Genomic Epidemiology of SARS-CoV-2 in Guangdong Province, China.

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 infection and was first reported in central China in December 2019. Extensive molecular surveillance in Guangdong, China's most populous province, during early 2020 resulted in 1,388 reported RNA-positive cases from 1.6 million tests. In order to understand the molecular epidemiology and genetic diversity of SARS-CoV-2 in China, we generated 53 genomes from infected individuals in Guangdong using a combination of metagenomic sequencing and tiling amplicon approaches. Combined epidemiological and phylogenetic analyses indicate multiple independent introductions to Guangdong, although phylogenetic clustering is uncertain because of low virus genetic variation early in the pandemic. Our results illustrate how the timing, size, and duration of putative local transmission chains were constrained by national travel restrictions and by the province's large-scale intensive surveillance and intervention measures. Despite these successes, COVID-19 surveillance in Guangdong is still required, because the number of cases imported from other countries has increased.

Four and a half LIM domains 2 (FHL2) attenuates tumorigenesis of gastrointestinal stromal tumors (GISTs) by negatively regulating KIT signaling.

Gastrointestinal stromal tumors (GISTs) are predominately induced by KIT mutants. In this study, we found that four and a half LIM domains 2 (FHL2) was highly expressed in GISTs and KIT signaling dramatically increased FHL2 transcription while FHL2 inhibited KIT transcription. In addition, our results showed that FHL2 associated with KIT and increased the ubiquitination of both wild-type KIT and primary KIT mutants in GISTs, leading to decreased expression and activation of KIT although primary KIT mutants were less inhibited by FHL2 than wild-type KIT. In the animal experiments, loss of FHL2 expression in mice carrying germline KIT/V558A mutation which can develop GISTs resulted in increased tumor growth, but increased sensitivity of GISTs to imatinib treatment which is used as the first-line targeted therapy of GISTs, suggesting that FHL2 plays a role in the response of GISTs to KIT inhibitor. Unlike wild-type KIT and primary KIT mutants, we further found that FHL2 didn't alter the expression and activation of drug-resistant secondary KIT mutants. Taken together, our results indicated that FHL2 acts as the negative feedback of KIT signaling in GISTs while primary KIT mutants are less sensitive and secondary KIT mutants are resistant to the inhibition of FHL2.

Endothelial KCa3.1 and KCa2.3 Mediate S1P (Sphingosine-1-Phosphate)-Dependent Vasodilation and Blood Pressure Homeostasis.

BACKGROUND: S1P (sphingosine-1-phosphate) has been reported to possess vasodilatory properties, but the underlying pathways are largely unknown. METHODS: Isolated mouse mesenteric artery and endothelial cell models were used to determine S1P-induced vasodilation, intracellular calcium, membrane potentials, and calcium-activated potassium channels (KCa2.3 and KCa3.1 [endothelial small- and intermediate-conductance calcium-activated potassium channels]). Effect of deletion of endothelial S1PR1 (type 1 S1P receptor) on vasodilation and blood pressure was evaluated. RESULTS: Mesenteric arteries subjected to acute S1P stimulation displayed a dose-dependent vasodilation response, which was attenuated by blocking endothelial KCa2.3 or KCa3.1 channels. In cultured human umbilical vein endothelial cells, S1P stimulated immediate membrane potential hyperpolarization following activation of KCa2.3/KCa3.1 with elevated cytosolic Ca2+. Further, chronic S1P stimulation enhanced expression of KCa2.3 and KCa3.1 in human umbilical vein endothelial cells in dose- and time-dependent manners, which was abolished by disrupting either S1PR1-Ca2+ signaling or downstream Ca2+-activated calcineurin/NFAT (nuclear factor of activated T-cells) signaling. By combination of bioinformatics-based binding site prediction and chromatin immunoprecipitation assay, we revealed in human umbilical vein endothelial cells that chronic activation of S1P/S1PR1 promoted NFATc2 nuclear translocation and binding to promoter regions of KCa2.3 and KCa3.1 genes thus to upregulate transcription of these channels. Deletion of endothelial S1PR1 reduced expression of KCa2.3 and KCa3.1 in mesenteric arteries and exacerbated hypertension in mice with angiotensin II infusion. CONCLUSIONS: This study provides evidence for the mechanistic role of KCa2.3/KCa3.1-activated endothelium-dependent hyperpolarization in vasodilation and blood pressure homeostasis in response to S1P. This mechanistic demonstration would facilitate the development of new therapies for cardiovascular diseases associated with hypertension.

