Nitrogen mitigates the negative effects of combined heat and drought stress on winter wheat by improving physiological characteristics.

Extreme drought stress is often accompanied by heat stress after anthesis in winter wheat. Whether nitrogen (N) can mitigate the damage caused by combined stress on wheat plants by regulating root physiological characteristics is still unclear. Thus, this study aimed to study the effects of combined heat and drought stress on photosynthesis, leaf water relations, root antioxidant system, osmoregulatory, and yield in wheat to reveal the physiological mechanism of N regulating the adverse impacts of combined stress on wheat. Heat and drought stress markedly reduced photosynthesis, leaf water content, root vitality, and bleeding sap. The combination of heat and drought strengthens these changes. Within a certain stress range, the increase in soluble sugar and proline contents and the activities of superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase under combined stress effectively alleviated the oxidative damage. Compared with those under high N application (N3), wheat plants under low N application (N1) maintained higher yield and yield components under combined stress; the number of grains per spike, 1000-grain weight, and yield increased by 13.65%, 9.07%, and 15.33%, respectively, under N1 compared with those under N3 treatment, which may be attributed to the greater maintenance of photosynthesis, leaf water status, root vitality, and antioxidant and osmoregulation capacities. In summary, reduced N application mitigated the damage caused by combined heat and drought stress in wheat by improving root physiological characteristics and enhanced adaptability to combined stress, which is an appropriate strategy to compensate for yield losses.

Diagnostic performance of 18F-labeled PSMA PET/CT in patients with biochemical recurrence of prostate cancer: a systematic review and meta-analysis.

BACKGROUND: After initial treatment of prostate cancer, increases in prostate-specific antigen (PSA) levels commonly signify potential relapse or metastasis. 18F-labeled prostate-specific membrane antigen (PSMA) is considered a promising treatment due to its favorable physical properties. PURPOSE: To investigate the diagnostic value of 18F-PSMA PET/CT for the recurrence and/or metastasis of biochemical recurrence of prostate cancer (BRPca). MATERIAL AND METHODS: A comprehensive literature search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library databases. Combined sensitivity and specificity values for the use of 18F-PSMA PET/CT in patients with BRPca were obtained. The quality of the studies was tested using the Diagnostic Accuracy Research Quality Assessment tool. Meta-analysis was performed using STATA 15 software, and heterogeneity was subsequently tested. RESULTS: A total of 16 studies (1162 patients) were enrolled and had significant heterogeneity. The pooled sensitivity, specificity, and AUC values for 18F-PSMA PET/CT in the diagnosis of prostate recurrence and/or metastasis were 0.93 (0.89-0.95), 0.94 (0.85-0.98), and 0.96 (0,94-0.98), respectively. Meta-regression analyses showed that the sources of heterogeneity did not relate to ligands, study designs, or participants. The pooled sensitivity and specificity values of 18F-DCFPyL PET/CT were 0.90 (0.85-0.94) and 0.89 (0.85-0.93), respectively. The pooled sensitivity and specificity values of 18F-PSMA-1007 PET/CT were 0.89 (0.85-0.93) and 0.93 (0.70-0.99), respectively. The per-patient pooled sensitivity and specificity values were 0.92 (0.86-0.96) and 0.83 (0.41-0.97), respectively. The per-lesion pooled sensitivity and specificity values were 0.91 (0.86-0.94) and 0.91 (0.86-0.94), respectively. CONCLUSION: According to our meta-analysis, 18F-PSMA PET/CT has the potential to be critical for the diagnosis of recurrence and/or metastasis in patients with BRPca.

