activities during the fiber elongation of two cotton cultivars with contrasting salt sensitivity (CCRI-79; salt tolerant cultivar, and Simian 3; salt-sensitive cultivar). Three K application treatments (0, 150, and 300 kg K2 O ha-1 ) were applied at three soil salinity levels (low salinity, EC = 1.73 ± 0.05 dS m-1 ; medium salinity, EC = 6.32 ± 0.10 dS m-1 ; high salinity, EC = 10.84 ± 0.24 dS m-1 ). K application improved fiber length and alleviated salt stress by increasing the maximum velocity of fiber elongation (Vmax ). The increase rate of K on fiber length decreased with elevating salt stress, and the increase rate of K on Vmax of CCRI-79 was greater than that of Simian3. K application can increase the enzyme activities (phosphoenolpyruvate carboxylase, PEPC, E.C. 4.1.1.31; pyrophosphatase, PPase, E.C. 3.6.1.1; and plasma membrane H+ -ATPase, PM H+ -ATPase, E.C. 3.6.3.14) as well as the content of osmolytes associated with the enzymes mentioned above. K increased the osmolyte contents under salt stress, and the increase in the K+ content of the fibers was much higher than that of soluble sugar and malate. The results of this study indicated K fertilizer application rates regulate the metabolism of osmolytes in cotton fiber development under salt stress, K+ is more critical to fiber elongation.

Persistent white matter changes in recovered COVID-19 patients at the 1-year follow-up.

There is growing evidence that severe acute respiratory syndrome coronavirus 2 can affect the CNS. However, data on white matter and cognitive sequelae at the 1-year follow-up are lacking. Therefore, we explored these characteristics in this study. We investigated 22 recovered coronavirus disease 2019 (COVID-19) patients and 21 matched healthy controls. Diffusion tensor imaging, diffusion kurtosis imaging and neurite orientation dispersion and density imaging were performed to identify white matter changes, and the subscales of the Wechsler Intelligence scale were used to assess cognitive function. Correlations between diffusion metrics, cognitive function and other clinical characteristics were then examined. We also conducted subgroup analysis based on patient admission to the intensive care unit. The corona radiata, corpus callosum and superior longitudinal fasciculus had a lower volume fraction of intracellular water in the recovered COVID-19 group than in the healthy control group. Patients who had been admitted to the intensive care unit had lower fractional anisotropy in the body of the corpus callosum than those who had not. Compared with the healthy controls, the recovered COVID-19 patients demonstrated no significant decline in cognitive function. White matter tended to present with fewer abnormalities for shorter hospital stays and longer follow-up times. Lower axonal density was detected in clinically recovered COVID-19 patients after 1 year. Patients who had been admitted to the intensive care unit had slightly more white matter abnormalities. No significant decline in cognitive function was found in recovered COVID-19 patients. The duration of hospital stay may be a predictor for white matter changes at the 1-year follow-up.

Prognostic roles of hematological indicators for the efficacy and prognosis of immune checkpoint inhibitors in patients with advanced tumors: a retrospective cohort study.

BACKGROUND: Immunocheckpoint inhibitor(ICI) is a major breakthrough in tumor treatment. It can activate the patient's own immune system and play an anti-tumor role, but not all patients can benefit from it. At present, there is still a lack of effective biomarkers to guide clinical application. The systemic immune inflammation(SII) index reflects the systemic inflammatory state and immune state of patients. Prognostic nutrition index(PNI) can be used to evaluate immune status of patients. Therefore, SII and PNI indexes may have some value in predicting the efficacy and prognosis of immunotherapy, but there is still a lack of relevant research. The purpose of our study was to explore the influence of SII and PNI index on the efficacy and prognosis of immunotherapy. METHODS: A total of 1935 patients treated with ICIs treatment in the Fourth Hospital of Hebei Medical University from November 2016 to October 2021 were retrospectively collected. 435 patients who met the inclusion criteria and did not meet the exclusion criteria. The imaging data, blood results of each patient were collected within 1 week before ICIs treatment. The neutrophil lymphocyte ratio(NLR), platelet lymphocyte ratio(PLR), monocyte lymphocyte ratio(MLR), PNI,systemic inflammatory response index(SIRI),neutrophil-eosinophil ratio(NER) was calculated. The patients were followed up by in-patient, out-patient reexamination and telephone contact, and the efficacy evaluation and survival status were recorded. The deadline of follow-up: January 2021. SPSS-24.0 software was employed for statistical analysis. RESULTS: Among the 435 patients receiving ICI treatment, 61,236 and 138 patients were evaluated respectively as partial response (PR), stable disease (SD) and progressive disease (PD). The overall response rate(ORR) and disease control rate (DCR) of this cohort were 14.0% and 68.3%, respectively. Median progression-free survival (mPFS) is 4.0 months, The overall survival (mOS) of this cohort is 6.8 months. Multivariate analysis showed that SIRI(Hazard Ratio, HR = 1.304, P = 0.014), PNI (HR = 0.771, P = 0.019), prealbumin (PAB) (HR = 0.596, P = 0.001), and PNI(HR = 0.657, P = 0.008) were independent risk factors for PFS and OS, respectively. CONCLUSIONS: Patients with high SIRI value and low PNI value before ICI treatment have shorter PFS. Patients with higher PNI value have better prognosis. Therefore, hematological indicators may become predictors of immunotherapy.