Cell-permeable PI3 kinase competitive peptide inhibits KIT mutant mediated tumorigenesis of gastrointestinal stromal tumor (GIST).

BACKGROUND: Mutations in the receptor tyrosine kinase KIT are the main cause of gastrointestinal stromal tumor (GIST), and the KIT mutants mediated PI3 kinase activation plays a key role in the tumorigenesis of GIST. In this study, we aimed to block PI3 kinase activation by cell-permeable peptide and investigate its possible application in the treatment of GIST. METHODS AND RESULTS: We designed cell-permeable peptides based on the binding domain of PI3 kinase subunit p85 to KIT or PI3 kinase subunit p110, respectively, in order to compete for the binding between p85 and KIT or p110 and therefore inhibit the activation of PI3 kinases mediated by KIT. The results showed that the peptide can penetrate the cells, and inhibit the activation of PI3 kinases, leading to reduced cell survival and cell proliferation mediated by KIT mutants in vitro. Treatment of mice carrying germline KIT/V558A mutation, which can develop GIST, with the peptide that can compete for the binding between p85 and p110, led to reduced tumorigenesis of GIST. The peptide can further enhance the inhibition of the tumor growth by imatinib which is used as the first line targeted therapy of GIST. CONCLUSIONS: Our results showed that cell-permeable PI3 kinase competitive peptide can inhibit KIT-mediated PI3 kinase activation and tumorigenesis of GIST, providing a rationale to further test the peptide in the treatment of GIST and even other tumors with over-activation of PI3 kinases.

Clinical analysis of a new multifunctional instrument set for gasless endoscopic thyroidectomy with two different approaches.

BACKGROUND: Following the rapid development of endoscopic thyroidectomy techniques, various surgical procedures have been developed (e.g., transoral, submandibular, areolar, axillary, retroauricular, and combined procedures), and each of these procedures has its own advantages. In recent years, gasless endoscopic thyroidectomy has emerged as a feasible procedure, and it has replaced traditional CO2 insufflation approaches because of advantages such as stable cavity construction, pollution reduction, resource saving, and risk reduction. However, each gasless procedure requires special instruments for cavity construction, and this results in enormous wastage of medical resources. In the present study, we introduced a set of instruments developed by our team. This set of instruments is designed to be compatible with the current gasless endoscopic thyroidectomy approaches, including transoral, submandibular, transareolar, transaxillary, retroauricular, combined, and lateral cervical lymph node dissection. Here, we introduced this set of instruments for two gasless endoscopic thyroidectomy procedures (transaxillary and transareolar). Following the incorporation of this set of instruments in regular clinical practice, it could be used for more gasless endoscopic thyroidectomy procedures in the future. OBJECTIVE: To investigate the feasibility, safety, and efficacy of the self-developed instruments for gasless endoscopic thyroidectomy in two different approaches. METHODS: A total of 180 patients diagnosed to have papillary thyroid carcinoma (PTC) between January 2020 and April 2022 were retrospectively investigated. The patients were assigned to a gasless transaxillary group (group A) and a gasless transareolar group (group B). The same gasless endoscopic-assisted instruments were used for both groups. The clinical characteristics, treatment results, and complications were compared between the two groups. RESULTS: All 180 patients were successfully operated. The extent of surgical resection in all patients was the same: "unilateral glandular lobectomy + isthmus combined with ipsilateral central zone lymph node dissection." There were 130 and 50 patients in group A and group B, respectively; one patient in the former group was converted to open surgery due to intraoperative bleeding. No significant difference was observed between the two groups in terms of gender, age, body mass index (BMI), education level, and proportion of concomitant Hashimoto's thyroiditis (P > 0.05). The establishment of cavity time was significantly longer in group A than in group B (35.62 ± 5.07 min vs. 17.46 ± 2.55 min, P < 0.01). The number of lymph nodes cleared was slightly less in group A than in group B (4.06 ± 2.93 vs. 4.52 ± 2.38, P = 0.07). Moreover, the two groups showed no significant differences (P > 0.05) in the total operative time (145.54 ± 45.11 min vs. 143.06 ± 46.70 min), tumor size (0.68 ± 0.46 cm vs. 0.71 ± 0.49 cm), postoperative hospital stay (4.08 ± 1.48 days vs. 3.72 ± 1.07 days), vocal cord paralysis [4 (3.1%) vs. 2 (4%)], postoperative swallowing discomfort [24 (18.5%) vs. 5 (10%)], and postoperative recurrence and satisfaction scores (3.27 ± 1.52 vs. 3.28 ± 1.53). CONCLUSION: Although the two approaches of gasless endoscopic surgery have different operative paths and different time periods for cavity construction, both approaches are similar in terms of the principle of cavity construction, safe and reliable postoperative efficacy, and good cosmetic effect. Therefore, the same set of instruments can be used to complete the surgery in both approaches, thus saving medical resources and facilitating the popularization of this technology.

