Recent advances and role of melatonin in post-harvest quality preservation of shiitake (Lentinula edodes).

Shiitake mushrooms are renowned for their popularity and robust nutritional value, are susceptible to spoilage due to their inherent biodegradability. Nevertheless, because of their lack of protection, these mushrooms have a short shelf life. Throughout the post-harvest phase, mushrooms experience a persistent decline in quality. This is evidenced by changes such as discoloration, reduced moisture content, texture changes, an increase in microbial count, and the depletion of nutrients and flavor. Ensuring postharvest quality preservation and prolonging mushroom shelf life necessitates the utilization of post-harvest preservation techniques, including physical, chemical, and thermal processes. This review provides a comprehensive overview of the deterioration processes affecting mushroom quality, covering elements such as moisture loss, discoloration, texture alterations, increased microbial count, and the depletion of nutrients and flavor. It also explores the key factors influencing these processes, such as temperature, relative humidity, water activity, and respiration rate. Furthermore, the review delves into recent progress in preserving mushrooms through techniques such as drying, cooling, packaging, irradiation, washing, and coating.

Adjuvant Chemotherapy in Premenopausal Patients With Hormone-Positive Breast Cancer With a Recurrence Score of 16-25: A Retrospective Analysis Using the National Cancer Database.

PURPOSE: Results from the TAILORx trial revealed that the use of adjuvant chemotherapy along with endocrine therapy had no survival advantage in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2-negative (HER2-), node-negative (N0) breast cancer (BC) with an intermediate (11-25) 21-gene recurrence score (RS) in the overall population. However, in patients under age 50 years, adjuvant chemotherapy demonstrated a progression-free survival benefit when the RS ranged from 16-25. We studied this cohort with the population-based national database. METHODS: The 2010-2018 National Cancer Database was used to include patients with BC age 18-50 years, N0, M0, RS 16-25, ER+/progesterone receptor±, and HER2-. Patients were divided into two groups on the basis of adjuvant chemotherapy use, and the survival between them was compared. RESULTS: Adjuvant chemotherapy use was noted in 4,808/15,792 (30.45%) patients. Median RS was 18 and 21 in patients without and with adjuvant chemotherapy, respectively. Factors associated with adjuvant chemotherapy use were higher T stage, poor and moderately differentiated tumors, age <40 years, care at an academic center, Caucasian race, patients undergoing mastectomy, regional lymph node surgery, and radiation therapy. Kaplan-Meier survival at 10 years was better with adjuvant chemotherapy (96.2% v 91.6%). Patients without adjuvant chemotherapy had more adverse outcomes (hazard ratio [HR], 1.683 [95% CI, 1.392 to 2.036]; P < .0001). Subgroup analysis showed that the benefit was significant in patients with RS scores 21-25 (HR, 1.953 [95% CI, 1.295 to 2.945]), ductal histology (HR, 1.521 [95% CI, 1.092 to 2.118]), Caucasian race (HR, 1.655 [95% CI, 1.180 to 2.322]), and 41-50 years age group (HR, 1.732 [95% CI, 1.244 to 2.411]). CONCLUSION: Our study showed an overall survival benefit for adjuvant chemotherapy use in patients with ER-positive, N0 premenopausal BC patients, age less than 50 years, with an intermediate RS score, particularly 21-25.

Intraocular mRNA delivery with endogenous MmPEG10-based virus-like particles.

Virus-like particles (VLP) are a promising tool for intracellular gene delivery, yet their potential in ocular gene therapy remains underexplored. In this study, we bridged this knowledge gap by demonstrating the successful generation and application of vesicular stomatitis virus glycoprotein (VSVG)-pseudotyped mouse PEG10 (MmPEG10)-VLP for intraocular mRNA delivery. Our findings revealed that PEG10-VLP can efficiently deliver GFP mRNA to adult retinal pigment epithelial cell line-19 (ARPE-19) cells, leading to transient expression. Moreover, we showed that MmPEG10-VLP can transfer SMAD7 to inhibit epithelial-mesenchymal transition (EMT) in RPE cells effectively. In vivo experiments further substantiated the potential of these vectors, as subretinal delivery into adult mice resulted in efficient transduction of retinal pigment epithelial (RPE) cells and GFP reporter gene expression without significant immune response. However, intravitreal injection did not yield efficient ocular expression. We also evaluated the transduction characteristics of MmPEG10-VLP following inter-cameral delivery, revealing transient GFP protein expression in corneal endothelial cells without significant immunotoxicities. In summary, our study established that VSVG pseudotyped MmPEG10-based VLP can transduce mitotically inactive RPE cells and corneal endothelial cells in vivo without triggering an inflammatory response, underscoring their potential utility in ocular gene therapy.

