Combined prevention and treatment measures are essential to control nosocomial infections during the COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus-2 is a highly contagious positive-sense, single-stranded RNA virus that has rapidly spread worldwide. As of December 17, 2023, 772838745 confirmed cases including 6988679 deaths have been reported globally. This virus primarily spreads through droplets, airborne transmission, and direct contact. Hospitals harbor a substantial number of confirmed coronavirus disease 2019 (COVID-19) patients and asymptomatic carriers, accompanied by high population density and a larger susceptible population. These factors serve as potential triggers for nosocomial infections, posing a threat during the COVID-19 pandemic. Nosocomial infections occur to varying degrees across different countries worldwide, emphasizing the urgent need for a practical approach to prevent and control the intra-hospital spread of COVID-19. This study primarily concentrated on a novel strategy combining preventive measures with treatment for combating COVID-19 nosocomial infections. It suggests preventive methods, such as vaccination, disinfection, and training of heathcare personnel to curb viral infections. Additionally, it explored therapeutic strategies targeting cellular inflammatory factors and certain new medications for COVID-19 patients. These methods hold promise in rapidly and effectively preventing and controlling nosocomial infections during the COVID-19 pandemic and provide a reliable reference for adopting preventive measures in the future pandemic.

Impact of COVID-19 pandemic on routine childhood vaccinations.

Routine pediatric vaccination is one of the most effective public health inter-ventions for the control of a number of fatal diseases. However, during the coronavirus disease 2019 pandemic, routine pediatric vaccination rates were severely affected by disruptions of health services and vaccine confidence issues. Governments and the United Nations have taken measures to re-establish routine pediatric vaccination, while additional efforts are needed to catch up and develop plans to ensure routine vaccination services for the future pandemics.

Precise Synthesis of Diastereomers of Spiro-oxindole Derivatives through Dynamic Covalent Transformation.

In this study, [1+2+2] cyclization of tryptamine-derived isocyanides with 3-ylideneoxindoles was systematically investigated. A series of structurally complex spiro-oxindole derivatives were obtained. Characteristic dynamic covalent chemistry was observed and confirmed by experiments and density functional theory calculation. Through the regulation of the solvent, temperature, and time, the precise and stereodivergent synthesis of spiro-oxindoles was achieved.

Opsin mutants alter host plant selection by color vision in the nocturnal invasive pest Tuta absoluta.

In insects, vision is crucial in finding host plants, but its role in nocturnal insects is largely unknown. Vision involves responses to specific spectra of photon wavelengths and opsins plays an important role in this process. Long-wavelength sensitive opsin (LW opsin) and blue-sensitive opsin (BL opsin) are main visual opsin proteins and play important in behavior regulation.We used CRISPR/Cas9 technology to mutate the long-wavelength-sensitive and blue wavelength-sensitive genes and explored the role of vision in the nocturnal invasive pest Tuta absoluta. Light wave experiments revealed that LW2(-/-) and BL(-/-) mutants showed abnormal wavelength tropism. Both LW2 and BL mutations affected the preference of T. absoluta for the green environment. Mutations in LW2 and BL are necessary to inhibit visual attraction. The elimination of LW2 and BL affected the preference of leaf moths for green plants, and mutations in both induced a preference in moths for white plants. Behavioral changes resulting from LW2(-/-) and BL(-/-) mutants were not affected by sense of smell, further supporting the regulatory role of vision in insect behavior. To the best of our knowledge, this is the first study to reveal that vision, not smell, plays an important role in the host-seeking behavior of nocturnal insects at night, of which LW2 and BL opsins are key regulatory factors. These study findings will drive the development of the "vision-ecology" theory.