YAP-galectin-3 signaling mediates endothelial dysfunction in angiotensin II-induced hypertension in mice.

BACKGROUND: Vascular endothelial dysfunction is regarded as an early event of hypertension. Galectin-3 (Gal-3) is known to participate in various pathological processes. Whilst previous studies showed that inhibition of Gal-3 effectively ameliorates angiotensin II (Ang II)-induced atherosclerosis or hypertension, it remains unclear whether Ang II regulates Gal-3 expression and actions in vascular endothelium. METHODS: Using techniques of molecular biology and myograph, we investigated Ang II-mediated changes in Gal-3 expression and activity in thoracic aortas and mesenteric arteries from wild-type and Gal-3 gene deleted (Gal-3-/-) mice and cultured endothelial cells. RESULTS: The serum level of Gal-3 was significantly higher in hypertensive patients or in mice with chronic Ang II-infusion. Ang II infusion to wild-type mice enhanced Gal-3 expression in the aortic and mesenteric arteries, elevated systolic blood pressure and impaired endothelium-dependent relaxation of the thoracic aortas and mesenteric arteries, changes that were abolished in Gal-3-/- mice. In human umbilical vein endothelial cells, Ang II significantly upregulated Gal-3 expression by promoting nuclear localization of Yes-associated protein (YAP) and its interaction with transcription factor Tead1 with enhanced YAP/Tead1 binding to Gal-3 gene promoter region. Furthermore, Gal-3 deletion augmented the bioavailability of nitric oxide, suppressed oxidative stress, and alleviated inflammation in the thoracic aorta of Ang II-infused mice or endothelial cells exposed to Ang II. CONCLUSIONS: Our results demonstrate for the first time that Ang II upregulates Gal-3 expression via increment in YAP nuclear localization in vascular endothelium, and that Gal-3 mediates endothelial dysfunction contributing to the development of hypertension.

Job preferences of master of public health students in China: a discrete choice experiment.

BACKGROUND: The shortage of public health personnel and the uneven distribution between urban and rural areas are thorny issues in China. Master of public health (MPH) is an integral part of public health human resources in the future, and it is of far-reaching significance to discuss their work preferences. The present study wants to investigate the job preference of MPH, understand the relative importance of different job attributes, and then put forward targeted incentive measures. METHODS: Discrete choice experiment (DCE) was used to evaluate the job preference of MPHs in two medical colleges in Liaoning Province. Attributes include employment location, bianzhi, working environment, career development prospects, work value and monthly income. Thirty-six choice sets were developed using a fractional factorial design. Mixed logit models were used to analysis the DCE data. RESULTS: The final sample comprised 327 MPHs. All the attributes and levels included in the study are statistically significant. Monthly income is the most important factor for MPHs. For non-economic factors, they value career development prospects most, followed by the employment location. Respondents' preferences are heterogeneous and influenced by individual characteristics. Subgroup analysis showed that respondents from different family backgrounds have different job preferences. Policy simulation suggested that respondents were most sensitive to a salary increase, and the combination of several non-economic factors can also achieve the same effect. CONCLUSIONS: Economic factors and non-economic factors significantly affect the job preference of MPHs. To alleviate the shortage and uneven distribution of public health personnel, more effective policy intervention should comprehensively consider the incentive measures of the work itself and pay attention to the individual characteristics and family backgrounds of the target object.