A novel murine model of combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

Primary liver cancer (PLC) is a common gastrointestinal malignancy worldwide. While hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two major pathologic types of PLC, combined HCC and ICC (cHCC-ICC) is a relatively rare subtype that shares both hepatocyte and cholangiocyte differentiation. However, the molecular feature of this unique tumor remains elusive because of its low incidence and lack of a suitable animal model. Herein, we generated a novel spontaneous cHCC-ICC model using a Sleeping Beauty-dependent transposon plasmid co-expressing oncogenic Myc and AKT1 and a CRISPR-Cas9 plasmid expressing single-guide RNA targeting p53 into mouse hepatocytes via in situ electroporation. The histological and transcriptional analysis confirmed that this model exhibits cHCC-ICC features and activates pathways committing cHCC-ICC formation, such as TGF-ß, WNT, and NF-κB. Using this model, we further screened and identified LAMB1, a protein involved in cell adhesion and migration, as a potential therapeutic target for cHCC-ICC. In conclusion, our work presents a novel genetic cHCC-ICC model and provides new insights into cHCC-ICC.

Tumor cell-imposed iron restriction drives immunosuppressive polarization of tumor-associated macrophages.

BACKGROUND: Tumor-associated macrophages (TAM) are immunosuppressive cells that contribute to impaired anti-cancer immunity. Iron plays a critical role in regulating macrophage function. However, it is still elusive whether it can drive the functional polarization of macrophages in the context of cancer and how tumor cells affect the iron-handing properties of TAM. In this study, using hepatocellular carcinoma (HCC) as a study model, we aimed to explore the effect and mechanism of reduced ferrous iron in TAM. METHODS: TAM from HCC patients and mouse HCC tissues were collected to analyze the level of ferrous iron. Quantitative real-time PCR was used to assess M1 or M2 signature genes of macrophages treated with iron chelators. A co-culture system was established to explore the iron competition between macrophages and HCC cells. Flow cytometry analysis was performed to determine the holo-transferrin uptake of macrophages. HCC samples from The Cancer Genome Atlas (TCGA) were enrolled to evaluate the prognostic value of transferrin receptor (TFRC) and its relevance to tumor-infiltrating M2 macrophages. RESULTS: We revealed that ferrous iron in M2-like TAM is lower than that in M1-like TAM. In vitro analysis showed that loss of iron-induced immunosuppressive M2 polarization of mouse macrophages. Further experiments showed that TFRC, the primary receptor for transferrin-mediated iron uptake, was overexpressed on HCC cells but not TAM. Mechanistically, HCC cells competed with macrophages for iron to upregulate the expression of M2-related genes via induction of HIF-1α, thus contributing to M2-like TAM polarization. We further clarified the oncogenic role of TFRC in HCC patients by TCGA. TFRC is significantly increased in varieties of malignancies, including HCC, and HCC patients with high TFRC levels have considerably shortened overall survival. Also, TFRC is shown to be positively related to tumor-infiltrating M2 macrophages. CONCLUSIONS: Collectively, we identified iron starvation through TFRC-mediated iron competition drives functional immunosuppressive polarization of TAM, providing new insight into the interconnection between iron metabolism and tumor immunity.

Complete genome sequencing of Peyer's patches-derived Lactobacillus taiwanensis CLG01, a potential probiotic with antibacterial and immunomodulatory activity.

BACKGROUND: The genus Lactobacillus is an important component of the gastrointestinal tract of human and animals and commonly considered as probiotic. L. taiwanensis has long been proposed to be a probiotic whereas understanding on this species is still in its infancy. Genomic information of L. taiwanensis is fairly limited. Extensive characterization of its beneficial traits is needed. RESULTS: A new strain CLG01 of L. taiwanensis was isolated from mouse Peyer's patches. We established its probiotic profile through in vitro experiments. Complete genome of this strain was also sequenced and analyzed. L. taiwanensis CLG01 showed robust tolerance to acid and a degree of tolerance to bile salt with a promising antibacterial activity against a broad spectrum of pathogenic bacteria. In vitro treatment of mouse RAW 264.7 macrophage cells with heat-killed bacteria and bacterial supernatant of L. taiwanensis CLG01 resulted in enhancement of immune responses and upregulated expression of TNF-α and IL-6. The strain CLG01 also increased the IL-10 production of macrophages when co-treated with lipopolysaccharide (LPS). Complete genome of L. taiwanensis CLG01 contained a 1.89 Mb chromosome and two plasmids. Further genomic analysis revealed the presence of genes related to its resistance to different stresses and the beneficial effects mentioned above. Moreover, biosynthetic gene clusters (BGCs) encoding antimicrobial peptides, like bacteriocin, linear azol(in)e-containing peptide (LAP) and lanthipeptide, were also identified in the genome of L. taiwanensis CLG01. CONCLUSIONS: L. taiwanensis CLG01, isolated from mouse Peyer's patches, is the first L. taiwanensis strain with both phenotypes and genotypes systematically studied. These preliminary data confirmed the role of L. taiwanensis CLG01 as a potential probiotic candidate with antibacterial and immunomodulatory activity, which provide insight for further investigation to this species.