SMAD4 endows TGF-ß1-induced highly invasive tumor cells with ferroptosis vulnerability in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy prone to recurrence and metastasis. Studies show that tumor cells with increased invasive and metastatic potential are more likely to undergo ferroptosis. SMAD4 is a critical molecule in the transforming growth factor ß (TGF-ß) pathway, which affects the TGF-ß-induced epithelial-mesenchymal transition (EMT) status. SMAD4 loss is observed in more than half of patients with PDAC. In this study, we investigated whether SMAD4-positive PDAC cells were prone to ferroptosis because of their high invasiveness. We showed that SMAD4 status almost determined the orientation of transforming growth factor ß1 (TGF-ß1)-induced EMT via the SMAD4-dependent canonical pathway in PDAC, which altered ferroptosis vulnerability. We identified glutathione peroxidase 4 (GPX4), which inhibited ferroptosis, as a SMAD4 down-regulated gene by RNA sequencing. We found that SMAD4 bound to the promoter of GPX4 and decreased GPX4 transcription in PDAC. Furthermore, TGF-ß1-induced high invasiveness enhanced sensitivity of SMAD4-positive organoids and pancreas xenograft models to the ferroptosis inducer RAS-selective lethal 3 (RSL3). Moreover, SMAD4 enhanced the cytotoxic effect of gemcitabine combined with RSL3 in highly invasive PDAC cells. This study provides new ideas for the treatment of PDAC, especially SMAD4-positive PDAC.

Palladium-catalyzed carbomonofluoromethylation of unactivated alkenes: rapid access to γ-monofluoromethyl carboxylic acid derivatives.

Herein, we report a palladium-catalyzed regioselective carbomonofluoromethylation of unactivated alkenes. The reaction uses easily available fluorobis(phenylsulfonyl)methane (FBSM) as a fluoromethylating reagent, and proceeds smoothly with a wide variety of carbon electrophiles, including (hetero)aryl iodides, styrenyl iodides and TIPSBr. A range of remote γ-CH2F/CD2F carboxylic acid derivatives were constructed rapidly after a simple reductive desulfonylation step. The reaction features high regioselectivity, mild and simple reaction conditions and a broad substrate scope, and is easy to scale up.

Coupling-Spirocyclization Cascade of Tryptamine-Derived Isocyanides with Iodonium Ylides and Despirocyclization Reactions.

A cobalt(II)-catalyzed coupling-cyclization cascade reaction between tryptamine-derived isocyanides and iodonium ylides is investigated, which allowed for the synthesis of different types of spiroindoline compounds by variation of substituents at the N1- and C2-positions in the indole skeleton. More interesting is that the spiroindoline products could undergo despirocyclization in the presence of amines, enabling efficient construction of enamine compounds.

A Novel Approach to α-Arylacetonitrile Skeletons via para-Selective Alkylation of Protected Anilines.

A ruthenium-catalyzed para-selective alkylation of protected anilines to construct α-arylacetonitrile skeletons has been reported. We firstly disclosed the ethyl 2-bromo-2-cyanopropanoate was an effective alkylating reagent in ruthenmuim-catalyzed remote-selective C-H functionalization. A wide variety of α-arylacetonitrile skeletons can be directly obtained with moderate to good yields. Importantly, the products contain both nitrile and ester groups guaranteeing its direct transformation into other useful synthetic units, indicating the synthetic importance of this method.

Synthesis of Azoxy Compounds: from Copper Compounds to Mesoporous Silica-Encaged Ultrasmall Copper Catalysts.

Azoxy compounds have aroused extensive attention due to their unique biological activities, but the chemical synthesis of these compounds often suffers from limitations due to their requirement for stoichiometric oxidants, high costs, and restricted substrate range. Herein, a series of azoxy compounds were constructed via facile coupling reactions by using cost-effective N-methoxyformamide and nitroso compounds over Cu-based catalysts, affording high product yields with excellent tolerance of functional groups. Significantly, the mesoporous silica nanosphere-encapsulated ultrasmall Cu (Cu@MSN) catalyst was developed via a one-pot synthetic method and first used for the synthesis of azoxy compounds. As compared with copper salt catalysts, the Cu@MSN catalyst exhibited remarkably enhanced catalytic activity and superior recycling stability. Such a Cu@MSN catalyst overcame the inherent drawbacks of low activity, fast deactivation, and difficult recycling of traditional metal salt catalysts in organic reactions. This work provides a green and efficient method for the construction of azoxy compounds and also creates new prospects for the application of nanoporous materials confined metal catalysts in organic synthesis.

NBS-induced intramolecular annulation reactions for the divergent synthesis of fused- and spirocyclic indolines.

An NBS-induced intramolecular annulation of 3-(1H-indol-3-yl)-N-alkoxypropanamide is described. The reactions proceed well and quickly under mild conditions with the help of a base. It was found that C2-substituents on the indole ring in 3-(1H-indol-3-yl)-N-alkoxypropanamide have a great influence upon the reaction. By using C2-methyl- and C2-phenyl-3-(1H-indol-3-yl)-N-alkoxypropanamide as templates, practical protocols for the divergent synthesis of fused- and spirocyclic indoline compounds were studied and established.