[Development and Clinical Application of Multifunctional Inflation-Free Lumpectomy Aid].

To investigate the value of self-developed air-free laparoscopic auxiliary instruments in the clinical application of thyroid diseases. The clinical data of 70 transaxillary and 45 transareolar air-free laparoscopic surgeries for thyroid cancer and 40 conventional open surgeries were retrospectively compared. The transaxillary and transareolar laparoscopic groups had significantly longer operative times than the open group, while the postoperative satisfaction was higher in the endoscopic group than in the open group. This set of instruments has advantage of novel design, scientific structure, safe application. It can be compatible with a variety of thyroid and breast air-free laparoscopic procedures, which can promote the development and popularization of laparoscopic technology.

Bioparameter-directed nanoformulations as MRI CAs enable the specific visualization of hypoxic tumour.

A malignant tumour has hypoxic cells of varying degrees. The more severe the hypoxic degree, the more difficult the prognosis of the tumour and the higher the recurrence rate. Therefore, tumour hypoxia imaging is crucial. Magnetic resonance imaging (MRI) shows its strength in high resolution, depth of penetration and noninvasiveness. However, it needs more excellent contrast agents (CAs) to combat the complex tumour microenvironment (TME) and increased targeting of tumours to enhance clinical safety. Many research studies have focused on developing hypoxia-responsive MRI CAs that take advantage of the unique characteristics of hypoxic tumours. The low oxygen pressure, acidic TME, and up-regulated redox molecule levels found in hypoxic tumours serve as biological stimuli for nanoformulations that can accurately image the hypoxic region. This review highlights the importance of developing bioparameter-directed nanoformulations as MRI CAs for accurate tumour diagnosis. The design strategies and mechanisms of tumour-hypoxia imaging with nanoformulations are exemplified, with a focus on pH-responsiveness, redox-responsiveness, and p(O2)-responsiveness. The promising future of bioparameter-responsive nanoformulations for accurate tumour diagnosis and personalised cancer treatment is discussed.

SPRY4 inhibits and sensitizes the primary KIT mutants in gastrointestinal stromal tumors (GISTs) to imatinib.

BACKGROUND: KIT is frequently mutated in gastrointestinal stromal tumors (GISTs), and the treatment of GISTs largely relies on targeting KIT currently. In this study, we aimed to investigate the role of sprouty RTK signaling antagonist 4 (SPRY4) in GISTs and related mechanisms. METHODS: Ba/F3 cells and GIST-T1 cell were used as cell models, and mice carrying germline KIT/V558A mutation were used as animal model. Gene expression was examined by qRT-PCR and western blot. Protein association was examined by immunoprecipitation. RESULTS: Our study revealed that KIT increased the expression of SPRY4 in GISTs. SPRY4 was found to bind to both wild-type KIT and primary KIT mutants in GISTs, and inhibited KIT expression and activation, leading to decreased cell survival and proliferation mediated by KIT. We also observed that inhibition of SPRY4 expression in KITV558A/WT mice led to increased tumorigenesis of GISTs in vivo. Moreover, our results demonstrated that SPRY4 enhanced the inhibitory effect of imatinib on the activation of primary KIT mutants, as well as on cell proliferation and survival mediated by the primary KIT mutants. However, in contrast to this, SPRY4 did not affect the expression and activation of drug-resistant secondary KIT mutants, nor did it affect the sensitivity of secondary KIT mutants to imatinib. These findings suggested that secondary KIT mutants regulate a different downstream signaling cascade than primary KIT mutants. CONCLUSIONS: Our results suggested that SPRY4 acts as negative feedback of primary KIT mutants in GISTs by inhibiting KIT expression and activation. It can increase the sensitivity of primary KIT mutants to imatinib. In contrast, secondary KIT mutants are resistant to the inhibition of SPRY4.

Detection and Segmentation of Breast Masses Based on Multi-Layer Feature Fusion.