Design of a Two-Dimensional Conveyor Platform with Cargo Pose Recognition and Adjustment Capabilities.

Linear conveyors, traditional tools for cargo transportation, have faced criticism due to their directional constraints, inability to adjust poses, and single-item conveyance, making them unsuitable for modern flexible logistics demands. This paper introduces a platform designed to convey and adjust cargo boxes according to their spatial positions and orientations. Additionally, a cargo pose recognition algorithm that integrates image and point cloud data are presented. By aligning depth camera data, the axis-aligned bounding box (AABB) point serves as the image's region of interest (ROI). Peaks extracted from the image's Hough transform are refined using RANSAC-based point cloud linear fitting, then integrated with the point cloud's oriented bounding box (OBB). Notably, the algorithm eliminates the need for deep learning and registration, enabling its use in rectangular cargo boxes of various sizes. A comparative experiment using accelerometer sensors for pose acquisition revealed a deviation of <0.7° between the two processes. Throughout the real-time adjustments controlled by the experimental platform, cargo angles consistently remained stable. The proposed two-dimensional conveyance platform, compared to existing methods, exhibits simplicity, accurate recognition, enhanced flexibility, and wide applicability.

Glutathione-Responsive Chemodynamic Therapy of Manganese(III/IV) Cluster Nanoparticles Enhanced by Electrochemical Stimulation via Oxidative Stress Pathway.

Escalating the level of reactive oxygen species (ROS) in a tumor microenvironment is one of the effective strategies to improve the efficacy of anticancer therapy. In this work, manganese cluster nanoparticles (Mn12) encapsulated with heparin (Mn12-heparin) were developed as a chemodynamic therapeutic agent for cancer treatment by raising ROS levels in tumor cells via cascade reactions. The manganese cluster is a cluster of mixed valence (III/IV) with acetate as the ligand. The cluster is readily subject to reduction by glutathione (GSH) to release Mn(II), which reacts with H2O2 to generate hydroxyl radicals via a Fenton-like pathway. The generation of hydroxyl radicals could be enhanced by the stimulation of an external alternative electric field during which GSH acts as an electron mediator to enhance the release of Mn(II) from the cluster. The relatively high levels of both H2O2 and GSH and the acidic environment in tumor cells strengthen its specificity when the manganese cluster system is employed to suppress or eliminate tumors. Both in vitro and in vivo results suggest that, in addition to the cytotoxicity imposed by the raised ROS level due to the presence of Mn(II) species, the depletion of endogenous GSH leads indirectly to the inhibition of glutathione peroxidase 4 (GPX4), consequently raising the lipid peroxidation (LPO) level to cause ferroptosis. The apoptosis and ferroptosis jointly render the manganese-based agent potent efficacy with tumor-targeting specificity in antitumor treatment under electric stimulation.

Unexpected favorable outcome to sintilimab monotherapy in a relapse pancreatic ductal adenocarcinoma patient with high tumor mutational burden: a case report.

