Diarylheptanoid 35d overcomes EGFR TKI resistance by inducing hsp70-mediated lysosomal degradation of EGFR in EGFR-mutant lung adenocarcinoma.

Epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma (LUAD) patients often respond to EGFR tyrosine kinase inhibitors (TKIs) initially but eventually develop resistance to TKIs. The switch of EGFR downstream signaling from TKI-sensitive to TKI-insensitive is a critical mechanism-driving resistance to TKIs. Identification of potential therapies to target EGFR effectively is a potential strategy to treat TKI-resistant LUADs. In this study, we developed a small molecule diarylheptanoid 35d, a curcumin derivative, that effectively suppressed EGFR protein expression, killed multiple TKI-resistant LUAD cells in vitro, and suppressed tumor growth of EGFR-mutant LUAD xenografts with variant TKI-resistant mechanisms including EGFR C797S mutations in vivo. Mechanically, 35d triggers heat shock protein 70-mediated lysosomal pathway through transcriptional activation of several components in the pathway, such as HSPA1B, to induce EGFR protein degradation. Interestingly, higher HSPA1B expression in LUAD tumors associated with longer survival of EGFR-mutant, TKI-treated patients, suggesting the role of HSPA1B on retarding TKI resistance and providing a rationale for combining 35d with EGFR TKIs. Our data showed that combination of 35d significantly inhibits tumor reprogression on osimertinib and prolongs mice survival. Overall, our results suggest 35d as a promising lead compound to suppress EGFR expression and provide important insights into the development of combination therapies for TKI-resistant LUADs, which could have translational potential for the treatment of this deadly disease.

Systematic calibration of epitranscriptomic maps using a synthetic modification-free RNA library.

Recent years have witnessed rapid progress in the field of epitranscriptomics. Functional interpretation of the epitranscriptome relies on sequencing technologies that determine the location and stoichiometry of various RNA modifications. However, contradictory results have been reported among studies, bringing the biological impacts of certain RNA modifications into doubt. Here, we develop a synthetic RNA library resembling the endogenous transcriptome but without any RNA modification. By incorporating this modification-free RNA library into established mapping techniques as a negative control, we reveal abundant false positives resulting from sequence bias or RNA structure. After calibration, precise and quantitative mapping expands the understanding of two representative modification types, N6-methyladenosine (m6A) and 5-methylcytosine (m5C). We propose that this approach provides a systematic solution for the calibration of various RNA-modification mappings and holds great promise in epitranscriptomic studies.

Association between Whole Grain Intake and Chronic Kidney Disease.

BACKGROUND: The relationship between whole grain intake and chronic kidney disease (CKD) remains uncertain. OBJECTIVE: This study aimed to evaluate the association between whole grain intake and risk of CKD in Chinese adults. METHODS: The present cross-sectional study used data from the China Health and Nutrition Survey conducted in 2009. Whole grain intake was measured using 3 consecutive 24-h dietary recalls and a household food inventory. A multivariable logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of CKD. In addition, a restricted cubic spline was used to investigate the dose‒response relationship between whole grain and risk of CKD. RESULTS: A total of 6747 participants were included, 728 of whom had CKD. Compared with those in the lowest whole grain intake group, those in the higher grain intake group had an inverse association with risk of CKD (Q2: adjusted OR 0.70, 95% CI: 0.54, 0.89; Q3: adjusted OR 0.54, 95% CI: 0.42, 0.69; and Q4: adjusted OR 0.29, 95% CI: 0.21, 0.41). The association between whole grain intake and CKD seems to be stronger for individuals who were male (P for interaction = 0.008) or smokers (P for interaction = 0.013). In addition, the restricted cubic spline suggested an obvious L-shaped correlation. CONCLUSIONS: Increased whole grain intake was associated with a decreased risk of CKD in Chinese adults.

Associations between whole grains intake and new-onset hypertension: a prospective cohort study.

