Delayed admission to hospital with proper prehospital treatments prevents severely burned patients from sepsis in China: A retrospective study.

BACKGROUND: Sepsis is one of the major causes of morbidity and mortality in burn patients. However, the optimal timing of admission which can minimize the probability of sepsis is still unclear. This study aims to determine the optimal time period of admission for severely burned patients and find out the possible reasons for it. METHOD: 185 victims to the Kunshan factory aluminum dust explosion accident, which happened on August 2nd, 2014, were studied. The optimal cutpoint for continuous variables in survival models was determined by means of the maximally selected rank statistic. Univariate and multivariate analyses were further conducted to verify that admission time was not a risk factor for sepsis. Subgroup analyses were performed to find out possible contributing factors for the result. RESULT: The cutoff point for admission time was determined as seven hours, which was supported by the survival curve (p < 0.001). Multivariate analysis showed that, in our study population, delayed admission time was not a risk factor for sepsis (HR = 0.610, 95 %CI = 0.415 - 0.896, p = 0.012). Subgroup analyses showed that "Tracheotomy before admission" (p = 0.002), "Whole blood transfusion" (p < 0.001), "Hemodynamic instability before admission" (p = 0.02), "Has a burn department in the hospital" (p = 0.009), "Has a burn ICU in the hospital" (p < 0.001), "Acute heart failure (AHF)" (p = 0.05), "acute respiratory distress syndrome (ARDS)" (p = 0.05) and "GI bleeding" (p = 0.04) were all statistically significant. CONCLUSION: In our study population, we found that delayed admission time was not a risk factor associated with a reduced incidence of sepsis among severely burned patients. This might be attributed to variations in prehospital treatments (whole blood transfusion and tracheotomy), whether the hospital had a burn department/ICU, and certain complications (AHF, ARDS and GI bleeding). It can be inferred that early prehospital care plays a crucial role in reducing sepsis risk among severe burn patients.

ING5 inhibits aerobic glycolysis of lung cancer cells by promoting TIE1-mediated phosphorylation of pyruvate dehydrogenase kinase 1 at Y163.

Aerobic glycolysis is critical for tumor growth and metastasis. Previously, we have found that the overexpression of the inhibitor of growth 5 (ING5) inhibits lung cancer aggressiveness and epithelial-mesenchymal transition (EMT). However, whether ING5 regulates lung cancer metabolism reprogramming remains unknown. Here, by quantitative proteomics, we showed that ING5 differentially regulates protein phosphorylation and identified a new site (Y163) of the key glycolytic enzyme PDK1 whose phosphorylation was upregulated 13.847-fold. By clinical study, decreased p-PDK1Y163 was observed in lung cancer tissues and correlated with poor survival. p-PDK1Y163 represents the negative regulatory mechanism of PDK1 by causing PDHA1 dephosphorylation and activation, leading to switching from glycolysis to oxidative phosphorylation, with increasing oxygen consumption and decreasing lactate production. These effects could be impaired by PDK1Y163F mutation, which also impaired the inhibitory effects of ING5 on cancer cell EMT and invasiveness. Mouse xenograft models confirmed the indispensable role of p-PDK1Y163 in ING5-inhibited tumor growth and metastasis. By siRNA screening, ING5-upregulated TIE1 was identified as the upstream tyrosine protein kinase targeting PDK1Y163. TIE1 knockdown induced the dephosphorylation of PDK1Y163 and increased the migration and invasion of lung cancer cells. Collectively, ING5 overexpression-upregulated TIE1 phosphorylates PDK1Y163, which is critical for the inhibition of aerobic glycolysis and invasiveness of lung cancer cells.

Molecular investigation of Blastocystis in children and calves in Bangladesh.

