Genetic characterizations of Cryptosporidium spp. from children with or without diarrhea in Wenzhou, China: high probability of zoonotic transmission.

BACKGROUND: Cryptosporidium is a highly pathogenic parasite responsible for diarrhea in children worldwide. Here, the epidemiological status and genetic characteristics of Cryptosporidium in children with or without diarrhea were investigated with tracking of potential sources in Wenzhou City, China. METHODS: A total of 1032 children were recruited, 684 of whom had diarrhea and 348 without, from Yuying Children's Hospital in Wenzhou, China. Samples of stool were collected from each participant, followed by extraction of DNA, genotyping, and molecular identification of Cryptosporidium species and subtypes. RESULTS: Twenty-two of the 1032 (2.1%) children were infected with Cryptosporidium spp. with 2.5% (17/684) and 1.4% (5/348) in diarrhoeic and asymptomatic children, respectively. Four Cryptosporidium species were identified, including C. parvum (68.2%; 15/22), C. felis (13.6%; 3/22), C. viatorum (9.1%; 2/22), and C. baileyi (9.1%; 2/22). Two C. parvum subtypes named IIdA19G1 (n = 14) and IInA10 (n = 1), and one each of C. felis (XIXa) and C. viatorum (XVaA3g) subtype was found as well. CONCLUSIONS: This is the first research that identified Cryptosporidium in children of Wenzhou, China, using PCR. Identification of zoonotic C. parvum, C. felis, C. viatorum, and their subtypes indicate potential cross-species transmission of Cryptosporidium between children and animals. Additionally, the presence of C. baileyi in children suggests that this species has a wider host range than previously believed and that it possesses the capacity to infect humans.

Physiological and biochemical mechanisms underlying the role of anthocyanin in acquired tolerance to salt stress in peanut (Arachis hypogaea L.).

Anthocyanin is an important pigment that prevents oxidative stress and mediates adaptation of plants to salt stress. Peanuts with dark red and black testa are rich in anthocyanin. However, correlation between salt tolerance and anthocyanin content in black and dark red testa peanuts is unknown. In this study, three peanut cultivars namely YZ9102 (pink testa), JHR1 (red testa) and JHB1 (black testa) were subjected to sodium chloride (NaCl) stress. The plant growth, ion uptake, anthocyanin accumulation, oxidation resistance and photosynthetic traits were comparatively analyzed. We observed that the plant height, leaf area and biomass under salt stress was highly inhibited in pink color testa (YZ9102) as compare to black color testa (JHB1). JHB1, a black testa colored peanut was identified as the most salt-tolerance cultivar, followed by red (JHR1) and pink(YZ9102). During salt stress, JHB1 exhibited significantly higher levels of anthocyanin and flavonoid accumulation compared to JHR1 and YZ9102, along with increased relative activities of antioxidant protection and photosynthetic efficiency. However, the K+/Na+ and Ca2+/Na+ were consistently decreased among three cultivars under salt stress, suggesting that the salt tolerance of black testa peanut may not be related to ion absorption. Therefore, we predicted that salt tolerance of JHB1 may be attributed to the accumulation of the anthocyanin and flavonoids, which activated antioxidant protection against the oxidative damage to maintain the higher photosynthetic efficiency and plant growth. These findings will be useful for improving salt tolerance of peanuts.

Molecular prevalence and subtype distribution of Blastocystis spp. among children who have diarrheia or are asymptomatic in Wenzhou, Zhejiang Province, China.