IMPORTANCE: Epidemiological evidences regarding the association between whole grain intake and the risk of new-onset hypertension are still controversial. OBJECTIVE: We aimed to investigate the relationship between whole grain intake and new-onset hypertension and examine possible effect modifiers in the general population. METHODS: A total of 10,973 participants without hypertension from the China Health and Nutrition Survey were enrolled, with follow-up beginning in 1997 and ending in 2015. Whole grain intake was assessed by 3 consecutive 24-h dietary recalls combined with a household food inventory. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression model after adjusting for potential risk factors. RESULTS: During a median follow-up of 7.0 years, 3,733 participants developed new-onset hypertension. The adjusted HRs (95% CIs) were as follows: for quartile 2 (HR: 0.52; 95% CI: 0.47-0.57), quartile 3 (HR: 0.46; 95% CI: 0.42-0.51), and quartile 4 (HR: 0.35; 95% CI: 0.31-0.38), compared with quartile 1. Different types of whole grain types, including wheat (adjusted HR, 0.35; 95% CI, 0.32-0.39), maize (adjusted HR, 0.50; 95% CI, 0.42-0.59), and millet (adjusted HR, 0.38; 95% CI, 0.30-0.48), showed significant associations with a reduced risk of hypertension. The association between whole grain intake and new-onset hypertension was stronger in individuals with older age (P for interaction < 0.001) and higher BMI (P for interaction < 0.001). CONCLUSION: Higher consumption of whole grains was significantly associated with a lower risk of new-onset hypertension. This study provides further evidence supporting the importance of increasing whole grain intake for hypertension prevention among Chinese adults.

Cytotoxic and Antibacterial Meroterpenoids Isolated from the Marine-Derived Fungus Talaromyces sp. M27416.

Three novel meroterpenoids, taladrimanins B-D (1-3), were isolated from the marine-derived fungus Talaromyces sp. M27416, alongside three biogenetically related compounds (4-6). We delineated taladrimanin B's (1) structure using HRESIMS and NMR, confirmed its configuration via quantum chemical NMR analysis and DP4+ methodology, and verified it through X-ray crystallography. ECD calculations determined the absolute configuration of compound 1, while comparative NMR and ECD analyses elucidated the absolute configurations of 2 and 3. These compounds are drimane-type meroterpenoids with a C10 polyketide unit (8R-configuration). We proposed a biosynthetic pathway and noted that compound 1 showed cytotoxic activity against MKN-45 and 5637 cell lines and selective antibacterial effects against Staphylococcus aureus CICC 10384.

Cytotoxic Pentaketide-Sesquiterpenes from the Marine-Derived Fungus Talaromyces variabilis M22734.

Talaromyces, a filamentous fungus widely distributed across terrestrial and marine environments, can produce a diverse array of natural products, including alkaloids, polyketones, and polyketide-terpenoids. Among these, chrodrimanins represented a typical class of natural products. In this study, we isolated three previously undescribed pentaketide-sesquiterpenes, 8,9-epi-chrodrimanins (1-3), along with eight known compounds (4-11). The structures of compounds 1-3 were elucidated using nuclear magnetic resonance (NMR) and mass spectrometry (MS), while their absolute configurations were determined through X-ray crystallography and electronic circular dichroism (ECD) computations. The biosynthetic pathways of compounds 1-3 initiate with 6-hydroxymellein and involve multiple stages of isoprenylation, cyclization, oxidation, and acetylation. We selected four strains of gastrointestinal cancer cells for activity evaluation. We found that compound 3 selectively inhibited MKN-45, whereas compounds 1 and 2 exhibited no significant inhibitory activity against the four cell lines. These findings suggested that 8,9-epi-chrodrimanins could serve as scaffold compounds for further structural modifications, potentially leading to the development of targeted therapies for gastric cancer.

Human molybdenum exposure risk in industrial regions of China: New critical effect indicators and reference dose.

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 µg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 µg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.

Autophagy-Mediated Phosphate Homeostasis in Arabidopsis Involves Modulation of Phosphate Transporters.