The Development of Serrated Epithelial Change in Ulcerative Colitis is not Significantly Associated with Increased Histologic Inflammation.

Serrated epithelial change (SEC) in inflammatory bowel disease is most often defined as hyperplastic polyp-like mucosal change detected on random biopsies. Although SEC has been reported to be associated with an increased risk of synchronous and/or metachronous colorectal neoplasia, it remains unknown if SEC represents a form of dysplastic lesion despite the lack of morphologic evidence of dysplasia. Since the risk of colorectal neoplasia in ulcerative colitis (UC) is positively correlated with increased histologic inflammation, this study investigated if increased colonic inflammation is an independent risk factor for SEC. A cohort of 28 UC patients with SEC was analyzed and compared with 51 control UC patients without SEC. None of these patients had a history of colorectal neoplasia. For each patient with SEC, all biopsies conducted before and at the time of SEC diagnosis (versus all biopsies for each control patient) were scored by using a 4-point scoring system: no activity (no epithelial infiltration by neutrophils=0); mild activity (cryptitis only=1); moderate activity (cryptitis plus crypt abscess formation in <50% of crypts=2); and severe activity (crypt abscess formation in ≥50% of crypts, erosion, neutrophilic exudate, and/or ulceration=3). Each biopsy was designated a score, and both mean and maximum inflammation scores were calculated from all biopsies taken during each colonoscopy. The inflammation burden score was calculated for each surveillance interval by multiplying the average maximum score between each pair of surveillance episodes by the length of the surveillance interval in years. The average scores of all colonoscopies for each patient were used to assign the patient's overall mean, maximum, and inflammation burden scores. The SEC cohort included 12 (43%) men and 16 (57%) women with a mean age of 47 years at the time of the first SEC diagnosis and a long history of UC (mean: 13 y). The majority of patients (n=21; 75%) had pancolitis, and only 1 (4%) patient had primary sclerosing cholangitis. A total of 37 SEC were identified in the 28 patients, 4 (14%) of whom had multifocal SEC. SEC was predominantly found in the left colon (n=32; 86%). In the multivariate analysis, none of the 3 summative inflammation scores, including overall mean (odds ratio [OR] 1.9, P=0.489), maximum (OR 0.4, P=0.259), and inflammation burden scores (OR 1.2, P=0.223), were significantly associated with the development of SEC. Similarly, no other potential risk factors, including age, gender, ethnicity, and duration and extent of UC, were significantly correlated with the detection of SEC (P>0.05). In conclusion, the development of SEC in UC is not significantly associated with increased histologic inflammation. Given the reported association of SEC with an increased risk of synchronous and/or metachronous colorectal neoplasia, along with the presence of molecular alterations in some cases (such as TP53 mutations and aneuploidy), SEC may represent an early morphologic indicator of segmental or pan-colonic molecular abnormalities that have not advanced enough to result in colorectal neoplasia, as opposed to being a form of dysplasia.

Expert consensus on Prospective Precision Diagnosis and Treatment Strategies for Osteoporotic Fractures.

Osteoporotic fractures are the most severe complications of osteoporosis, characterized by poor bone quality, difficult realignment and fixation, slow fracture healing, and a high risk of recurrence. Clinically managing these fractures is relatively challenging, and in the context of rapid aging, they pose significant social hazards. The rapid advancement of disciplines such as biophysics and biochemistry brings new opportunities for future medical diagnosis and treatment. However, there has been limited attention to precision diagnosis and treatment strategies for osteoporotic fractures both domestically and internationally. In response to this, the Chinese Medical Association Orthopaedic Branch Youth Osteoporosis Group, Chinese Geriatrics Society Geriatric Orthopaedics Committee, Chinese Medical Doctor Association Orthopaedic Physicians Branch Youth Committee Osteoporosis Group, and Shanghai Association of Integrated Traditional Chinese and Western Medicine Osteoporosis Professional Committee have collaborated to develop this consensus. It aims to elucidate emerging technologies that may play a pivotal role in both diagnosis and treatment, advocating for clinicians to embrace interdisciplinary approaches and incorporate these new technologies into their practice. Ultimately, the goal is to improve the prognosis and quality of life for elderly patients with osteoporotic fractures.