Real-time artificial intelligence for endoscopic diagnosis of early esophageal squamous cell cancer (with video).

BACKGROUND AND AIMS: Endoscopic diagnosis of early esophageal squamous cell cancer (ESCC) is complicated and dependent on operators' experience. This study aimed to develop an artificial intelligence (AI) model for automatic diagnosis of early ESCC. METHODS: Non-magnifying and magnifying endoscopic images of normal/noncancerous lesions, early ESCC, and advanced esophageal cancer (AEC) were retrospectively obtained from Qilu Hospital of Shandong University. A total of 10,988 images from 5075 cases were chosen for training and validation. Another 2309 images from 1055 cases were collected for testing. One hundred and four real-time videos were also collected to evaluate the diagnostic performance of the AI model. The diagnostic performance of the AI model was compared with endoscopists by magnifying images and the assistant efficiency of the AI model for novices was evaluated. RESULTS: The AI diagnosis for non-magnifying images showed a per-patient accuracy, sensitivity, and specificity of 99.5%, 100%, 99.5% for white light imaging, and 97.0%, 97.2%, 96.4% for optical enhancement/iodine straining images. Regarding diagnosis for magnifying images, the per-patient accuracy, sensitivity, and specificity were 88.1%, 90.9%, and 85.0%. The diagnostic accuracy of the AI model was similar to experts (84.5%, P = 0.205) and superior to novices (68.5%, P = 0.005). The diagnostic performance of novices was significantly improved by AI assistance. When it comes to the diagnosis for real-time videos, the AI model showed acceptable performance as well. CONCLUSIONS: The AI model could accurately recognize early ESCC among noncancerous mucosa and AEC. It could be a potential assistant for endoscopists, especially for novices.

[Identification of Armeniacae Semen Amarum and Persicae Semen from different origins based on near infrared hyperspectral imaging technology].

In order to establish a rapid and non-destructive evaluation method for the identification of Armeniacae Semen Amarum and Persicae Semen from different origins, the spectral information of Armeniacae Semen Amarum and Persicae Semen in the range of 898-1 751 nm was collected based on hyperspectral imaging technology. Armeniacae Semen Amarum and Persicae Semen from different origins were collected as research objects, and a total of 720 Armeniacae Semen Amarum samples and 600 Persicae Semen samples were used for authenticity discrimination. The region of interest(ROI) and the average reflection spectrum in the ROI were obtained, followed by comparing five pre-processing methods. Then, partial least squares discriminant analysis(PLS-DA), support vector machine(SVM), and random forest(RF) method were established for classification models, which were evaluated by the confusion matrix of prediction results and receiver operating characteristic curve(ROC). The results showed that in the three sample sets, the se-cond derivative pre-processing method and PLS-DA were the best model combinations. The classification accuracy of the test set under the 5-fold cross-va-lidation was 93.27%, 96.19%, and 100.0%, respectively. It was consistent with the confusion matrix of the predicted results. The area under the ROC curve obtained the highest values of 0.992 3, 0.999 6, and 1.000, respectively. The study revealed that the near-infrared hyperspectral imaging technology could accurately identify the medicinal materials of Armeniacae Semen Amarum and Persicae Semen from different origins and distinguish the authentication of these two varieties.

[Fusion of spectrum and image features to identify Glycyrrhizae Radix et Rhizoma from different origins based on hyperspectral imaging technology].