Autophagy in plants is regulated by diverse signaling cascades in response to environmental changes. Fine-tuning of its activity is critical for the maintenance of cellular homeostasis under basal and stressed conditions. In this study, we compared the Arabidopsis autophagy-related (ATG) system transcriptionally under inorganic phosphate (Pi) deficiency versus nitrogen deficiency and showed that most ATG genes are only moderately upregulated by Pi starvation, with relatively stronger induction of AtATG8f and AtATG8h among the AtATG8 family. We found that Pi shortage increased the formation of GFP-ATG8f-labeled autophagic structures and the autophagic flux in the differential zone of the Arabidopsis root. However, the proteolytic cleavage of GFP-ATG8f and the vacuolar degradation of endogenous ATG8 proteins indicated that Pi limitation does not drastically alter the autophagic flux in the whole roots, implying a cell type-dependent regulation of autophagic activities. At the organismal level, the Arabidopsis atg mutants exhibited decreased shoot Pi concentrations and smaller meristem sizes under Pi sufficiency. Under Pi limitation, these mutants showed enhanced Pi uptake and impaired root cell division and expansion. Despite a reduced steady-state level of several PHOSPHATE TRANSPORTER 1s (PHT1s) in the atg root, cycloheximide treatment analysis suggested that the protein stability of PHT1;1/2/3 is comparable in the Pi-replete wild type and atg5-1. By contrast, the degradation of PHT1;1/2/3 is enhanced in the Pi-deplete atg5-1. Our findings reveal that both basal autophagy and Pi starvation-induced autophagy are required for the maintenance of Pi homeostasis and may modulate the expression of PHT1s through different mechanisms.

Inhibition of HIST1H2AB suppresses the proliferation of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is one of the common causes of cancer-related deaths worldwide. Histone cluster 1 H2A family member b (HIST1H2AB) is a member of the histone H2A family. Bioinformatic analyses have revealed that HIST1H2AB is highly expressed in some cancers and might be an oncogene. However, information on the function of HIST1H2AB in lung adenocarcinoma is limited. METHODS: The expression of HIST1H2AB was analyzed in normal lung, lung adenocarcinoma and paracancerous tissues from The Cancer Genome Atlas (TCGA) database and immunohistochemistry staining. It was further verified in the relative cell lines using real-time quantitative polymerase chain reaction (RT-qPCR). When the adenocarcinoma cells lines (A549 and H1299) were successfully transfected with shHIST1H2AB or an empty plasmid packaged into a lentivirus, cell proliferation was detected using Celigo fluorescence cell-counting, colony formation and annexin V-allophycocyanin assays. Twenty nude mice were subcutaneously injected with A549 cells transfected with shHIST1H2AB or empty plasmid; the tumor size was recorded on day 25 and then measured every 3 days thereafter. The final tumor weight was measured on day 37. Significantly differentially expressed genes were analyzed using a human gene expression array. Furthermore, the potentially relevant genes were verified using RT-qPCR and western blotting. RESULTS: HIST1H2AB was highly expressed in lung adenocarcinoma tissues from TCGA database and immunohistochemistry staining. Similar results were seen in the lung adenocarcinoma cells. When the cells were successfully transfected with shHIST1H2AB or an empty plasmid, downregulation of HIST1H2AB inhibited the growth and promoted the apoptosis of lung adenocarcinoma cells. The xenograft results suggested that HIST1H2AB downregulation delayed tumor growth and reduced tumor weight. Moreover, interferon signaling pathway and four genes (HMGB1, FOXM1, F2RL1 and SLC4A7) might be regulated by HIST1H2AB in the development of lung adenocarcinoma as indicated through gene expression array, RT-qPCR and western blotting analyses. CONCLUSIONS: HIST1H2AB acts as an oncogenic protein and HIST1H2AB inhibition suppresses the proliferation of lung adenocarcinoma cells. It may be a novel target for lung adenocarcinoma therapy.

ERECTA1 Acts Upstream of the OsMKKK10-OsMKK4-OsMPK6 Cascade to Control Spikelet Number by Regulating Cytokinin Metabolism in Rice.