Blastocystis sp., a significant zoonotic parasite with a global distribution, was the focus of this study, which aimed to investigate its prevalence and genetic diversity among diarrheic and asymptomatic children in Wenzhou, China. We collected 1,032 fecal samples from Yuying Children's Hospital, Wenzhou, China, comprising 684 from children with diarrhea and 348 from asymptomatic children. Genomic DNA extracted from these samples was used to detect Blastocystis spp. by PCR, targeting the small subunit ribosomal RNA gene. Subsequently, a phylogenetic tree was constructed, applying the maximum likelihood method. Blastocystis spp. were detected in 67 (6.5%) of the fecal samples. The prevalence rate of Blastocystis spp. in diarrheic children (8.8%; 60/684) was significantly higher than that in asymptomatic children (2.0%; 7/348) (χ 2 = 17.3, p < 0.001). Sequence analysis of the SSU rRNA gene identified five known Blastocystis spp. subtypes, ST1 (n = 12), ST2 (n = 5), ST3 (n = 35), ST4 (n = 12), and ST7 (n = 3). ST1 and ST3 were present in both diarrheic and asymptomatic children, while ST2, ST4, and ST7 were exclusive to diarrheic children. Intra-subtype genetic polymorphisms were identified, comprising four variations in ST1 (ST1-1 to ST1-4), five in ST3 (ST3-1 to ST3-5), two in ST4 (ST4-1 and ST4-2), and two in ST7 (ST7-1 and ST7-2). Notably, ST1-2 to ST1-4, ST3-3 to ST3-5, and ST7-1 and ST7-2 represent newly identified variations. The composition and genetic characteristics of subtypes among children in this region suggest various sources of infection, including human-to-human and animal-to-human transmission.

Title: Prévalence moléculaire et distribution des sous-types de Blastocystis spp. parmi les enfants diarrhéiques et asymptomatiques à Wenzhou, Province du Zhejiang, Chine. Abstract: Blastocystis sp., un parasite zoonotique important avec une distribution mondiale, était au centre de cette étude, qui visait à étudier sa prévalence et sa diversité génétique parmi les enfants diarrhéiques et asymptomatiques de Wenzhou, en Chine. Nous avons collecté 1 032 échantillons fécaux à l'hôpital pour enfants Yuying de Wenzhou, en Chine, dont 684 provenant d'enfants souffrant de diarrhée et 348 d'enfants asymptomatiques. L'ADN génomique extrait de ces échantillons a été utilisé pour détecter Blastocystis sp. par PCR, ciblant le gène de la petite sous-unité de l'ARN ribosomal. Par la suite, un arbre phylogénétique a été construit, en appliquant la méthode du maximum de vraisemblance. Blastocystis sp. a été détecté dans 67 (6,5 %) des échantillons fécaux. Le taux de prévalence de Blastocystis spp. chez les enfants diarrhéiques (8,8 % ; 60 / 684) était significativement plus élevé que chez les enfants asymptomatiques (2,0 % ; 7 / 348) (χ2 = 17,3, p < 0,001). L'analyse de la séquence du gène de l'ARNr SSU a identifié cinq sous-types de Blastocystis spp., ST1 (n = 12), ST2 (n = 5), ST3 (n = 35), ST4 (n = 12) et ST7 (n = 3). Les sous-types ST1 et ST3 étaient présents chez les enfants diarrhéiques et asymptomatiques, tandis que ST2, ST4 et ST7 étaient exclusifs aux enfants diarrhéiques. Des polymorphismes génétiques intra-sous-types ont été identifiés, comprenant quatre variations dans ST1 (ST1-1 à ST1-4), cinq dans ST3 (ST3-1 à ST3-5), deux dans ST4 (ST4-1 et ST4-2) et deux dans ST7 (ST7-1 et ST7-2). Notamment, ST1-2 à ST1-4, ST3-3 à ST3-5, ST7-1 et ST7-2 représentent des variations nouvellement identifiées. La composition et les caractéristiques génétiques des sous-types chez les enfants de cette région suggèrent diverses sources d'infection, notamment la transmission interhumaine et animale.

Molecular mechanism of drought resistance in soybean roots revealed using physiological and multi-omics analyses.

Soybeans are one of the most cultivated crops worldwide and drought can seriously affect their growth and development. Many studies have elucidated the mechanisms through which soybean leaves respond to drought; however, little is known about these mechanisms in roots. We used two soybean varieties with different drought tolerances to study the morphological, physiological, and molecular response mechanisms of the root system to drought stress in seedlings. We found that drought stress led to a significant decrease in the root traits and an increase in antioxidant enzyme activity in the two varieties. Drought-resistant varieties accumulate large amounts of flavonoids and phenolic acids at the metabolic level, which causes variations in drought resistance. Additionally, differences in gene expression and drought-resistance pathways between the two varieties were clarified using transcriptome analysis. Through a multi-omics joint analysis, phenylpropanoid and isoflavonoid biosynthesis were identified as the core drought resistance pathways in soybean roots. Candidate genes and marker metabolites affecting drought resistance were identified. The phenylpropanoid pathway confers drought tolerance to roots by maintaining a high level of POD activity and mediates the biosynthesis of various secondary drought-resistant metabolites to resist drought stress. This study provides useful data for investigating plant root drought responses and offers theoretical support for plant breeding for drought resistance.