To identify Glycyrrhizae Radix et Rhizoma from different geographical origins, spectrum and image features were extracted from visible and near-infrared(VNIR, 435-1 042 nm) and short-wave infrared(SWIR, 898-1 751 nm) ranges based on hyperspectral imaging technology. The spectral features of Glycyrrhizae Radix et Rhizoma samples were extracted from hyperspectral data and denoised by a variety of pre-processing methods. The classification models were established by using Partial Least Squares Discriminate Analysis(PLS-DA), Support Vector Classification(SVC) and Random Forest(RF). Meanwhile, Gray-Level Co-occurrence matrix(GLCM) was employed to extract textural variables. The spectrum and image data were implemented from three dimensions, including VNIR and SWIR fusion, spectrum and image fusion, and comprehensive data fusion. The results indicated that the spectrum in SWIR range performed better classification accuracy than VNIR range. Compared with other four pre-processing methods, the second derivative method based on Savitzky-Golay(SG) smoothing exhibited the best performance, and the classification accuracy of PLS-DA and SVC models were 93.40% and 94.11%, separately. In addition, the PLS-DA model was superior to SVC and RF models in terms of classification accuracy and model generalization capability, which were evaluated by confusion matrix and receiver operating characteristic curve(ROC). Comprehensive data fusion on SPA bands achieved a classification accuracy of 94.82% with only 28 bands. As a result, this approach not only greatly improved the classification efficiency but also maintained its accuracy. The hyperspectral imaging system, a non-invasively, intuitively and quickly identify technology, could effectively distinguish Glycyrrhizae Radix et Rhizoma samples from different origins.

Impact of a real-time automatic quality control system on colorectal polyp and adenoma detection: a prospective randomized controlled study (with videos).

BACKGROUND AND AIMS: Quality control can decrease variations in the performance of colonoscopists and improve the effectiveness of colonoscopy to prevent colorectal cancers. Unfortunately, routine quality control is difficult to carry out because a practical method is lacking. The aim of this study was to develop an automatic quality control system (AQCS) and assess whether it could improve polyp and adenoma detection in clinical practice. METHODS: First, we developed AQCS based on deep convolutional neural network models for timing of the withdrawal phase, supervising withdrawal stability, evaluating bowel preparation, and detecting colorectal polyps. Next, consecutive patients were prospectively randomized to undergo routine colonoscopies with or without the assistance of AQCS. The primary outcome of the study was the adenoma detection rate (ADR) in the AQCS and control groups. RESULTS: A total of 659 patients were enrolled and randomized. A total of 308 and 315 patients were analyzed in the AQCS and control groups, respectively. AQCS significantly increased the ADR (0.289 vs 0.165, P < .001) and the mean number of adenomas per procedure (0.367 vs 0.178, P < .001) compared with the control group. A significant increase was also observed in the polyp detection rate (0.383 vs 0.254, P = .001) and the mean number of polyps detected per procedure (0.575 vs 0.305, P < .001). In addition, the withdrawal time (7.03 minutes vs 5.68 minutes, P < .001) and adequate bowel preparation rate (87.34% vs 80.63%, P = .023) were superior for the AQCS group. CONCLUSIONS: AQCS could effectively improve the performance of colonoscopists during the withdrawal phase and significantly increase polyp and adenoma detection. (Clinical trial registration number: NCT03622281.).

Endocuff-assisted colonoscopy versus cap-assisted colonoscopy for adenoma detection rate: A meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Add-on devices have been widely used in clinical practice. The aim of this meta-analysis was to compare the adenoma detection rate between Endocuff-assisted colonoscopy (EAC) and cap-assisted colonoscopy (CAC). METHODS: PubMed, EMBASE, SCOPUS, and Cochrane databases were searched. Outcomes included adenoma detection rate, cecal intubation rate, cecal intubation time, and withdrawal time. Dichotomous data were pooled to obtain the odds ratio or risk ratio. Continuous data were pooled using the mean difference. RESULTS: Of the 240 articles reviewed, six randomized controlled trials were included, with a total of 1994 patients. In the meta-analysis, no statistical difference in adenoma detection rate was detected between EAC and CAC (47.0% vs 45.1%; P = 0.33). EAC significantly improved detection rate of diminutive adenomas/polyps compared with CAC (P = 0.01). Cecal intubation was achieved in 96.5% in EAC group and 97.9% in CAC group (P = 0.04). Besides, no statistical difference was found in cecal intubation time (P = 0.86), withdrawal time (P = 0.88), small adenomas/polyps (P = 0.60), or large adenomas/polyps (P = 0.95). CONCLUSION: EAC and CAC have their respective merits. EAC significantly improve the detection of diminutive adenomas/polyps. CAC was better in cecal intubation rate.