Grain number is a flexible trait that strongly contributes to grain yield. In rice (Oryza sativa), the OsMKKK10-OsMKK4-OsMPK6 cascade, which is negatively regulated by the dual-specificity phosphatase GSN1, coordinates the trade-off between grain number and grain size. However, the specific components upstream and downstream of the GSN1-MAPK module that regulate spikelet number per panicle remain obscure. Here, we report that ERECTA1 (OsER1), a negative regulator of spikelet number per panicle, acts upstream of the OsMKKK10-OsMKK4-OsMPK6 cascade and that the OsER1-OsMKKK10-OsMKK4-OsMPK6 pathway is required to maintain cytokinin homeostasis. OsMPK6 directly interacts with and phosphorylates the zinc finger transcription factor DST to enhance its transcriptional activation of CYTOKININ OXIDASE2 (OsCKX2), indicating that the OsER1-OsMKKK10-OsMKK4-OsMPK6 pathway shapes panicle morphology by regulating cytokinin metabolism. Furthermore, overexpression of either DST or OsCKX2 rescued the spikelet number phenotype of the oser1, osmkkk10, osmkk4, and osmpk6 mutants, suggesting that the DST-OsCKX2 module genetically functions downstream of the OsER1-OsMKKK10-OsMKK4-OsMPK6 pathway. These findings reveal specific crosstalk between a MAPK signaling pathway and cytokinin metabolism, shedding light on how developmental signals modulate phytohormone homeostasis to shape the inflorescence.

Detection and genetic analysis of porcine circovirus-like virus in pigs with diarrhea between 2016 and 2021 in Henan and Shanxi provinces of China.

Porcine circovirus-like virus (PCLV) is a recently discovered virus that may be associated with diarrhea in pigs. To investigate the epidemic profile and genetic characteristics of this virus, 175 clinical samples (141 intestinal samples, 17 blood samples, and 17 fecal samples) were collected from diseased piglets during outbreaks of diarrhea from 33 pig farms in 19 cities of Henan and Shanxi provinces of China between 2016 and 2021 and were screened by PCR for the presence of PCLV. The results showed that the positive rate for PCLV was 32% (56/175) at the sample level, 60.6% (20/33) at the farm level, and 57.9% (11/19) at the city level, which varied from 5.88% to 44.12% between 2016 and 2021. It was also found that PCLV occurred in coinfections with porcine circovirus type 2 (PCV2), PCV3, PCV4, porcine epidemic diarrhea virus, and porcine reproductive and respiratory syndrome virus, but no nucleic acids were detected for transmissible gastroenteritis virus, porcine deltacoronavirus, or porcine rotavirus in piglets with diarrhea. Notably, PCLV was detected in 13 diarrheal piglets from four different farms that were negative for the other porcine viruses. These findings suggest that PCLV may be associated with porcine diarrhea and that it has been circulating in piglets in Henan and Shanxi provinces of China. In addition, the complete genomes of 13 PCLV strains were sequenced and found to share 35.4%-91.0% nucleotide sequence identity with sequences available in the GenBank database. Phylogenetic analysis based on Rep amino acid sequences revealed that the 13 PCLV strains from this study clustered in group 1 and were closely related to eight Chinese PCLV strains, Bo-Circo-like virus CH, American strains 21 and 22, and Hungarian strains 288_4 and 302_4, but they differed genetically from seven other foreign PCLV strains. The whole genome and rep gene of 13 PCLV strains in this study were 72.2%-82% and 83.8%-89.7% identical, respectively, to those of Bo-Circo-like virus strain CH, indicating that PCLV is a novel virus in pigs that may be involved in cross-species transmission. Evidence of a recombination event was found in the rep region of the 13 PCLV strains sequenced. This study enriches the epidemiological data on PCLV infection in pigs in China and lays a foundation for further study on the pathogenesis of PCLV.

Simultaneous detection and phylogenetic analysis of porcine epidemic diarrhea virus and porcine circovirus 4 in Henan province, China.