The Surgical and Therapeutic Activities of Non-Functional Pancreatic Neuroendocrine Tumors at a High-Volume Institution.

BACKGROUND: This study aimed to summarize the surgical and therapeutic activities of non-functional pancreatic neuroendocrine tumors (NF-PanNETs) and perform survival analyses of a 15-year single-institutional cohort of NF-PanNETs. METHODS: In total, 1001 patients with neuroendocrine neoplasms treated at Fudan University Shanghai Cancer Center were screened for inclusion, and 509 patients with NF-PanNETs from 2006 to 2020 were included. For time trend analyses, the 15-year study period was randomly divided into three periods. Survival analyses used the Kaplan-Meier method and Cox regression models. RESULTS: The total number of resected NF-PanNETs increased over the 15-year study period, from 5 resections in 2006 to 94 resections in 2020. A significant decrease in the tumor size was observed, from a mean of 4.0 cm to 3.3 cm, and to 3.0 cm in the most recent period (p = 0.006). Minimally invasive techniques gradually increased from 3.5% to 12.9%, and finally to 46.4% in the most recent period (p < 0.001). In non-metastatic and resected tumors, the tumor size (p < 0.001), positive lymph node (p < 0.001), adjuvant treatment (p = 0.048), and tumor grade (p < 0.001) were independent prognostic factors for recurrence-free survival (RFS). The microvascular invasion (p = 0.024) and tumor grade (p = 0.013) were independent prognostic factors for overall survival (OS). A malignant transformation from NET into neuroendocrine carcinoma was observed. CONCLUSIONS: An increasing number of NF-PanNETs resection and minimally invasive surgery was shown. In non-metastatic and resected tumors NF-PanNETs, tumor size, positive lymph node, adjuvant treatment, and tumor grade were independent predictors of RFS. Microvascular invasion and tumor grade were independent prognostic factors for OS.

A new glance at autophagolysosomal-dependent or -independent function of transcriptional factor EB in human cancer.

Autophagy-lysosome system plays a variety of roles in human cancers. In addition to being implicated in metabolism, it is also involved in tumor immunity, remodeling the tumor microenvironment, vascular proliferation, and promoting tumor progression and metastasis. Transcriptional factor EB (TFEB) is a major regulator of the autophagy-lysosomal system. With the in-depth studies on TFEB, researchers have found that it promotes various cancer phenotypes by regulating the autophagolysosomal system, and even in an autophagy-independent way. In this review, we summarize the recent findings about TFEB in various types of cancer (melanoma, pancreatic ductal adenocarcinoma, renal cell carcinoma, colorectal cancer, breast cancer, prostate cancer, ovarian cancer and lung cancer), and shed some light on the mechanisms by which it may serve as a potential target for cancer treatment.

Lactate-induced protein lactylation: A bridge between epigenetics and metabolic reprogramming in cancer.

Lactate is not only an endpoint of glycolysis but is gradually being discovered to play the role of a universal metabolic fuel for energy via the 'lactate shuttle' moving between cells and transmitting signals. The glycolytic-dependent metabolism found in tumours and fast-growing cells has made lactate a pivotal player in energy metabolism reprogramming, which enables cells to obtain abundant energy in a short time. Moreover, lactate can provide favourable conditions for tumorigenesis by shaping the acidic tumour microenvironment, recruiting immune cells, etc. and the recently discovered lactate-induced lactylation moves even further on pro-tumorigenesis mechanisms of lactate production, circulation and utilization. As with other epigenetic modifications, lactylation can modify histone proteins to alter the spatial configuration of chromatin, affect DNA accessibility and regulate the expression of corresponding genes. What's more, the degree of lactylation is inseparable from the spatialized lactate concentration, which builds a bridge between epigenetics and metabolic reprogramming. Here, we review the important role of lactate in energy reprogramming, summarize the latest finding of lactylation in tumorigenesis and try to explore therapeutic strategies in oncotherapy that can kill two birds with one stone.