In breast mass detection, there are many different sizes of masses in the image. However, when the existing target detection model is directly used to detect the breast mass, it is easy to appear the phenomenon of misdetection and missed detection. Therefore, in order to improve the detection accuracy of breast masses, this paper proposed a target detection model D-Mask R-CNN based on Mask R-CNN, which is suitable for breast masses detection. Firstly, this paper improved the internal structure of FPN, and modified the lateral connection mode in the original FPN structure to dense connection. Secondly, modified the size of the anchor of RPN to improve the location accuracy of breast masses. Finally, Soft-NMS was used to replace the NMS in the original model to reduce the possibility that the correct prediction results may be eliminated during the NMS process. This paper used the CBIS-DDSM dataset for all experiments. The results showed that the mAP value of the improved model for detecting breast masses reached 0.66 in the test set, which was 0.05 higher than that of the original Mask R-CNN.

Giant unilateral electric-field control of magnetic anisotropy in MgO/Rh2CoSb heterojunctions.

A large voltage-controlled magnetic anisotropy (VCMA) effect is highly desirable for applications of voltage-torque magnetic random access memory. In this work, the dependence of magnetic anisotropy (MA) on the electric field in a MgO-based heterojunction consisting of a new Heusler alloy, Rh2CoSb, is studied using first-principles calculations. We find that the Rh-terminated MgO/Rh2CoSb heterojunction has a perpendicular MA and a giant VCMA coefficient of 7024 fJ V-1 m-1. Furthermore, the VCMA coefficient shows a characteristic of dependence on the electric-field direction. The origins of these behaviors are elucidated by orbital-resolved MA and second-order perturbation theoretical analysis. As the spin-down states of the in-plane orbital, dxy, are close to the Fermi level, the shift of these states induced by the electric field gives rise to significant changes of magnetic anisotropy energy, which is mainly responsible for the giant VCMA effect.

Impact of alexithymia on suicidal ideation among patients with ovarian cancer: a moderated mediation model of self-perceived burden and general self-efficacy.

PURPOSE: Suicidal ideation (SI) and alexithymia are common psychological problems among patients with cancer. Studying how alexithymia predicts SI is helpful for its intervention and prevention strategies. The present study aimed to investigate whether self-perceived burden (SPB) mediates the impact of alexithymia on SI and if general self-efficacy moderates the associations of alexithymia with SPB and SI. METHODS: To measure SI, alexithymia, SPB, and general self-efficacy, 200 patients with ovarian cancer at all stages regardless of the type of treatment completed the Chinese version of the Self-Rating Idea of Suicide Scale, Toronto Alexithymia Scale, Self-Perceived Burden Scale, and General Self-Efficacy Scale in a cross-sectional study. The PROCESS macro for SPSS v4.0 procedure was applied to perform moderated mediation analysis. RESULTS: SPB significantly mediated the positive impact of alexithymia on SI (a×b = 0.082, 95% confidence interval [CI]: 0.026, 0.157). General self-efficacy significantly moderated the positive association between alexithymia and SPB (ß = -0.227, P < 0.001). The mediating role of SPB was gradually reduced as general self-efficacy grew (low: 0.087, 95% CI: 0.010, 0.190; medium: 0.049, 95% CI: 0.006, 0.108; high: 0.010, 95% CI: -0.014, 0.046). Thus, a moderated mediation model involving SPB and general self-efficacy for explaining how alexithymia causes SI was supported. CONCLUSION: Alexithymia could cause SI by inducing SPB among patients with ovarian cancer. General self-efficacy could attenuate the association between alexithymia and SPB. Interventions aimed at reducing SPB and enhancing general self-efficacy could reduce SI by partially preventing and attenuating the impact of alexithymia.

Exploring the reciprocal relationship between activities of daily living disability and depressive symptoms among middle-aged and older Chinese people: a four-wave, cross-lagged model.