BACKGROUND: Blastocystis, a widely distributed zoonotic protozoan infecting both humans and numerous animals, remains poorly understood with its potential medical and veterinary significance. This study examined the molecular occurrence and genetic variation of Blastocystis in children and calves in Bangladesh to explore cross-species transmission and disease burden. METHODS: In total, 998 DNA samples were investigated, comprising 299 stool DNA from children and 699 fecal DNA from calves, using polymerase chain reaction and sequencing of the small subunit ribosomal RNA (SSU rRNA) gene. RESULTS: This study detected Blastocystis in 5.35% of the children and 14.74% of the calves. While slight variations in occurrence rates were observed across different study variables, none were statistically significant. The occurrence was highest among children under 5 years and calves aged 1-3 months. Regarding breed, the Holstein Friesian cross and the Jersey cross exhibited higher rates of infection. Conversely, occurrences were lower among children and calves in Gazipur district. The remaining parameters displayed nearly equivalent percentages of Blastocystis. The subtypes identified in children included ST1, ST3, and ST4, with ST1 comprising 50% of them. ST3 and ST4 were also found in calves, alongside ST10 (55.34%) being the most prevalent. Other subtypes found in calves were ST14, ST21, and ST24-ST26. CONCLUSIONS: This study found that Blastocystis is more common in calves than in children in Bangladesh, with genetic diversity of nine subtypes. The common occurrence of identical variants of two subtypes in both populations suggests potential zoonotic transmission, highlighting the necessity for further molecular investigations and comprehensive measures within the One Health framework to mitigate public health risks.

Advances and clinical challenges of mesenchymal stem cell therapy.

In recent years, cell therapy has provided desirable properties for promising new drugs. Mesenchymal stem cells are promising candidates for developing genetic engineering and drug delivery strategies due to their inherent properties, including immune regulation, homing ability and tumor tropism. The therapeutic potential of mesenchymal stem cells is being investigated for cancer therapy, inflammatory and fibrotic diseases, among others. Mesenchymal stem cells are attractive cellular carriers for synthetic nanoparticles for drug delivery due to their inherent homing ability. In this review, we comprehensively discuss the various genetic and non-genetic strategies of mesenchymal stem cells and their derivatives in drug delivery, tumor therapy, immune regulation, tissue regeneration and other fields. In addition, we discuss the current limitations of stem cell therapy and the challenges in clinical translation, aiming to identify important development areas and potential future directions.

A 10-year mono-center study on patients with burns ≥70% TBSA: prediction model construction and multi-center validation: retrospective cohort.

BACKGROUND: Burn injuries with ≥70% total body surface area (TBSA) are especially acute and life-threatening, leading to severe complications and terrible prognosis, while a powerful model for prediction of overall survival (OS) is lacked. The objective of this study is to identify prognostic factors for the OS of patients with burn injury ≥70% TBSA, construct and validate a feasible predictive model. MATERIALS AND METHODS: Patients diagnosed with burns ≥70% TBSA admitted and treated between 2010 and 2020 in our hospital were included. A cohort of the patients from the Kunshan explosion were assigned as the validation set. The Chi-square test and K-M survival analysis were conducted to identify potential predictors for OS. Then, multi-variate Cox regression analysis was performed to identify the independent factors. Afterwards, we constructed a nomogram to predict OS probability. Finally, the Kunshan cohort was applied as an external validation set. RESULTS: Gender, the percentage of third- and fourth-degree burn as well as organ dysfunction were identified as significant independent factors. A nomogram only based on the factors of the individuals was built and evidenced to have promising predictive accuracy, accordance, and discrimination by both internal and external validation. CONCLUSIONS: This study recognized significant influencing factors for the OS of patients with burns ≥70% TBSA. Furthermore, our nomogram proved to be an effective tool for doctors to quickly evaluate patients' outcomes and make appropriate clinical decisions at an early stage of treatment.

Molecular characterization and zoonotic risk assessment of Cryptosporidium spp. in children and calves in Bangladesh.

Cryptosporidium is a gastro-intestinal protozoan parasite that has been found to infect both humans and livestock. This study investigated the parasite in 998 fecal samples from Bangladeshi children (n = 299) and calves (n = 699) to determine its prevalence, genetic variation, and zoonotic importance. The nested PCR and sequencing of the SSU rRNA gene in the samples showed a Cryptosporidium infection rate of 2.3% (7/299) in children and 15.7% (110/699) in calves. Statistical analysis revealed insignificant variations in Cryptosporidium infections among children across age, gender, and study area, while in calves, the infection rate significantly differed based on location and breed. Genotyping of seven human isolates of Cryptosporidium confirmed C. hominis (n = 5) and C. parvum (n = 2). After characterizing 110 Cryptosporidium isolates from calves, C. andersoni (n = 55), C. ryanae (n = 29), C. bovis (n = 14), C. parvum (n = 10), C. ubiquitum (n = 1), and C. occultus (n = 1) were identified. Cryptosporidium hominis and C. parvum-positive samples were further subjected to nested PCR and sequencing of the glycoprotein 60 (gp60) gene for subtyping. Four C. hominis subtypes (IaA19R3, IaA23R3, IbA9G3, and IdA15G1) and one C. parvum subtype (IIdA15G1) were observed. In conclusion, Cryptosporidium was prevalent in calves but less common in children in the study locations, and the presence of zoonotic Cryptosporidium species and subtypes in calves raises concerns regarding zoonotic transmission to humans.