Quantification and Distribution of Thiols in Fermented Grains of Sauce-Aroma Baijiu Production Process.

Five volatile thiol compounds (methanethiol, ethanethiol, 2-mercapto-1-ethanol, 2-furfurylthiol, and 2-methyl-3-furanethiol) in fermented grains of sauce-aroma baijiu were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The samples were pre-treated using a modified QuEChERS method. 4,4'-Dithiodipyridine (DTDP) derivatization reaction improved the detectability and stability of volatile thiol compounds. From the end of the first round to the end of the seventh round of fermentation and different fermentation states from the fifth round of fermented grains of the sauce-aroma baijiu production process were analyzed. The results showed that the concentrations of methanethiol (67.64-205.37 µg/kg), ethanethiol (1.22-1.76 µg/kg), 2-furfurylthiol (0.51-3.03 µg/kg), and 2-methyl-3-furanthiol (1.70-12.74 µg/kg) were increased with the number of fermentation rounds. Methanethiol, 2-furfurylthiol, and 2-methyl-3-furanthiol increased during fermentation and distillation in the fifth round. Fermentation and distillation were important stages for their widespread production. After distillation, there were still a large number of volatile thiol compounds in the fermented grains. The thermal reaction was of great significance in the formation of these thiols.

[Reform and practice of Biopharmaceutical Technology Comprehensive Experiments in higher vocational colleges in the context of skills competition].

Comprehensive experiments course is a bridge for higher vocational students to integrate theoretical knowledge with production practice. The article introduces that our biological pharmacy department is committed to the principles of "promotion of teaching, learning and construction through skills competition so as to integrate education and training". By taking penicillin fermentation process as an example, reform has been made in several aspects including teaching objectives, teaching content and teaching methods. We integrate the practical operation of fermentation equipment with virtual simulation software to develop a two-way interactive course. By reducing the subjective dependence, the quantitative management and evaluation of fermentation process parameter control were put into place, which efficiently integrated the skills competition with practical teaching. Improved teaching performance has been achieved over recent years, which may facilitate the reform and practice of similar courses based on skills competition.

LncRNA EBLN3P attributes methotrexate resistance in osteosarcoma cells through miR-200a-3p/O-GlcNAc transferase pathway.

BACKGROUND: Osteosarcoma is highly malignant. The migration, invasion, and chemoresistance contribute to poor prognosis of osteosarcoma. Research reported that endogenous bornavirus-like nucleoprotein 3 pseudogene (EBLN3P) promotes the progression of osteosarcoma. METHODS: In this study, the expression of EBLN3P in osteosarcoma tissue with different methotrexate (MTX) treatment responses was measured. Osteosarcoma cell lines with MTX resistance were constructed, and bioinformatic analysis was performed to explore the potential involved targets and pathways. RESULTS: Higher EBLN3P was associated with MTX resistance. Downregulation of LncEBLN3P decreased the MTX resistance of osteosarcoma cells by sponging miR-200a-3p, an important microRNA that affects epithelial-mesenchymal transition (EMT). The decreased miR-200a-3p resulted in the upregulation of its target gene O-GlcNAc transferase (OGT), which in turn promoted the EMT process of osteosarcoma cells. Further analysis confirmed that the loss of OGT and over-expression of miR-200a-3p could partly abolish the MTX resistance induced by LncEBLN3P. CONCLUSION: LncEBLN3P is upregulated in osteosarcoma and increases the MTX resistance in osteosarcoma cells through downregulating miR-200a-3p, which in turn promoted the EMT process of osteosarcoma cells by increasing the OGT.

Pseudocatalytic Hydrogels with Intrinsic Antibacterial and Photothermal Activities for Local Treatment of Subcutaneous Abscesses and Breast Tumors.