BACKGROUND: Early studies have shown a relationship between activities of daily living (ADL) disability and depressive symptoms in older people. However, discussions on the direction of this relationship are insufficient. The study's objective was to assess the reciprocal relationship between ADL disability and depressive symptoms among middle-aged and older Chinese people. METHOD: Data was collected in four waves of a nationwide survey, the China Health and Retirement Longitudinal Study (CHARLS), which was carried out in 2011, 2013, 2015, and 2018. In total, this study included 4,124 participants aged ≥ 45 years at baseline. A summing score of the eleven items for basic activities of daily living (BADL) and instrumental activities of daily living (IADL) was calculated to indicate the degree of ADL disability. The 10-item Centre for Epidemiological Studies Depression Scale (CESD-10) was adopted to measure depressive symptoms. The reciprocal relationship between ADL disability and depressive symptoms was tested by cross-lagged models. RESULT: At baseline, 911 (22.1%) participants were classified as having difficulties with ADL, and the prevalence of depressive symptoms was 34.4% (1,418). Among middle-aged and older people in China, there was a significant reciprocal and longitudinal relationship between ADL disability and depressive symptoms. People who had difficulty with ADL faced a higher risk of depressive symptoms, and those who suffered from depressive symptoms were accompanied by an increase in ADL disability in the following years. The subgroup analysis on age also showed that ADL disability was reciprocally and longitudinally related to depressive symptoms. However, only women showed similar results in the subgroup analysis on gender. CONCLUSION: This study shows that ADL disability is bi-directionally related to depressive symptoms in middle-aged and older Chinese people over time. The results suggest we should identify ADL disability and bad psychological conditions in time to prevent subsequent mutual damage among middle-aged and older Chinese people, a vulnerable group rising in the future.

MiR-19a-3p Promotes Aerobic Glycolysis in Ovarian Cancer Cells via IGFBP3/PI3K/AKT Pathway.

Aerobic glycolysis is a prominent feature of cancer. Here, we reported that miR-19a-3p promotes aerobic glycolysis in ovarian cancer cells SKVO3 and ES-2 by increased production of ATP, lactic acid, extracellular acidification (ECAR), and increased expression of PKM2, LDHA, GLUT1 and GLUT3. Further study showed that over-expression of IGFBP3, the target of miR-19a-3p, decreases aerobic glycolysis in ovarian cancer cells, while knockdown of IGFBP3 expression increases aerobic glycolysis. The rescue assay suggested that miR-19a-3p promotes aerobic glycolysis in ovarian cancer cells through targeting IGFBP3. Moreover, over-expression of miR-19a-3p or silencing of IGFBP3 expression promoted activation of AKT, which is important for aerobic glycolysis in cancer cells, indicating that miR-19a-3p promotes aerobic glycolysis in ovarian cancer cells through the IGFBP3/PI3K/AKT pathway. This suggests that miR-19a-3p and IGFBP3 may serve as potential treatment targets of ovarian cancer.

Forensic characteristics and genetic substructure analysis of the Handan Han population, Northern China.

We analysed the forensic characteristics and substructure of the Handan Han population based on 36 Y-STR (short tandem repeat) and Y-SNP (single nucleotide polymorphism) markers. The two most dominant haplogroups in Handan Han, O2a2b1a1a1-F8 (17.95%) and O2a2b1a2a1a (21.51%), and their abundant downstream branches, reflected the strong expansion of the precursor of the Hans in Handan. The present results enrich the forensic database and explore the genetic relationships between Handan Han and other neighbouring and/or linguistically close populations, which suggests that the current concise overview of the Han intricate substructure remains oversimplified.

[Features of Production Process and Risk Prevention and Control Points of Corona Virus Disease 2019 (2019-nCoV) Antigen Detection Reagent (Colloidal Gold Method)].

Corona Virus Disease 2019 (2019-nCoV) antigen detection reagent (colloidal gold method) has been applied to people who go to basic medical and health institutions for medical treatment and have respiratory tract, fever and other symptoms within 5 days, isolate observers, community residents who need antigen self-testing. The wide application of the reagent can effectively shorten the detection time, reduce the detection cost and time cost, and alleviate the pressure of nucleic acid detection. The article details the structural components, testing principles, production process and key risk points of the new coronavirus antigen test reagents, with the aim of providing a reference for the development of relevant work specifications for manufacturers, the organization of safe production and the verification and supervision of regulatory authorities.

A zinc finger protein SlSZP1 protects SlSTOP1 from SlRAE1-mediated degradation to modulate aluminum resistance.