Divergent Synthesis of Pentacyclic Isoindolinones Enabled by Sequential Insertion of Two Different Isocyanides and Acid Promoted Cyclization of Ketenimines.

A palladium-catalyzed multicomponent reaction involving o-bromobenzaldehydes and two different isocyanides was developed to assemble series of isoindolinones with spiroindolenine or azepinoindole skeletons. This sequential insertion reaction features mild conditions, a wide substrate scope, and high efficiency. Preliminary mechanistic study indicated that the difference in steric hindrance between isocyanide components is crucial when regulating the reaction sequence, whereas the ligand also played an important role during the whole process.

Marine biological injuries and their medical management: A narrative review.

The marine environment can be extremely dangerous, and the harm caused by marine organisms when they contact the human body can be especially harmful, even deadly. Contact includes stings, bites, wounds, and consumption as food. In this article, the characteristics of the common marine biological injuries are summarized, the major marine organisms causing damage in China's marine waters are described, and injury prevention and treatment methods are discussed.

Genome-wide analysis of MYB family in Nicotiana benthamiana and the functional role of the key members in resistance to Bemisia tabaci.

MYB transcription factors (TFs) play a key role in plant resistance to abiotic and biotical stresses. However, little is currently known about their involvement in the plant defense to piercing-sucking insects. Here, we studied the MYB TFs that responded to and resisted Bemisia tabaci whitefly in the model plant Nicotiana benthamiana. Firstly, a total of 453 NbMYB TFs in N. benthamiana genome were identified and 182 R2R3-MYB TFs were analyzed for molecular characteristics, phylogenetic analysis, genetic structure, motif composition, and cis-elements. Then, six stress-related NbMYB genes were selected for further study. The expression pattern shows they were highly expressed in mature leaves and intensively induced upon whitefly attack. Combined with bioinformatic analysis, overexpression, ß-Glucuronidase (GUS) assay, and virus-induced silencing tests, we determined the transcriptional regulation of these NbMYBs on the genes in lignin biosynthesis and SA-signaling pathways. Meanwhile, we tested the performance of whitefly on plants with increased or silenced NbMYB genes expression and found that NbMYB42, NbMYB107, NbMYB163, and NbMYB423 were resistant to whitefly. Our results contribute to a comprehensive understanding of the MYB TFs in N. benthamiana. Furthermore, our findings will facilitate further studies on the role of MYB TFs in the interaction between plants and piercing-sucking insects.

Genome-Wide Identification of DUF668 Gene Family and Expression Analysis under Drought and Salt Stresses in Sweet Potato [Ipomoea batatas (L.) Lam].

The domain of unknown function 668 (DUF668) is a gene family that plays a vital role in responses to adversity coercion stresses in plant. However, the function of the DUF668 gene family is not fully understood in sweet potato. In this study, bioinformatics methods were used to analyze the number, physicochemical properties, evolution, structure, and promoter cis-acting elements of the IbDUF668 family genes, and RNA-seq and qRT-PCR were performed to detect gene expression and their regulation under hormonal and abiotic stress. A total of 14 IbDUF668 proteins were identified in sweet potato, distributed on nine chromosomes. By phylogenetic analysis, IbDUF668 proteins can be divided into two subfamilies. Transcriptome expression profiling revealed that many genes from DUF668 in sweet potato showed specificity and differential expression under cold, heat, drought, salt and hormones (ABA, GA3 and IAA). Four genes (IbDUF668-6, 7, 11 and 13) of sweet potato were significantly upregulated by qRT-PCR under ABA, drought and NaCl stress. Results suggest that the DUF668 gene family is involved in drought and salt tolerance in sweet potato, and it will further provide the basic information of DUF668 gene mechanisms in plants.

Hernandezine induces autophagic cell death in human pancreatic cancer cells via activation of the ROS/AMPK signaling pathway.