The intimate relationship between bacteria and tumors has triggered a lot of activities in the development and design of bioactive materials to concurrently respond to antitumor and antibacterial demands. Herein, a pseudocatalytic hydrogel (AM-I@Agar) with intrinsic antibacterial and photothermal activities, synthesized by incorporating prefabricated amylose-iodine nanoparticles into low-melting-point agarose hydrogel, is explored as a bioactive agent for local treatment of subcutaneous abscesses and breast tumors. The AM-I@Agar hydrogel depicts the ability of pseudocatalytic O2 generation from H2 O2 to alleviate hypoxia. Meanwhile, the AM-I@Agar hydrogel exhibits temperature self-regulation features, beneficial for avoiding thermal injury during photothermal therapy owing to thermochromic properties. Upon local injection into a subcutaneous abscess, methicillin-resistant Staphylococcus aureus is effectively eliminated by the AM-I@Agar hydrogel, and complete skin recovery is achieved in 8 d, demonstrating much better antibacterial effects compared with penicillin, a small-molecule antibiotic. AM-I/5-FU@Agar hydrogel, obtained after loading 5-fluorouracil (5-FU), significantly inhibits tumors in both normal 4T1 tumor-bearing mice and MRSA-infected 4T1 tumor-bearing mice models via a synergistic photothermal-chemo effect, and shows treatment efficiency superior to that achieved with photothermal therapy or 5-FU alone. This work provides a concept for the design and development of bioactive agents for potential management of bacteria-associated cancer.

Deep eutectic solvents coupled with (NH4)3H6CoMo6O24 trigger aerobic oxidation of 5-hydroxymethylfurfural to 5-formyl-2-furancarboxylic acid.

An Anderson-type polyoxometalate (NH4)3H6CoMo6O24 in deep eutectic solvents exhibited outstanding catalytic performance for the selective aerobic oxidation of HMF to FFCA. It is potentially a promising and highly environmentally friendly approach for biomass conversion.

CEA-Ki-67- Pathologic Subtype: An Adjunct Factor for Refining Prognosis in Stage I Pulmonary Adenocarcinoma.

Objectives: The prognosis for stage I pulmonary adenocarcinoma is generally good. However, some patients with stage I pulmonary adenocarcinoma have an unexpectedly poor outcome. This warrants consideration of adjunct markers. In this study, we analyze carcinoembryonic antigen, Ki-67, and a pathologic subtype in combination for prognostic evaluation of stage I pulmonary adenocarcinoma. These factors were selected for study as they have been shown to be individually associated with prognosis in many studies. Methods: A total of 650 patients with stage I pulmonary adenocarcinoma were investigated retrospectively. Each patient was re-staged using standard TNM criteria. Carcinoembryonic antigen (CEA) values were obtained from preoperative blood samples, and Ki-67 was evaluated with tumor tissue immunohistochemistry. Patient clinicopathologic characteristics, survival status, and date of death were obtained from medical records and telephone follow-up. Results: CEA > 4.4 ng/ml, Ki-67 > 13%, and a solid-micropapillary tumor growth pattern were each independent adverse prognostic markers for 5-year disease specific survival in stage I pulmonary adenocarcinoma. However, in combination, these 3 factors yielded a prognostic value (designated "CEA-Ki-67-pathologic subtype" value). Stage I pulmonary adenocarcinoma of low-risk CEA-Ki-67-pathologic subtype (CKP) value show biologic behavior similar to TNM stage IA1 tumors, while stage I tumors of high-risk CKP value are similar in prognosis to TNM stage II. Conclusion: The CKP value may be used as an adjunct to the TNM classification, which may yield a more accurately defined prognosis for cases of stage I pulmonary adenocarcinoma. CKP value may identify patients at higher risk who may benefit from adjuvant chemotherapy. Conversely, lower risk CKP values may support avoidance of chemotherapy.

Sevoflurane preconditioning prevents acute renal injury caused by ischemia-reperfusion in mice via activation of the Nrf2 signaling pathway.