[Studies on the methodology for quality control in Chinese medicine manufacturing process based on knowledge graph].

According to the requirements for developing the quality control technology in Chinese medicine( CM) manufacturing process and the practical scenarios in applying a new generation of artificial intelligence to CM industry,we present a method of constructing the knowledge graph( KG) for CM manufacture to solve key problems about quality control in CM manufacturing process.Based on the above,a " pharmaceutical industry brain" model for CM manufacture has been established. Further,we propose founding the KG-based methodology for quality control in CM manufacturing process,and briefly describe the design method,system architecture and main functions of the KG system. In this work,the KG for manufacturing Shuxuening Injection( SXNI) was developed as a demonstration study. The KG version 1. 0 platform for intelligent manufacturing SXNI has been built,which could realize technology leap of the quality control system in CM manufacturing process from perceptual intelligence to cognitive intelligence.

Drought stimulus enhanced stress tolerance in winter wheat (Triticum aestivum L.) by improving physiological characteristics, growth, and water productivity.

The impact of drought events on the growth and yield of wheat plants has been extensively reported; however, limited information is available on the changes in physiological characteristics and their effects on the growth and water productivity of wheat after repeated drought stimuli. Moreover, whether appropriate drought stimulus can improve stress resistance in plants by improving physiological traits remains to be explored. Thus, in this study, a pot experiment was conducted to investigate the effects of intermittent and persistent mild [65%-75% soil water-holding capacity (SWHC)], moderate (55%-65% SWHC), and severe drought (45%-55% SWHC) stress on the growth, physiological characteristics, yield, and water-use efficiency (WUE) of winter wheat. After the second stress stimulus, persistent severe drought stress resulted in 30.98%, 234.62%, 53.80%, and 31.00% reduction in leaf relative water content, leaf water potential, photosynthetic rate (Pn), and indole-3-acetic acid content (IAA), respectively, compared to the control plants. However, abscisic acid content, antioxidant enzyme activities, and osmoregulatory substance contents increased significantly under drought stress, especially under persistent drought stress. After the second rehydration stimulus (ASRR), the actual and maximum efficiency of PSII and leaf water status in the plants exposed to intermittent moderate drought (IS2) stress were restored to the control levels, resulting in Pn being 102.56% of the control values; instantaneous WUE of the plants exposed to persistent severe drought stress was 1.79 times that of the control plants. In addition, the activities of superoxide dismutase, peroxidase, catalase, and glutathione reductase, as well as the content of proline, under persistent mild drought stress increased by 52.98%, 33.47%, 51.95%, 52.35%, and 17.07% at ASRR, respectively, compared to the control plants, which provided continuous antioxidant protection to wheat plants. This was also demonstrated by the lower H2O2 and MDA contents after rehydration. At ASRR, the IAA content in the IS2 and persistent moderate drought treatments increased by 36.23% and 19.61%, respectively, compared to the control plants, which favored increased aboveground dry mass and plant height. Compared to the control plants, IS2 significantly increased wheat yield, WUE for grain yield, and WUE for biomass, by 10.15%, 32.94%, and 33.16%, respectively. Collectively, IS2 increased grain growth, yield, and WUE, which could be mainly attributed to improved physiological characteristics after drought-stimulated rehydration.

A Retrospective Analysis of the Computed Tomography Findings and Diagnosis of 53 Cases of Elastofibroma in the Infrascapular Region.