Chromosome genome assembly of the Camphora longepaniculata (Gamble) with PacBio and Hi-C sequencing data.

Introduction: Camphora longepaniculata, a crucial commercial crop and a fundamental component of traditional Chinese medicine, is renowned for its abundant production of volatile terpenoids. However, the lack of available genomic information has hindered pertinent research efforts in the past. Methods: To bridge this gap, the present study aimed to use PacBio HiFi, short-read, and highthroughput chromosome conformation capture sequencing to construct a chromosome-level assembly of the C. longepaniculata genome. Results and discussion: With twelve chromosomes accounting for 99.82% (766.69 Mb) of the final genome assembly, which covered 768.10 Mb, it was very complete. Remarkably, the assembly's contig and scaffold N50 values are exceptional as well-41.12 and 63.78 Mb, respectively-highlighting its excellent quality and intact structure. Furthermore, a total of 39,173 protein-coding genes were predicted, with 38,766 (98.96%) of them being functionally annotated. The completeness of the genome was confirmed by the Benchmarking Universal Single-Copy Ortholog evaluation, which revealed 99.01% of highly conserved plant genes. As the first comprehensive assembly of the C. longepaniculata genome, it provides a crucial starting point for deciphering the complex pathways involved in terpenoid production. Furthermore, this excellent genome serves as a vital resource for upcoming research on the breeding and genetics of C. longepaniculata.

miR-181d targets BCL2 to regulate HCT-8 cell apoptosis and parasite burden in response to Cryptosporidium parvum infection via the intrinsic apoptosis pathway.

Cryptosporidium parvum is an important zoonotic pathogen that is studied worldwide. MicroRNAs (miRNAs) act as post-transcriptional regulators and may play a key role in modulating host epithelial responses following Cryptosporidium infection. Our previous study has shown that C. parvum downregulates the expression of miR-181d through the p50-dependent TLRs/NF-κB pathway. However, the mechanism by which miR-181d regulates host cells in response to C. parvum infection remains unclear. The present study found that miR-181d downregulation inhibited cell apoptosis and increased parasite burden in HCT-8 cells after C. parvum infection. Bioinformatics analysis and luciferase reporter assays have shown that BCL2 was a target gene for miR-181d. Moreover, BCL2 overexpression and miR-181d downregulation had similar results. To further investigate the mechanism by which miR-181d regulated HCT-8 cell apoptosis during C. parvum infection, the expression of molecules involved in the intrinsic apoptosis pathway was detected. Bax, caspase-9, and caspase-3 expression was decreased at 4, 8, 12, and 24 hpi and upregulated at 36 and 48 hpi. Interfering with the expression of miR-181d or BCL2 significantly affected the expression of molecules in the intrinsic apoptosis pathway. These data indicated that miR-181d targeted BCL2 to regulate HCT-8 cell apoptosis and parasite burden in response to C. parvum infection via the intrinsic apoptosis pathway. These results allowed us to further understand the regulatory mechanisms of host miRNAs during Cryptosporidium infection, and provided a theoretical foundation for the design and development of anti-cryptosporidiosis drugs.

Design of an ultrafast plasmonic nanolaser for high-intensity broadband emission operating at room temperature.