Porcine circovirus 4 (PCV4) is a recently discovered circovirus that was first reported in 2019 in several pigs in Hunan province of China and has also been identified in pigs infected with porcine epidemic diarrhea virus (PEDV). To further investigate the coinfection and genetic diversity of these two viruses, 65 clinical samples (including feces and intestinal tissues) were collected from diseased piglets on 19 large-scale pig farms in Henan province of China, and a duplex SYBR Green I-based quantitative real-time polymerase chain reaction (qPCR) assay was developed for detecting PEDV and PCV4 simultaneously. The results showed that the limit of detection was 55.2 copies/µL and 44.1 copies/µL for PEDV and PCV4, respectively. The detection rate for PEDV and PCV4 was 40% (26/65) and 38% (25/65), respectively, and the coinfection rate for the two viruses was 34% (22/65). Subsequently, the full-length spike (S) gene of eight PEDV strains and a portion of the genome containing the capsid (Cap) gene of three PCV4 strains were sequenced and analyzed. Phylogenetic analysis showed that all of the PEDV strains from the present study clustered in the G2a subgroup and were closely related to most of the PEDV reference strains from China from 2011 to 2021, but they differed genetically from a vaccine strain (CV777), a Korean strain (virulent DR1), and two Chinese strains (SD-M and LZC). It is noteworthy that two PEDV strains (HEXX-24 and HNXX-24XIA) were identified in one sample, and the HNXX-24XIA strain had a large deletion at amino acids 31-229 of the S protein. Moreover, a recombination event was observed in strain HEXX-24. Phylogenetic analysis based on the amino acid sequence of the PCV4 Cap protein revealed that PCV4 strains were divided into three genotypes: PCV4a1, PCV4a2, and PCV4b. Three strains in the present study belonged to PCV4a1, and they had a high degree of sequence similarity (>98% identity) to other PCV4 reference strains. This study not only provides technical support for field investigation of PEDV and PCV4 coinfection but also provides data for their prevention and control.

Construction of Models To Predict the Effectiveness of E-Waste Control through Capture of Volatile Organic Compounds and Metals/Metalloids Exposure Fingerprints: A Six-Year Longitudinal Study.

The significant health implications of e-waste toxicants have triggered the global tightening of regulation on informal e-waste recycling sites (ER) but with disparate governance that requires effective monitoring. Taking advantage of the opportunity to implement e-waste control in the Guiyu ER since 2015, we investigated the temporal variations in levels of oxidative DNA damage, 25 volatile organic compound metabolites (VOCs), and 16 metals/metalloids (MeTs) in urine in 918 children between 2016 and 2021 to demonstrate the effectiveness of e-waste control in reducing population exposure risks. The hazard quotients of most MeTs and levels of 8-hydroxy-2'-deoxyguanosine in children decreased significantly during this time, indicating that e-waste control effectively reduces the noncarcinogenic risks of MeT exposure and levels of oxidative DNA damage. Using mVOC-derived indexes as a feature, a bagging-support vector machine algorithm-based machine learning model was constructed to predict the extent of e-waste pollution (EWP). The model exhibited excellent performance with accuracies >97.0% in differentiating between slight and severe EWP. Five simple functions established using mVOC-derived indexes also had high accuracy in predicting the presence of EWP. These models and functions provide a novel human exposure monitoring-based approach for assessing e-waste governance or the presence of EWP in other ERs.

Why Do People Gain Belly Fat in Rural Areas? A Study of Urinary Metal(loid)s and Abdominal Obesity in China.

Obesity is prevalent in rural areas of China, and there are inconsistent findings regarding the association between metal(loid) exposure and the risk of obesity. Abdominal obesity (AOB), which reflects visceral fat abnormity, is a crucial factor in studying obesity-related diseases. We conducted a study measuring 20 urinary metal(loid)s, 13 health indicators, and the waist circumference (WC) in 1849 participants from 10 rural areas of China to investigate their relationships. In the single exposure models, we found that urinary chromium (Cr) was significantly associated with the odds of having AOB [adjusted odds ratio (OR) = 1.81 (95% confidence interval (CI): 1.24, 2.60)]. In the mixture exposure models, urinary Cr consistently emerged as the top contributor to AOB, while the overall effect of mixed metal(loid)s was positive toward the odds of having AOB [adjusted OR: 1.33 (95% CI: 1.00, 1.77)], as revealed from the quantile g-computation model. After adjusting for the effects of other metal(loid)s, we found that the elevation of apolipoprotein B and systolic blood pressure significantly mediated the association between urinary Cr and the odds of having AOB by 9.7 and 19.4%, respectively. Our results suggest that exposure to metal(loid)s is a key factor contributing to the prevalence of AOB and WC gain in rural areas of China.

Mapping single-nucleotide m6A by m6A-REF-seq.