OBJECTIVE: In this work, we have used histopathology as the gold standard for the diagnosis, calculated the sensitivity and positive predictive value (PPV) of computed tomography (CT), and analyzed the CT and clinical characteristics of pathologically proven elastofibromas. METHODS: A systematic retrospective analysis was performed on all patients with infrascapular lesions who were treated in the hospital from 2006 to 2018. CT and histopathological examinations were performed for all cases, and the CT sensitivity and PPV for the diagnosis of elastofibroma were calculated. 12 of 53 cases (20 lesions) underwent enhanced CT scan after CT plain scan, and the related clinical and CT features of elastofibromas have been discussed. RESULTS: Of the 54 patients treated during the study, CT diagnosis was consistent with histopathology in 53 cases. One was a false-positive patient. The PPV and sensitivity of the CT in the diagnosis of elastofibroma were 93.3% (95% CI 68.0%-99.8%) and 100%, respectively. The CT values of 12 patients with 20 lesions on plain and enhanced scans were statistically significant (P=0.001). The prevalence of elastofibromas in males and females was statistically significant (P=.000). There was no statistically significant difference in the incidence of left and right elastofibromas (P=0.752). There was no significant difference in the volume of left and right lesions (P=0.209) and the volume of elastofibromas between males and females (P=.474). CONCLUSION: CT is the most practical tool for the evaluation of elastofibromas in the infrascapular region.

Transferrin receptor 1 promotes hepatocellular carcinoma progression and metastasis by activating the mTOR signaling pathway.

BACKGROUND: Aberrant iron metabolism is commonly observed in multiple tumor types, including hepatocellular carcinoma (HCC). However, as the key regulator of iron metabolism involved in iron absorption, the role of transferrin receptor (TFRC) in HCC remains elusive. METHODS: The mRNA and protein expression of TFRC were evaluated in paired HCC and adjacent non-tumor specimens. The correlation between TFRC level and clinicopathological features or prognostic significance was also analyzed. The role of TFRC on biological functions was finally studied in vitro and in vivo. RESULTS: The TFRC level was remarkably upregulated in HCC tissues compared to paired peritumor tissues. Overexpressed TFRC positively correlated with serum alpha-fetoprotein, carcinoembryonic antigen, and poor tumor differentiation. Multivariate analysis demonstrated that upregulated TFRC was an independent predictive marker for poorer overall survival and disease-free survival in HCC patients. Loss of TFRC markedly impaired cell proliferation and migration in vitro and notably suppressed HCC growth and metastasis in vivo, while overexpression of TFRC performed an opposite effect. Mechanistically, the mTOR signaling pathway was downregulated with TFRC knockdown, and the mTOR agonist MHY1485 completely reversed the biological inhibition in HCC cells caused by TFRC knockdown. Furthermore, exogenous ferric citrate (FAC) or iron chelator reversed the changed biological functions and signaling pathway expression of HCC cells caused by TFRC knockdown or overexpression, respectively. CONCLUSIONS: Our study indicates that TFRC exerts an oncogenic role in HCC and may become a promising therapeutic target to restrain HCC progression.

Multi-Omics profiling identifies aldehyde dehydrogenase 2 as a critical mediator in the crosstalk between Treg-mediated immunosuppression microenvironment and hepatocellular carcinoma.

Dysregulation of the aldehyde dehydrogenase (ALDH) family has been implicated in various pathological conditions, including cancer. However, a systematic evaluation of ALDH alterations and their therapeutic relevance in hepatocellular carcinoma (HCC) remains lacking. Herein, we found that 15 of 19 ALDHs were transcriptionally dysregulated in HCC tissues compared to normal liver tissues. A four gene signature, including ALDH2, ALDH5A1, ALDH6A1, and ALDH8A1, robustly predicted prognosis and defined a high-risk subgroup exhibiting immunosuppressive features like regulatory T cell (Tregs) infiltration. Single-cell profiling revealed selective overexpression of tumor necrosis factor receptor superfamily member 18 (TNFRSF18) on Tregs, upregulated in high-risk HCC patients. We identified ALDH2 as a tumor suppressor in HCC, with three novel phosphorylation sites mediated by protein kinase C zeta that enhanced enzymatic activity. Mechanistically, ALDH2 suppressed Tregs differentiation by inhibiting ß-catenin/TGF-ß1 signaling in HCC. Collectively, our integrated multi-omics analysis defines an ALDH-Tregs-TNFRSF18 axis that contributes to HCC pathogenesis and represents potential therapeutic targets for this aggressive malignancy.