Hernandezine (Her) is a bisbenzylisoquinoline alkaloid extracted from the traditional Chinese herbal medicine Thalictrum glandulosissimum. Evidence shows that Her is a natural agonist of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and induces apoptosis and autophagy in tumor cells. In this study, we investigated the role of autophagy in Her-induced cell death in human pancreatic cancer cell lines. We showed that Her dose-dependently suppressed cell proliferation, promoted autophagy and induced autophagic death in pancreatic ductal adenocarcinoma (PDAC) cell lines Capan-1 and SW1990. The IC50 values of Her in inhibition of Capan-1 and SW1990 cells were 47.7 µM and 40.1 µM, respectively. Immunoblotting showed that Her (1-40 µM) promoted the conversion of LC3-I to LC3-II, and Her exerted concentration-dependent and time-dependent effects on autophagy activation in PDAC cells. In transmission electron microscopy and fluorescence image analysis, we found that autophagic vacuoles were significantly increased in Her-treated cells. Knockdown of ATG5, a key gene in the autophagy pathway, alleviated the activation of autophagy by Her. These results demonstrated that Her induced autophagy in PDAC cells. Intensely activated autophagy could promote cell death. The autophagy inhibitors, BafA1 and HCQ significantly inhibited Her-induced cell death, implying that Her induced autophagic cell death in PDAC cells. Moreover, we showed that Her activated autophagy by increasing the phosphorylation of AMPK and decreasing the phosphorylation of mTOR/p70S6K. Knockdown of AMPKα relieves the autophagic cell death induced by Her. Furthermore, Her concentration-dependently enhanced reactive oxygen species (ROS) generation in PDAC cells. Antioxidants could reduce the phosphorylation of AMPK and suppress autophagic cell death induced by Her. Our study provides evidence for the development of Her as a therapeutic agent for the treatment of pancreatic cancer.

Multimodality imaging differentiation of pancreatic neuroendocrine tumors and solid pseudopapillary tumors with a nomogram model: A large single-center study.

Background: Pancreatic neuroendocrine tumors (pNETs) and solid pseudopapillary tumors (SPTs) are two of the most common pancreatic neoplasms with different treatment procedures. However, the broad heterogeneity of pNETs and SPTs in clinical manifestations and radiological features often confuse the presurgical discrimination in clinical practice, and the clinical and molecular differentiation of the two tumors remains elusive to date. We presume that a large and comprehensive study into the multimodality features of pNETs and SPTs is necessary for precise clinical management. Methods: We collected and analyzed the clinicopathological information and multimodality features of nonfunctional pNET and SPT patients, for a total of 631 cases from 2006 to 2021. Univariate analysis of imaging features, including contrast-enhanced computed tomography (CT), magnetic resonance imaging, endoscopic ultrasound (EUS) and nuclear medicine imaging, and clinical characteristics was performed, and CT features and clinical information were integrated to establish a nomogram model. Results: We recruited 354 nonfunctional pNET and 277 SPT patients in our cohort. Regarding demographic information, pNET patients had a lower female percentage (55.4% vs. 72.9%), smaller tumor size (2.8 vs. 4.8 cm), and older age (53.4 vs. 35.3 years). In CT imaging and EUS, pNETs tended to appear as solid and homogenous lesions with strong enhancement intensity. Multifocal lesions, duct dilation, and lymph node (LN) enlargement were more likely to be observed in pNETs, while calcification was more common in SPT lesions. On positron emission tomography (PET)/CT, pNETs exhibited significant sensitivity to somatostatin receptor scintigraphy (SRS), with positive rates of 81.4% and 95% on 99mTc-HYNIC-TOC and 68Ga-DOTATATE PET/CT, respectively, while SPTs were all negative on SRS. Multivariate analysis identifies tumor size, age, enhancement intensity, calcification, and LN enlargement as statistically significant variables. Conclusions: Compared to SPT patients, pNET patients exhibit an older age and smaller tumor size. CT manifestations of strong intensity, LN enlargement, and no calcification could indicate a higher possibility of pNET. Meanwhile, the similarity in the immunohistochemical profile indicates that the two tumors could potentially develop from the same origin.

Palladium-Catalyzed Regioselective Diarylation/Deamination of Homoallylamines: Modular Assembly of 1,1,4,4-Tetraaryl-1,3-butadienes.

Herein, a novel palladium-catalyzed regioselective diarylation/deamination of homoallylamines is described. During the process, a ubiquitous free amine (NH2) was used as the directing group to accomplish the regioselective δ,δ-diarylation and it was removed in situ to form the privileged 1,1,4,4-tetraaryl-1,3-butadiene motif. This chelate-controlled Heck-type approach eliminates the traditional need of preinstalled and hard removable directing groups, proceeds under simple conditions, and exhibits good tolerance to a wide range of synthetically useful functional groups.