The past few years have witnessed rapid progress in the field of RNA modifications. As the most prevailing modification on eukaryotic mRNA, m6A is characterized to play a vital role in various cellular activities. However, limitations of the detection method impede functional studies of m6A. Here we introduce m6A-REF-seq, a powerful and straightforward method to identify m6A at single-nucleotide resolution. m6A-REF-seq relies on the recognition of RNA endonuclease MazF towards m6A at the ACA motif, providing an orthogonal method independent of the m6A antibody being adopted by most of current methods. We describe a detailed protocol to perform m6A-REF-seq, including NGS library construction and sequencing data analysis. In particular, we describe an optimized assay to validate individual m6A sites identified by m6A-REF-seq, which can also be applied to detect any candidate m6A sites.

Relationship between serum CHIP levels with cardiovascular disease in maintenance haemodialysis patients.

Many preclinical studies reported that the carboxyl terminus of Hsp70-interacting protein (CHIP) has cardiovascular protective effects. This study was designed to explore whether CHIP is related with cardiovascular disease (CVD) in maintanence haemodialysis (MHD) patients. 217 MHD patients and 150 healthy controls were recruited, serum CHIP concentration and clinical characteristics were measured. MHD patients were followed-up for 36 months and their cardiovascular events (CVEs) and survival conditions were recorded. Here, the data shows that serum CHIP concentrations in MHD patients were lower than those in healthy controls (31.69 ± 18.2 pg/mL vs 84.53 ± 22.1 pg/mL, p < 0.05). CHIP negatively correlated with age, C-reactive protein, B-type brain natriuretic peptide, phosphorus, parathyroid hormone, carotid intima-media thickness (CIMT) and left ventricular septal thickness (LVSTd), whereas it positively associated with albumin, haemoglobin, creatinine, Kt/V and ejection fraction (p < 0.05, respectively). Partial correlation and multiple linear regression analysis verified the negative relationship between CHIP with CIMT or LVSTd (p < 0.05, respectively). Using quartile method and Kaplan-Meier survival function, it indetified that the lower serum CHIP concentration predicted risk of CVEs, CVD and all-cause death (p < 0.001). Cox regression analysis manifested CHIP was negatively associated with CVEs (HR = 0.914, 95%CI 0.880-0.950, p < 0.001), CVD mortality (HR = 0.747, 95%CI 0.651-0.857, p < 0.001) and all-cause death (HR = 0.769, 95%CI 0.696-0.850, p < 0.001). In conclusion, the data of this study revealed that serum CHIP level is significantly correlated with multiple risk factors of CVD and may be one of the predictors of CVD risk and death in MHD patients.

[Analysis of minimally invasive treatment in the management of prostatic abscess].

OBJECTIVE: To analyze the proper time and method for treatment of prostatic abscess (PA). METHODS: This is a retrospective study that included 18 patients diagnosed with and treated for prostatic abscess between February 2017 and July 2022. After obtaining data from the patients' medical records, we analyzed their clinical features as well as the therapeutic methods opted for and their effectiveness. Results： Of the 18 patients included, one achieved a full recovery after a spontaneous rupture of the abscess. Transrectal ultrasound (TRUS)-guided aspiration was performed in the remaining 17 patients, of whom 14 had a complete resolution after this procedure whereas 3 experienced recurrence. The recurrent cases were successfully managed with transurethral (TU) de-roofing. CONCLUSION: TRUS-guided aspiration is a treatment modality with a marked curative effect for simple PAs. For refractory abscesses (recurrent, multifocal, incomplete or unsuccessful drainage) or PA located near the urethra, TU de-roofing can be considered as a first choice to shorten the course of the disease and alleviate the medical treatment expenses due to recurrence.

Characterization of a bifunctional and endolytic alginate lyase from Microbulbifer sp. ALW1 and its application in alginate oligosaccharides production from Laminaria japonica.