Individual and combined effects of heat and drought and subsequent recovery on winter wheat (Triticum aestivum L.) photosynthesis, nitrogen metabolism, cell osmoregulation, and yield formation.

Extreme temperatures and droughts are considered as the two main factors that limit wheat growth and production. Although responses of wheat plants to heat and drought stress have been extensively investigated, little is known about the extent to which wheat plants can recover after stress relief. In this study, a winter wheat pot experiment was conducted to evaluate the growth, physiological activities, and yield formation responses of wheat to stress and recovery periods under heat stress (36 °C, daily maximum temperature), drought (45-55% of soil water holding capacity), and combined stress conditions. Heat and drought stress significantly reduced photosynthesis, leaf relative water content (LRWC), leaf water potential (LWPnoon), and nitrogen metabolism enzyme activities and increased electrolyte leakage. These parameters showed significant interactions between heat and drought stress. Beneficial osmoregulation of membrane stability was observed in stressed plants because of the accumulation of proline and soluble sugars. Within a range of stresses, the abovementioned physiological processes of individual heat- and drought-stressed plants recovered to levels comparable to those of the control. The recovery capacities of the physiological traits decreased gradually with increasing stress duration, particularly under combined stress. The recovery of LWPnoon and LRWC contributed to the improved photosynthetic performance after stress relief. The combined stress caused greater yield losses than individual heat and drought stress, which was mainly attributed to low levels of thousand grain weight (TGW), the number of grains per ear, and the grain filling rate. After stress relief, the recovery of proline content, glutamine synthetase activity, photosynthetic rate, and LRWC were closely associated with grain yield and thousand grain weight. Collectively, these findings contribute to a better understanding of the coordinated responses of winter wheat during the combined heat and drought stress and recovery periods.

Photosynthetic, antioxidant activities, and osmoregulatory responses in winter wheat differ during the stress and recovery periods under heat, drought, and combined stress.

There will be longer and more intense periods of heat and drought stress in the future for terrestrial ecosystems. Although the responses of wheat plants to heat and drought stress alone have been extensively investigated, little is known about the extent to which their recovery can be assured after stress relief. In this study, a winter wheat pot experiment was conducted to investigate the changes in photosynthetic performance, antioxidant activity, osmoregulation, and membrane lipid peroxidation under heat stress (36 °C), drought (45-55% of soil water holding capacity), and combined stress conditions. The results showed that heat and drought stress significantly reduced the photosynthetic rate and the contents of chlorophyll and carotenoid. Superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione reductase (GR) activities were greatly activated by heat and drought stress to scavenge overproduced superoxide anion (O2-). Plants exhibited positive osmoregulation through the synthesis of soluble protein (SP), soluble sugar (SS), and proline (Pro) to improve membrane stability. Within a range of stress, combined heat and drought stress exhibited significant interactive effects in the above mentioned indicators. After stress relief, the majority of physiological processes were reversible, as indicated by the effective recovery of pigment contents, photosynthetic rate, antioxidant enzyme activities, osmoregulatory substance contents, and O2- production. Antioxidant enzyme activities tended to increase after recovering from 12 days of combined stress, whereas they were still not effective in mitigating oxidative damage. High levels of O2- and malondialdehyde (MDA) and a low relative growth rate during the recovery confirmed the irreversible damage caused by combined heat and drought stress. ROC (receiver operating characteristic) analysis indicated that GR and SS could accurately detect individual heat and drought stress that wheat plants were suffering or had suffered (AUC = 0.812-0.965), while POD and Pro had greater potential for diagnosing combined heat and drought stress (AUC = 0.871-0.958). Physiological indicators of stress tolerance were closely related to the photosynthetic rate during the stress, particularly Pro and GR. Collectively, the physiological processes of plants are reversible within a certain range of stress. POD, GR, Pro, and SS play vital roles in identifying and resisting heat, drought, and combined stress, and the recovery of these indicators contributed to improving photosynthesis and thereby increasing wheat growth. Our research contributes to the understanding of the underlying physiological mechanisms of plants in response to combined heat and drought stress and after stress relief.