We propose a plasmonic nanolaser based on a metal-insulator-semiconductor-insulator-metal (MISIM) structure, which effectively confines light on a subwavelength scale (∼λ/14). As the pump power increases, the proposed plasmonic nanolaser exhibits broadband output characteristics of 20 nm, and the maximum output power can reach 20 µW. Furthermore, the carrier lifetime at the upper energy level in our proposed structure is measured to be about 400 fs using a double pump-probe excitation. The ultrafast characteristic is attributed to the inherent Purcell effect of plasmonic systems. Our work paves the way toward deep-subwavelength mode confinement and ultrafast femtosecond plasmonic lasers in spaser-based interconnected, eigenmode engineering of plasmonic nanolasers, nano-LEDs, and spontaneous emission control.

Portulaca oleracea exhibited anti-coccidian activity, fortified the gut microbiota of Hu lambs.

Coccidia of the genus Eimeria are important pathogens that cause coccidiosis in livestock and poultry. Due to the expansion of intensive farming, coccidiosis has become more difficult to control. In addition, the continued use of anti-coccidiosis drugs has led to drug resistance and residue. Some herbs used in traditional Chinese medicine (TCM) have been shown to alleviate the clinical symptoms of coccidiosis, while enhancing immunity and growth performance (GP) of livestock and poultry. Previous in vitro and in vivo studies have reported that the TCM herb Portulaca oleracea exhibited anti-parasitic activities. In total, 36 female Hu lambs were equally divided into six treatment groups: PL (low-dose P. oleracea), PH (high-dose P. oleracea), PW (P. oleracea water extract), PE (P. oleracea ethanol extract), DIC (diclazuril), and CON (control). The treatment period was 14 days. The McMaster counting method was used to evaluate the anti-coccidiosis effects of the different treatments. Untargeted metabolomics and 16S rRNA gene sequencing were used to investigate the effects of treatment on the gut microbiota (GM) and GP. The results showed that P. oleracea ameliorated coccidiosis, improved GP, increased the abundances of beneficial bacteria, and maintained the composition of the GM, but failed to completely clear coccidian oocysts. The Firmicutes to Bacteroides ratio was significantly increased in the PH group. P. oleracea increased metabolism of tryptophan as well as some vitamins and cofactors in the GM and decreased the relative content of arginine, tryptophan, niacin, and other nutrients, thereby promoting intestinal health and enhancing GP. As an alternative to the anti-coccidiosis drug DIC, P. oleracea effectively inhibited growth of coccidia, maintained the composition of the GM, promoted intestinal health, and increased nutrient digestibility.

Systematic Analysis of the Relationship Between Elevated Zinc and Epilepsy.

Previous studies have indicated a potential relationship between zinc and epilepsy. The aim of this study is to investigate the causal relationship between zinc, zinc-dependent carbonic anhydrase, and gray matter volume in brain regions enriched with zinc and epilepsy, as well as explore the possible mechanisms by which zinc contributes to epilepsy. First, this study assessed the risk causality between zinc, carbonic anhydrase, and gray matter volume alterations in zinc-enriched brain regions and various subtypes of epilepsy based on Two-sample Mendelian randomization analysis. And then, this study conducted GO/KEGG analysis based on colocalization analysis, MAGMA analysis, lasso regression, random forest model, and XGBoost model. The results of Mendelian randomization analyses showed a causal relationship between zinc, carbonic anhydrase-4, and generalized epilepsy (p = 0.044 , p = 0.010). Additionally, carbonic anhydrase-1 and gray matter volume of the caudate nucleus were found to be associated with epilepsy and focal epilepsy (p = 0.014, p = 0.003 and p = 0.022, p = 0.009). A colocalization relationship was found between epilepsy and focal epilepsy (PP.H4.abf = 97.7e - 2). Meanwhile, the MAGMA analysis indicated that SNPs associated with epilepsy and focal epilepsy were functionally localized to zinc-finger-protein-related genes (p < 1.0e - 5). The genes associated with focal epilepsy were found to have a molecular function of zinc ion binding (FDR = 2.3e - 6). After the onset of epilepsy, the function of the gene whose expression changed in the rats with focal epilepsy was enriched in the biological process of vascular response (FDR = 4.0e - 5). These results revealed mechanism of the increased risk of epilepsy caused by elevated zinc may be related to the increase of zinc ion-dependent carbonic anhydrase or the increase of the volume of zinc-rich caudate gray matter.

The Mechanism of Manipulating Chirality and Chiral Sensing Based on Chiral Plexcitons in a Strong-Coupling Regime.