The diverse biological activities of alginate oligosaccharides attracted extensive exploration of alginate lyases with various substrate specificity and enzymatic properties. In this study, an alginate lyase from Microbulbifer sp. ALW1, namely AlgL7, was phylogenetically classified into the polysaccharide lyase family 7 (PL7). The conserved amino acid residues Tyr606 and His499 in AlgL7 were predicted to act as the general acid/base catalysts. The enzyme was enzymatically characterized after heterologous expression and purification in E. coli. AlgL7 displayed optimal activity at 40 °C and pH 7.0. It had good stability at temperature below 35 °C and within a pH range of 5.0-10.0. AlgL7 exhibited good stability against the reducing reagent ß-ME and the surfactants of Tween-20 and Triton X-100. The degradation profiles of alginate indicated AlgL7 was a bifunctional endolytic alginate lyase generating alginate oligosaccharides with the degrees of polymerization 2-4. The degradation products of sodium alginate exhibited stronger antioxidant activities than the untreated polysaccharide. In addition, AlgL7 could directly digest Laminaria japonica to produce alginate oligosaccharides. These characteristics of AlgL7 offer a great potential of its application in high-value utilization of brown algae resources.

Characterization of a bioactive meroterpenoid isolated from the marine-derived fungus Talaromyces sp.

A new meroterpenoid, taladrimanin A (1), was isolated from a marine-derived fungus Talaromyces sp. HM6-1-1, together with eleven biogenetically related compounds (2-12). A plausible biosynthetic pathway for the meroterpenoids (1-4) was proposed. The planar structure of 1 was assigned by HRESIMS and NMR. Its relative configuration was established by quantum chemical NMR calculation of two possible isomers and analyzed by DP4 + method. Finally, X-ray diffraction unambiguously confirmed the relative configuration and revealed the absolute configuration of compound 1. 2-12 were assigned by comparing their NMR data with those reported in the literature. 1 was the first drimane-type meroterpenoid with a C10 polyketide unit bearing an 8R-configuration. In the bioactive assay, 1 exhibited antitumor activity against gastric cancer cells MGC803 and MKN28; it also inhibited the colony formation and induced apoptosis in MGC803 cells both in a concentration-dependent manner. Additionally, 1 displayed selective antibacterial activity against Staphylococcus aureus 6538P, and low activities towards strains of Vibrio parahaemolyticus and Escherichia coli in this study. KEY POINTS: • Twelve compounds were obtained from Talaromyces sp., including four meroterpenoids, one of which was new. • The new compound taladrimanin A (1) inhibits the growth of gastric cancer cells MGC803 and MKN28 as well as the pathogenic bacteria Staphylococcus aureus 6538P. • The biosynthetic pathway of the meroterpenoids was proposed.

Peripheral Tumor Location Predicts a Favorable Prognosis in Patients with Resected Small Cell Lung Cancer.

Background: Small cell lung cancer (SCLC) is an aggressive malignancy. Surgical resection is currently only recommended for clinical stage I patients who have been carefully staged. The clinical outcomes of patients with resected SCLCs vary because the disease is highly heterogeneous, suggesting that selected patients could be considered for surgical resection depending on their clinical and/or molecular characteristics. Methods: We collected data on a retrospective cohort of 119 limited-stage SCLC patients who underwent lobectomy with mediastinal lymph node dissection from March 2013 to March 2020 at Harbin Medical University Cancer Hospital. Correlations were derived using Fisher's exact test. Models of 2-year and 3-year survival were evaluated by deriving the area under receiver operating characteristic curves. Kaplan-Meier and Cox regression analyses were used to evaluate significant differences between the survival curves and hazard ratios. Results: The median disease-free survival (DFS) was 35.9 months (range 0.9-105.3 months), and the median overall survival (OS) was 45.2 months (range 4.8-105.3 months). Univariate analysis showed that TNM stage was significantly correlated with DFS and OS. The 2-year disease-free rates of patients with stage I, II, and III disease were 76.4%, 50.5%, and 36.1%, respectively, and the 3-year OS rates were 75.9%, 57.7%, and 34.4%, respectively. In pN + patients, multiple (or multiple-station) lymph node involvement significantly increased recurrence and reduced survival compared with patients with single or single-station metastases. Patients with peripheral SCLCs evidenced significantly better DFS and OS than did patients with central tumors. Multivariate analysis showed that TNM stage and tumor location were independently prognostic in Chinese patients with resected limited-stage SCLC. A combination of TNM stage and tumor location was helpful for prognosis. Conclusions: TNM stage and tumor location were independently prognostic in Chinese patients with resected SCLCs. Patient stratification by tumor location should inform the therapeutic strategy. The role of surgical resection for limited-stage SCLC patients must be reevaluated, as this may be appropriate for some patients.