Oxidative stress, caused by renal ischemia reperfusion (IR)/hypoperfusion, is one of the main causes of acute kidney injury (AKI). Previous studies have demonstrated that sevoflurane (SEV) protects organs from the damage caused by oxidative stress. In the present study, mice were randomly assigned to a sham operation group (Sham), IR-vehicle group (IR+ vehicle), IR + SEV low-dose preconditioning group and an IR + SEV high-dose preconditioning group. The effect of SEV on nuclear factor E2-related factor 2 (Nrf2), a key regulatory protein of the endogenous antioxidant defense system and, consequently oxidative stress, inflammation and apoptosis-related factors, were all quantified using commercial kits or by western blotting. SEV preconditioning was demonstrated to ameliorate kidney injury as a result of decreased blood urine nitrogen and serum creatinine levels, activated Nrf2 expression in the kidney and decreased oxidative stress and inflammatory index levels an AKI mouse model. SEV preconditioning also protected injured kidney via the downregulation of caspase-3 protein expression levels. In addition, using the Nrf2 inhibitor, Brusatol, significantly abolished the SEV preconditioning renal protective effect. Using an in vitro HK-2 cell model of hypoxia/reoxygenation, it was also demonstrated that Nrf2 pathway activation was necessary for SEV to exert its beneficial effect for tubular cell injury caused by hypoxia/reoxygenation. These results indicated that SEV may protect against renal injury caused by IR via Nrf2 upregulation.

Relationship Between Leaflets and Root in Normal Aortic Valve Based on Computed Tomography Imaging: Implication for Aortic Valve Repair.

Objective: By assessing the normal dimensions and the relationship between the aortic root and leaflets in Chinese population, the objective of this three-dimensional computed tomography (3DCT)-based study was to establish a matching reference for leaflets and aortic root for aortic valve (AV) repair. Method: Electrocardiogram-gated multi-detector CT was performed on 168 Chinese participants with a normal aortic valve. Measurements of the aortic annuli and leaflets were obtained. The correlations between and the ratios of the specific root and leaflet measurements were analyzed. The references for the leaflet and root dimensions were suggested based on geometric height (gH) using a linear regression equation. The utility of the ratios was tested with CT images of 15 patients who underwent aortic valve repair. Result: The mean annulus diameter (AD), sino-tubular junction (STJ) diameter, geometric height (gH), effective height (eH), free margin length (FML), commissural height (ComH), inter-commissural distance (ICD), and coaptation height (CH) were 22.4 ± 1.7 mm, 27.3 ± 2, 0.4 mm, 15.5 ± 1.7 mm, 8.9 ± 1.2 mm, 32.0 ± 3.4 mm, 17.9 ± 1.9 mm, 23.1 ± 2.3 mm, and 3.1 ± 0.6 mm, respectively. The gH/AD, FML/ICD, and eH/ComH ratios were 0.69 ± 0.07, 1.38 ± 0.08, and 0.50 ± 0.07, respectively. The gH correlated with all other leaflet and root measurements (P < 0.01), whereas the FML demonstrated a better correlation with ICD compared with gH (R2 = 0.75, and R2 = 0.37, respectively). The FML/ICD and eH/ComH ratios might be used to assess leaflet-root mismatch and post-repair leaflet billowing. Conclusion: The normal aortic valve measurements based on 3DCT revealed a specific relationship between the root and leaflets; and this will guide the development of an objective method of aortic valve repair.

[A new phenolic acid ester from solid culture of Colletotrichum capsici, an endophytic fungus from Paeonia lactiflora].

A new phenolic acid ester, 4'-hydroxyphenylethyl 4,8(R)-dihydroxyphenylpropionate(1), was isolated from an endophytic fungus Colletotrichum capsici of Paeonia lactiflora roots, along with eight known phenolic derivatives, tyrosol(2), 2-(4-hydroxyphenyl) ethyl acetate(3), methyl p-hydroxyphenylacetate(4), methyl m-hydroxyphenylacetate(5), 4-(4-hydroxyphene-thoxy)-4-oxobutanoic acid(6), 4-hydroxyphenethyl methyl succinate(7), trichodenol B(8) and 4-hydroxyphenethyl 2-(4-hydroxyphenyl) acetate(9). Their structures were identified by a combination of high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) spectroscopy, ultraviolet(UV) spectroscopy and electronic circular dichroism(ECD) spectroscopy. Compounds 2-9 were isolated from this fungus for the first time.

Thermochromic Polyvinyl Alcohol-Iodine Hydrogels with Safe Threshold Temperature for Infectious Wound Healing.