The reason that immune checkpoint inhibitors have not been widely applied to pancreatic cancer treatment is probably because of low immunogenicity or dense stromal fibrosis. Recently, only pembrolizumab was recommended for DNA mismatch repair deficiency or high microsatellite instability by National Comprehensive Cancer Network guideline. Pancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of pancreatic cancer, with a poor overall survival rate, the value of immunotherapy for PDAC needs more research. Here, we report a 56-year-old man suffered from PDAC with liver metastasis after radical surgery. The next-generation sequencing result demonstrated that it had remarkably high tumor mutational burden (TMB) of 49.92 Muts/Mb and microsatellite stability. Sintilimab (anti-PD-1) monotherapy was continuously administrated after failure of combined chemotherapy in second line, achieving stable disease within 22 months and few immunotherapy-related adverse events. To our knowledge, this is the first time to report a good outcome achieving 22 months with progression-free survival after PDAC metastasis with monotherapy of sintilimab. TMB may serve as a potential efficacy-related predictor in PDAC patients with sintilimab and help physicians make optimum clinical strategy.

Effects of elevated air temperature coupling with soil drought on carbohydrate metabolism and oil synthesis during cottonseed development.

Cotton, as the fifth-largest oilseed crop, often faces the coupling stress of heat and drought. Still, the effects of combined stress on cottonseed oil synthesis and its closely related carbon metabolism are poorly investigated. To this end, experiments were conducted with two cultivars (Sumian 15 and PHY370WR) under two temperature regimes: ambient temperature (AT) and elevated temperature (ET, which was 2.5°C-2.7°C higher than AT) and three water regimes: optimum soil moisture (soil relative water content [SRWC] at 75% ± 5%), and drought (SD) including SRWC 60% ± 5% and SRWC 45% ± 5%, during 2016-2018. Results showed that ET plus SD decreased cottonseed kernel yield, seed index, kernel weight, and kernel percentage more than either single stress. The content of hexoses, the carbon skeleton source for oil synthesis, was decreased by ET while increased by SD. The combined stress increased the hexose content by increasing the activities of sucrose synthase (SuSy, EC 2.4.1.13) and invertase (Inv, EC 3.2.1.26) and upregulating GhSuSy expression; however, hexose content under combined stress was lower than that under SD alone. Increased oil content under SD was attributed to the high phosphoenolpyruvate carboxylase (PEPCase, EC 4.1.1.31), acetyl-CoA carboxylase (ACCase, EC 6.4.1.2), and diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) activities, whereas the opposite effects were seen under ET. Under combined stress, although ACCase activity decreased, PEPCase and DGAT activities, and GhPEPC-1 and GhDGAT-1 expression upregulated, enhancing carbon flow into oil metabolism and triacylglycerol synthesis, ultimately generating higher oil content.

Foliar melatonin stimulates cotton boll distribution characteristics by modifying leaf sugar metabolism and antioxidant activities during drought conditions.

Drought is a severe abiotic stress affecting the plant's antioxidant system and interrupting compatible solute translocation processes, which leads to low productivity. Melatonin acts as a common growth regulator enhancing the plants defense system and regulates sugar metabolism in challenging environments. Melatonin treatments enable plants to be tolerant to abiotic stresses via enhancing their recovery potential, but its impact using various concentrations has not yet been studied in leaf physiological aspects when applied to cotton foliage during their peak flowering and boll loading stage. The overall objective of this research was to facilitate cotton boll distribution characteristics by modifying cotton leaf sugar metabolism and antioxidant activity by applying foliar melatonin (0, 25, 50, and 100 µmol l-1 ) under drought levels with a relative soil water content of 75%, 60%, and 45% ± 5 (FC1, FC2, and FC3, respectively). Higher rates of melatonin application (100 µmol l-1 ) enhanced boll distribution characteristics and controlled the boll shedding rate during drought conditions. An increase in melatonin rates proved to be more helpful in stimulating cotton sympodial leaf physiological attributes, including leaf gas exchange parameters, sugar metabolism, proline content, and antioxidants defense system as compared with less or no melatonin application during all FC conditions and showed the most significant effect at a higher melatonin concentration (M100) at 7-21 DAF. The total proline content and antioxidant activity were enhanced in the M100 treatment during all FC levels, which caused a reduction in the total malondialdehyde (MDA) contents and hydrogen peroxide (H2 O2 ) concentrations in cotton leaves. Moreover, sugar metabolism responsible genes GhSusA and SPS2 showed an upsurge in expression levels and enhanced sucrose degradation in M100 treatments during all FC levels. Furthermore, cotton boll attributes showed also a positive relation with leaf physiological and gas exchange attributes. The results suggested that foliar melatonin application during the flowering initiation stage improved the overall performance and is helpful for cotton crops productivity against drought stress.