Manipulating plasmonic chirality has shown promising applications in nanophotonics, stereochemistry, chirality sensing, and biomedicine. However, to reconfigure plasmonic chirality, the strategy of constructing chiral plasmonic systems with a tunable morphology is cumbersome and complicated to apply for integrated devices. Here, we present a simple and effective method that can also manipulate chirality and control chiral light-matter interactions only via strong coupling between chiral plasmonic nanoparticles and excitons. This paper presents a chiral plexcitonic system consisting of L-shaped nanorod dimers and achiral molecule excitons. The circular dichroism (CD) spectra in our strong-coupling system can be calculated by finite element method simulations. We found that the formation of the chiral plexcitons can significantly modulate the CD spectra, including the appearance of new hybridized peaks, double Rabi splitting, and bisignate anti-crossing behaviors. This phenomenon can be explained by our extended coupled-mode theory. Moreover, we explored the applications of this method in enantiomer ratio sensing by using the properties of the CD spectra. We found a strong linear dependence of the CD spectra on the enantiomer ratio. Our work provides a facile and efficient method to modulate the chirality of nanosystems, deepens our understanding of chiral plexcitons in nanosystems, and facilitates the development of chiral devices and chiral sensing.

Realization of exciton-polariton optical chirality based on strong coupling between intrinsic chiral quasibound states in the continuum and monolayer WS2.

Hybrid quasiparticles produced by the strong interaction between nanostructures and excitons will exhibit optical chirality when one of the coupled components is chiral. Due to the tunability of hybrid states, the coupled system has potential applications in chiral devices and chiral sensing. However, reported chiral materials including chiral molecules and three-dimensional chiral structures in the coupled system limit the application due to the weak chiroptical responses and difficult fabrication, respectively. In this paper, we design chiral quasibound states in the continuum (q-BIC) metasurface by introducing planar symmetry-breaking and z-axis perturbation into an array structure whose unit cell is a C4 rotational symmetric disk. By tuning the polarization state of the eigenmode, a significant chiroptical response is obtained in our q-BIC metasurface. Furthermore, mode splitting is observed not only in the reflection spectrum but also in the circular dichroism (CD) spectrum in the chiral q-BIC and monolayer WS2 strong coupling system, which indicates the realization of the exciton-polariton optical chirality. More importantly, one order of magnitude difference in the reflection to left and right circularly polarized light is achieved resulting in significant CD signals. Our work provides a new strategy to realize the exciton polaritons with significant chiroptical responses, which exhibits promising applications in on-chip chiral devices.

Molecular characterization of Cryptosporidium spp. and Giardia duodenalis in pet cats in Henan Province, central China.

Cryptosporidium spp. and G. duodenalis often infect humans, cats, and other mammals, causing diarrhea and being responsible for numerous outbreaks of waterborne and foodborne infections worldwide. The rapid increase in the number of pet cats poses a substantial public health risk. However, there were few reports about the infection of Cryptosporidium spp. and G. duodenalis infections in pet cats in Henan Province, central China. Thus, to understand the prevalence and genetic distribution of Cryptosporidium spp. and G. duodenalis in pet cats, and to evaluate the zoonotic potential, possible transmission routes and public health implications of isolates, fecal samples (n = 898) were randomly collected from pet cats in 11 cities in Henan Province, central China. Nested PCR based on the SSU rRNA gene and bg gene was used to the prevalence of Cryptosporidium spp. and G. duodenalis, respectively. The prevalence was 0.8 % (7/898) and 2.0 % (18/898) for Cryptosporidium spp. and G. duodenalis respectively. Additionally, the Cryptosporidium spp. positive isolates were identified as C. parvum subtype IIdA19G1 by gp60 gene. In the present study, the IIdA19G1 subtype was discovered in pet cats for the first time in China, enriching the information on the host type and geographical distribution of Cryptosporidium spp. in China. For G. duodenalis, a total of 18 G. duodenalis positive samples were identified, belonging to four assemblages: a zoonotic assemblage A1 (4/898), three host-specific assemblages C (8/898), D (5/898), and F (1/898). Interestingly, we found that pet cats infected with Cryptosporidium spp. and G. duodenalis are more likely to experience emaciation symptoms compared to the negative group. More importantly, the prevalence of Cryptosporidium spp. and G. duodenalis detected in the present study were low, but the subtype IIdA19G1 of Cryptosporidium spp. and the assemblages A1, C, D, and F of G. duodenalis have the potential for zoonotic transmission. Thus, we should focus on preventing and controlling the risk of cross-species transmission that may occur in pet cats in Henan Province.