In acidic soils, aluminum (Al) toxicity is the main factor inhibiting plant root development and reducing crops yield. STOP1 (SENSITIVE TO PROTON RHIZOTOXICITY 1) was a critical factor in detoxifying Al stress. Under Al stress, STOP1 expression was not induced, although STOP1 protein accumulated, even in the presence of RAE1 (STOP1 DEGRADATION E3-LIGASE). How the Al stress triggers and stabilises the accumulation of STOP1 is still unknown. Here, we characterised SlSTOP1-interacting zinc finger protein (SlSZP1) using a yeast-two-hybrid screening, and generated slstop1, slszp1 and slstop1/slszp1 knockout mutants using clustered regularly interspaced short palindromic repeats (CRISPR) in tomato. SlSZP1 is induced by Al stress but it is not regulated by SlSTOP1. The slstop1, slszp1 and slstop1/slszp1 knockout mutants exhibited hypersensitivity to Al stress. The expression of SlSTOP1-targeted genes, such as SlRAE1 and SlASR2 (ALUMINUM SENSITIVE), was inhibited in both slstop1 and slszp1 mutants, but not directly regulated by SlSZP1. Furthermore, the degradation of SlSTOP1 by SlRAE1 was prevented by SlSZP1. Al stress increased the accumulation of SlSTOP1 in wild-type (WT) but not in slszp1 mutants. The overexpression of either SlSTOP1 or SlSZP1 did not enhance plant Al resistance. Altogether, our results show that SlSZP1 is an important factor for protecting SlSTOP1 from SlRAE1-mediated degradation.

Pioneering Iodine-125-Labeled Nanoscale Covalent Organic Frameworks for Brachytherapy.

Brachytherapy has been clinically used for the treatment of malignant solid tumors. However, the classic therapeutic radioactive 125I seed must be surgically implanted directly into tumors. To avoid the surgery and prevent irrational radioactive distribution, radioiodine-loaded nanomaterials are ever-developing for brachytherapy. Hence, it is still a notable challenge to obtain an advanced material that simultaneously incorporates features of high radiolabeling rate, short labeling time, good radiolabeling stability, and long tumor retention time. Covalent organic frameworks (COFs), which are crystalline polymers with ordered pores, are widely applied in guest delivery of drugs based on their high porosity and modifiable skeleton. Herein, we developed a functionalized nanoscale PEG-COF-Ag material, which could rapidly capture radioiodine reaching a 94% radiolabeling yield in 30 s. In addition, more than 95% 125I was maintained after 24 h in PBS (phosphate-buffered saline) as well as in serum and over 90% for nearly 1 week. PEG-COF-Ag-125I (125I-COF) demonstrated excellent cancer cell killing performance in vitro, and further experiments in vivo revealed a long tumor retention time and effective tumor treatment during the radiotherapy. The results indicate that radioiodine-labeled PEG-COF-Ag could be potentially applied in brachytherapy with a promising therapeutic effect.

A One-pot-synthesized Double-layered Anticoagulant Hydrogel Tube.

Extracorporeal membrane oxygenation(ECMO) has emerged as a viable treatment in severe cases of acute respiratory distress syndrome, acute respiratory failure, and adult respiratory distress syndrome. However, thromboembolic events stemming from the use of ECMO devices results in significant morbidity and mortality rates; the inner surface of the ECMO tubing comes into contact with the blood and can readily initiate coagulation. In addition, the tubing needs to be continually replaced due to thromboses on the inner tube wall, which not only increases the risk of infection but also the economic burden. Despite considerable effort, a surface modification strategy that effectively addresses these challenges has not yet been realized. In this study, we developed an integrated hollow core-shell-shell hydrogel tube of gelatin/alginate/acrylamide-bacterial nanocellulose(GAA) that meets the anticoagulant requirements for the inner tubing layer as well as the highly elastic soft material needed for the outer layer. Using static blood from healthy volunteers, we confirmed that the platelets or coagulation is not stimulated by the GAA tubing. Importantly, experiments with dynamic blood also demonstrated that the inner layer of the tubing does not elicit blood clotting. The one-pot-synthesized process may provide guidance for the design of anticoagulation tubes used clinically. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at 10.1007/s40242-021-1267-3.