Iodophor (povidone-iodine) has been widely used for antibacterial applications in the clinic. Yet, limited progress in the field of iodine-based bactericides has been achieved since the invention of iodophor. Herein, a blue polyvinyl alcohol-iodine (PAI) complex-based antibacterial hydrogel is explored as a new generation of biocompatible iodine-based bactericides. The obtained PAI hydrogel maintains laser triggered liquefaction, thermochromic, and photothermal features for highly efficient elimination of bacteria. In vitro antibacterial test reveals that the relative bacteria viabilities of Escherichia coli (E.coli) and methicillin-resistant Staphylococcus aureus (MRSA) incubated with PAI hydrogel are only 8% and 3.8%, respectively. Upon single injection of the PAI hydrogel, MRSA-infected open wounds can be efficiently healed in only 5 days, and the healing speed is further accelerated by laser irradiation due to the dynamic interaction between iodine and polyvinyl alcohol, causing up to ∼29% of wound area being closed on day 1. In addition, a safe threshold temperature of skin scald (∼45 °C) emerges for PAI hydrogels because of thermochromic properties, avoiding thermal injuries during irradiation. In addition, no observed toxicity or skin irritation is observed for the PAI hydrogel. This work expands the category of iodine-based bactericides for safe and controllable management of infected wounds.

Cryptobiosis-inspired assembly of "AND" logic gate platform for potential tumor-specific drug delivery.

Developing tumor-specific drug delivery systems with minimized off-target cargo leakage remains an enduring challenge. In this study, inspired from the natural cryptobiosis explored by certain organisms and stimuli-responsive polyphenol‒metal coordination chemistry, doxorubicin (DOX)-conjugated gelatin nanoparticles with protective shells formed by complex of tannic acid and FeIII (DG@TA-FeIII NPs) were successfully developed as an "AND" logic gate platform for tumor-targeted DOX delivery. Moreover, benefiting from the well-reported photothermal conversion ability of TA-FeIII complex, a synergistic tumor inhibition effect was confirmed by treating 4T1 tumor-bearing mice with DG@TA-FeIII NPs and localized near-infrared (NIR) laser irradiation. As a proof of concept study, this work present a simple strategy for developing "AND" logic gate platforms by coating enzyme-degradable drug conjugates with detachable polyphenol‒metal shells.

LINC01503/miR-342-3p facilitates malignancy in non-small-cell lung cancer cells via regulating LASP1.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the major types of lung cancer, which is a prevalent human disease all over the world. LncRNA LINC01503 is a super-enhancer-driven long non-coding RNA that is dysregulated in several types of human cancer. However, its role in NSCLC remains unknown. METHODS: Thirty NSCLC patients were recruited between April 2012 and April 2016. Luciferase reporter assay, qRT-PCR, Cell Counting Kit-8 (CCK-8), Transwell migration assay, RNA pull-down assay, western blotting, 5-ethynyl-29-deoxyuridine (EdU) assays, and flow cytometry were utilized to characterize the roles and relationships among LINC01503, miR-342-3p, and LASP1 in NSCLC. The transplanted mouse model was built to examine their biological functions in vivo. RESULTS: We demonstrated that the expression of lncRNA LINC01503 and LIM and SH3 domain protein 1 (LASP1) were upregulated and miR-342-3p was downregulated in NSCLC samples and cell lines. Functional experiments revealed that inhibiting the expression of LINC01503 or over-expression of miR-342-3p inhibited NSCLC growth and metastasis both in vitro and in vivo. In addition, LINC01503 could bind to miR-342-3p and affect the expression of LASP1. CONCLUSION: These results provide a comprehensive analysis of the roles of LINC01503 as a competing endogenous RNA (ceRNA) in NSCLC progression.

Immune Checkpoint Inhibitor Therapy Achieved Complete Response for Drug-Sensitive EGFR/ALK Mutation-Negative Metastatic Pulmonary Large-Cell Neuroendocrine Carcinoma with High Tumor Mutation Burden: A Case Report.

Large-cell neuroendocrine lung carcinoma (LCNELC) is classified into lung neuroendocrine tumors according to WHO 2015 classification guidelines and represents approximately 3% of all lung cancer. Because of the rarity of LCNELC, there is a lack of prospective studies guiding treatment. Here, we report a case of a patient with pT2aN2M0 stage IIIA LCNELC (drug-sensitive EGFR/ALK mutation-negative, PD-L1-negative but tumor mutation burden (TMB) high), who progressed rapidly after surgery but achieved a complete response to subsequent immune checkpoint inhibitor (ICI) therapy. The concentration of circulating tumor DNA (ctDNA) following the treatment course strongly reflects the response to ICI therapy. This report highlights the efficacy of ICI treatment in metastatic LCNELC patients with a high TMB and suggests that ctDNA analysis in detecting molecular residual disease may facilitate the personalization of ICI therapy.