The global prevalence of Cyclospora cayetanensis infection: A systematic review, meta-analysis, and meta-regression.

Cyclospora cayetanensis (C. cayetanensis) is a significant pathogen that causes diarrheal illness and causes large foodborne diarrhea outbreaks in the USA and Canada. However, there is currently a lack of published meta-analysis on the prevalence of C. cayetanensis infection in the global population. A real estimation of a disease prevalence should always be done on the basis of studies designed for that purpose. We conducted a comprehensive search of various databases for articles pertaining to the prevalence of C. cayetanensis infection in humans, spanning from the inception of these databases to March 10, 2023. Utilizing a random effects model, we estimated the prevalence of C. cayetanensis infection in humans. Our analysis included a total of 150 datasets sourced from 42 different countries, which were ultimately selected for the final quantitative assessment. The prevalence of C. cayetanensis infection in humans worldwide was estimated to be 3.4 % (5636/166,611). Notably, Africa exhibited the highest prevalence rate at 5.9 % (606/11,068). Further subgroup analysis revealed a significantly higher infection rate in humans residing in low-income countries (7.6 %, 83/921) compared to those in lower-middle-income countries (4.8 %, 3280/48,852), upper-middle-income countries (2.9 %, 2194/99,419), and high-income countries (0.4 %, 79/17,419). The results indicate that the global prevalence of C. cayetanensis infection in humans is relatively low, despite its extensive geographical distribution and children were found to be more susceptible to C. cayetanensis infection compared to those adults. Sensitivity analysis revealed that one study significantly affects the prevalence of C. cayetanensis, which was adjusted to 2.9 % (4017/160,049; 95 % CI: 2.7-3.1 %) by excluding this study. The findings highlight the relatively high prevalence of C. cayetanensis infection in low-income countries and among humans with diarrhea, particularly in Africa. Consequently, routine surveillance for intestinal protozoa is crucial in these regions.

Characteristics of the Blockage from Air Nozzle Guide Duct in Circulating the Fluidized-Bed Coal Gasifier and Its Formation Mechanism.

Blockage is often generated in the air nozzle guide duct in a circulating fluidized-bed coal gasifier (CFBG), especially with Zhundong sub-bituminous coal (ZSBC) as the raw material. A typical example is found in one CFBG sample from Xinjiang Yihua Chemical Industry Co, Ltd. The serious blockage can be observed obviously. As so far, it is not clear for the characteristics and generation mechanism of the blockage. For analysis, the blockage can be classified into two parts, wall-layer blockage (WLB) and center-layer blockage (CLB). To inhibit its formation, it is of significance to analyze the composition, surface morphology, and formation mechanism of the two blockages. In our experiments, WLB and CLB were tested by XRF, XRD, FTIR, SEM-EDS, and SEM-mapping methods. Results showed that WLB presents high content of Fe, Cr, and Ni, and Fe mainly existed in the form of metal oxides. CLB is dominated by Si (43.04%), derived from silica and alkali and alkaline-earth metals silicates, and the migration of Fe, Cr, and Ni elements from the duct material was observed. Compared with WLB, from FTIR analysis, CLB contains more inorganic minerals, and the absorption peak of inorganic minerals is mainly attributed to asymmetric Si-O-Si. Many fine particles are attached to the surface of the WLB, while the surface of the CLB is smooth, and there is noticeable raised texture, which is presumed to be the result of particle melting and agglomerating as the bottom ash enters the duct in the gasification process. For the formation of the blockage, this paper speculates that it is mainly due to the difference in flow resistance near the air nozzle outlet, resulting in the formation of a flow dead zone at the bottom of the gasifier, which leads to large amounts of ash overcoming the outlet resistance and leaking into the air nozzle, and next, the ash corrodes in the tube, resulting in wall deposition and ultimately blocking the air guide duct. Two methods can be tried to avoid or inhibit the formation of blockage in the duct, including optimizing air nozzle with more wear-resistant and heat-resistant materials and adjusting the distance between air nozzles to avoid mutual interference from ash particles.