A novel circular RNA, circMAML3, promotes tumor progression of prostate cancer by regulating miR-665/MAPK8IP2 axis.

Many studies have now demonstrated that circRNAs are aberrantly expressed in cancer and are involved in the regulation of malignant tumor progression. However, the role of circMAML3 (hsa_circ_0125392) in prostate cancer has not been reported. circMAML3 was selected from public data through screening. The circMAML3 circular characterization was performed using Sanger sequencing, agarose gel electrophoresis assay, RNase R assay and actinomycin D assay. The expression of circMAML3 in prostate cancer tissues and cells was detected by qRT-PCR. In vivo and in vitro experiments were conducted to investigate the biological functions of circMAML3 in prostate cancer. Finally, the underlying mechanism of circMAML3 was revealed by qRT-PCR, luciferase reporter assay, miRNA Pulldown, RNA immunoprecipitation, western blotting, and rescue assay. Compared to normal prostate tissue and prostate epithelial cells, circMAML3 is highly expressed in prostate cancer tissues and cell lines. CircMAML3 overexpression promotes prostate cancer proliferation and metastasis, while knockdown of circMAML3 exerts the opposite effect. Mechanistically, circMAML3 promotes prostate cancer progression by upregulating MAPK8IP2 expression through sponge miR-665. Our research indicates that circMAML3 promotes prostate cancer progression through the circMAML3/miR-665/MAPK8IP2 axis. circMAML3 and MAPK8IP2 are upregulated in prostate cancer expression and play an oncogenic role, whereas miR-665 is downregulated in prostate cancer and plays an oncogenic role. Therefore, CircMAML3 may be a potential biomarker for prostate cancer diagnosis, treatment and prognosis.

SAPHO syndrome with Takayasu arteritis successfully treated with tofacitinib.

SAPHO syndrome is an autoinflammatory disease with a variety of clinical manifestations, which may be accompanied by other systemic inflammatory diseases in addition to the typical manifestations of common synovitis, acne, pustulosis, hyperostosis, and osteitis. Here, we report the first case of SAPHO syndrome combined with Takayasu arteritis.

Synergistic Photochemo Effects Based on Light-Activatable Dual Prodrug Nanoparticles for Effective Cancer Therapy.

Ferroptosis is identified as a novel type of cell death with distinct properties involved in physical conditions and various diseases, including cancers. It is considered that ferroptosis provides a promising therapeutic strategy for optimizing oncotherapy. Although erastin is an effective ferroptosis trigger, the potential of its clinical application is largely restricted by its poor water solubility and concomitant limitations. To address this issue, an innovative nanoplatform (PE@PTGA) that integrated protoporphyrin IX (PpIX) and erastin coated with amphiphilic polymers (PTGA) to evoke ferroptosis and apoptosis is constructed and exemplified using an orthotopic hepatocellular carcinoma (HCC) xenograft mouse model as a paradigm. The self-assembled nanoparticles can enter HCC cells and release PpIX and erastin. With light stimulation, PpIX exerts hyperthermia and reactive oxygen species to inhibit the proliferation of HCC cells. Besides, the accumulated reactive oxygen species (ROS) can further promote erastin-induced ferroptosis in HCC cells. In vitro and in vivo studies reveal that PE@PTGA synergistically inhibits tumor development by stimulating both ferroptosis- and apoptosis-related pathways. Moreover, PE@PTGA has low toxicity and satisfactory biocompatibility, suggesting its promising clinical benefit in cancer treatments.