Biodegradable Nickel Disulfide Nanozymes with GSH-Depleting Function for High-Efficiency Photothermal-Catalytic Antibacterial Therapy.

Bacterial infections caused by pathogens have always been a thorny issue that threatens human health, and there is urgent need to develop a new generation of antimicrobial nano-agents and treatments. Herein, biodegradable nickel disulfide (ND) nanozymes as excellent antibacterial agents that integrate excellent photothermal performance, nano-catalysis property, and glutathione (GSH)-depleting function have been successfully constructed. The ND nanozymes can effectively catalyze the decomposition of H2O2 to produce ⋅OH, and the hyperthermia of ND nanozymes generated by photothermal therapy (PTT) can further increase its catalytic activity, which provides rapid and effective bacterial killing effect compared with nano-catalytic treatment or PTT alone. Surprisingly, the ND nanozymes have the ability of GSH consumption, thus enhancing its sterilization effect. Moreover, the ND nanozymes are biodegradable nanomaterials that do not cause any significant toxicity in vivo. Collectively, the ND nanozymes with excellent photothermal performance, catalytic activity, and GSH-depleting function are used for high-efficiency sterilization.

Endogenous thrombopoietin promotes non-small-cell lung carcinoma cell proliferation and migration by regulating EGFR signalling.

Thrombopoietin (TPO) is a haematopoietic cytokine mainly produced by the liver and kidneys, which stimulates the production and maturation of megakaryocytes. In the past decade, numerous studies have investigated the effects of TPO outside the haematopoietic system; however, the role of TPO in the progression of solid cancer, particularly lung cancer, has not been well studied. Exogenous TPO does not affect non-small-cell lung cancer (NSCLC) cells as these cells show no or extremely low TPO receptor expression; therefore, in this study, we focused on endogenous TPO produced by NSCLC cells. Immunohistochemical analysis of 150 paired NSCLC and adjacent normal tissues indicated that TPO was highly expressed in NSCLC tissues and correlated with clinicopathological parameters including differentiation, P-TNM stage, lymph node metastasis and tumour size. Suppressing endogenous TPO by small interfering RNA inhibited the proliferation and migration of NSCLC cells. Moreover, TPO interacted with the EGFR protein and delayed ligand-induced EGFR degradation, thus enhancing EGFR signalling. Notably, overexpressing TPO in EGF-stimulated NSCLC cells facilitated cell proliferation and migration, whereas no obvious changes were observed without EGF stimulation. Our results suggest that endogenous TPO promotes tumorigenicity of NSCLC via regulating EGFR signalling and thus could be a therapeutic target for treating NSCLC.

Facile synthesis of monodisperse chromogenic amylose-iodine nanoparticles as an efficient broad-spectrum antibacterial agent.

The famous chromogenic reaction between starch and iodine has been widely used for chemical analysis since its first discovery in the year of 1814 while it is seldom utilized in biomedical applications. Inspired by their high iodine content and strong optical absorbance in the near infrared (NIR) region, monodisperse amylose-iodine nanoparticles (AM-I NPs), synthesized by simple mixing of amylose NPs and KI-I2 solutions, were explored as a new class of high-performance antibacterial agent. Benefiting from the broad-spectrum antibacterial property of iodine and photothermal effect of the amylose-iodine complex, the obtained AM-I NPs exhibited an excellent photothermal-enhanced sterilization effect for both Gram-negative Escherichia coli (E. coli) and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). For instance, upon incubation with AM-I NP suspensions (30 µg mL-1) plus NIR laser irradiation (808 nm, 1.33 W cm-2, 5 min), the relative survival rates of E. coli and MRSA were only 1.2% and 1.7%, respectively. In addition, the AM-I NPs depicted better biocompatibility in vitro than that of KI-I2 solution, indicating their safety for potential biomedical applications in vivo. This proof-of-concept study revealed the antibacterial applications of a traditional starch-iodine complex and is expected to provide insights into the design and development of efficient broad-spectrum antibacterial agents.