METTL3-mediated RanGAP1 promotes colorectal cancer progression through the MAPK pathway by recruiting YTHDF1.

Ran GTPase activating protein 1 (RanGAP1) has been implicated in various diseases, but its role in colorectal cancer (CRC) progression remains unclear. Using tumor tissues and public databases, we found that RanGAP1 was significantly upregulated in CRC tissues and was associated with poor prognosis of patients. N6-methyladenosine (m6A) was found to play an important role in higher expression of RanGAP1. MeRIP-seq, RIP-qPCR, Luciferase reporter assays and other related experiment elucidated the molecular mechanism underlying m6A modification of RanGAP1. Besides, cell function experiments and xenograft tumor models corroborated the function of RanGAP1 in CRC progression. By RNA-seq and related analysis, RanGAP1 was verified to influent CRC progression via the Mitogen-Activated Protein Kinase (MAPK) signaling pathway. Therefore, N6-methyladenosine modification of RanGAP1 by METTL3/YTHDF1 plays a role in CRC progression through the MAPK pathway and could be a potential biomarker and therapeutic target for CRC. Schematic diagram showed that N6-methyladenosine modification of RanGAP1 promotes CRC progression via the MAPK signaling pathway.

Electrochemical decarboxylative alkylation of ß-ketoacids with phenol derivatives.

An electrochemical method for the decarboxylative alkylation of ß-ketoacids with phenol derivatives has been developed. The protocol was carried out in readily available unseparated cells at room temperature in the absence of catalysts and oxidants. The corresponding aryl ketones were obtained in satisfactory yields without additional electrolytes, and were easy to produce in gram-scale synthesis. Based on control experiments and cyclic voltammetry, a plausible reaction mechanism was proposed.

Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies.

We performed comprehensive proteogenomic characterization of small cell lung cancer (SCLC) using paired tumors and adjacent lung tissues from 112 treatment-naive patients who underwent surgical resection. Integrated multi-omics analysis illustrated cancer biology downstream of genetic aberrations and highlighted oncogenic roles of FAT1 mutation, RB1 deletion, and chromosome 5q loss. Two prognostic biomarkers, HMGB3 and CASP10, were identified. Overexpression of HMGB3 promoted SCLC cell migration via transcriptional regulation of cell junction-related genes. Immune landscape characterization revealed an association between ZFHX3 mutation and high immune infiltration and underscored a potential immunosuppressive role of elevated DNA damage response activity via inhibition of the cGAS-STING pathway. Multi-omics clustering identified four subtypes with subtype-specific therapeutic vulnerabilities. Cell line and patient-derived xenograft-based drug tests validated the specific therapeutic responses predicted by multi-omics subtyping. This study provides a valuable resource as well as insights to better understand SCLC biology and improve clinical practice.

Assessment of potential zoonotic transmission of Giardia duodenalis from dogs and cats.

Giardia duodenalis is one of the major causes of diarrhea among humans, especially in young children. Statistical analysis revealed that the pooled prevalence of G. duodenalis in humans, dogs, and cats was 9.72% (10,921/112383), 15.60% (7510/48140), and 14.53% (1125/7740), respectively. Unquestionably, the canine-specific assemblages C and D and the feline-specific assemblage F were the dominant genotypes in dogs and cats, respectively. Additionally, the prevalence of zoonotic G. duodenalis assemblages (A and B) in dogs and cats was 23.07% (875/3792) and 41.42% (169/408), respectively, implying that the potential transmission of G. duodenalis from dogs and cats to human infection cannot be ignored. The highest frequency of potentially zoonotic assemblages was found among working dogs (3.55%, 25/705) and the 1-5 age group (22.92%, 11/48). In summary, dogs and cats have a significant role in the zoonotic transmission of G. duodenalis due to their close contact with humans and the higher frequency presence of zoonotic assemblages. Further studies are necessary to explore the presence of G. duodenalis among humans and animals and in environmental samples. Researchers should adopt a one-health approach to gain a deeper understanding of G. duodenalis in dogs and cats and potential transmission routes to humans.