Hypoxic Exosomal circPLEKHM1-Mediated Crosstalk between Tumor Cells and Macrophages Drives Lung Cancer Metastasis.

Intercellular communication often relies on exosomes as messengers and is critical for cancer metastasis in hypoxic tumor microenvironment. Some circular RNAs (circRNAs) are enriched in cancer cell-derived exosomes, but little is known about their ability to regulate intercellular communication and cancer metastasis. Here, by systematically analyzing exosomes secreted by non-small cell lung cancer (NSCLC) cells, a hypoxia-induced exosomal circPLEKHM1 is identified that drives NSCLC metastasis through polarizing macrophages toward to M2 type. Mechanistically, exosomal circPLEKHM1 promoted PABPC1-eIF4G interaction to facilitate the translation of the oncostatin M receptor (OSMR), thereby promoting macrophage polarization for cancer metastasis. Importantly, circPLEKHM1-targeted therapy significantly reduces NSCLC metastasis in vivo. circPLEKHM1 serves as a prognostic biomarker for metastasis and poor survival in NSCLC patients. This study unveils a new circRNA-mediated mechanism underlying how cancer cells crosstalk with macrophages within the hypoxic tumor microenvironment to promote metastasis, highlighting the importance of exosomal circPLEKHM1 as a prognostic biomarker and therapeutic target for lung cancer metastasis.

[Expert consensus on integrated traditional Chinese and western medicine diagnosis and treatment for osteoporotic fractures].

Osteoporotic fractures represent the most severe complications of osteoporosis,characterized by insidious onset,high mortality and disability rates,and a steadily increasing incidence,imposing a significant socioeconomic burden. Western medicine has advantages in diagnosis and surgical interventions,while traditional Chinese medicine excels in holistic management and the restoration of bodily equilibrium. The integration of both traditional Chinese medicine (TCM) and western medicine emerges as an effective therapeutic strategy for osteoporotic fractures. In order to propagate the concept of integrated diagnosis and treatment,foster the advancement of integrated medical techniques for osteoporotic fractures,and establish standardized and normative protocols for disease prevention,diagnosis,and treatment,a consensus expert group,led by Geriatric Branch of Chinese Geriatrics Society,the Young Osteoporosis Group of Orthopedics Branch of Chinese Medical Association,Osteoporosis Group of Orthopedics Branch of Chinese Physician Association,and Osteoporosis Professional Committee of the Shanghai Society of Integrated Traditional Chinese and Western Medicine,was established. This group engaged in deliberations and formulated the "Expert Consensus on Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Osteoporotic Fractures" elucidating the concept of integrated medicine and offering recommendations in the domains of prevention,diagnosis,and treatment,with the aspiration of ameliorating the prognosis of osteoporotic fractures and enhancing the quality of life for these patients.

CD169+ classical monocyte as an important participant in Graves' ophthalmopathy through CXCL12-CXCR4 axis.

Patients with Graves' disease (GD) can develop Graves' ophthalmopathy (GO), but the underlying pathological mechanisms driving this development remain unclear. In our study, which included patients with GD and GO, we utilized single-cell RNA sequencing (scRNA-seq) and multiplatform analyses to investigate CD169+ classical monocytes, which secrete proinflammatory cytokines and are expanded through activated interferon signaling. We found that CD169+ clas_mono was clinically significant in predicting GO progression and prognosis, and differentiated into CD169+ macrophages that promote inflammation, adipogenesis, and fibrosis. Our murine model of early-stage GO showed that CD169+ classical monocytes accumulated in orbital tissue via the Cxcl12-Cxcr4 axis. Further studies are needed to investigate whether targeting circulating monocytes and the Cxcl12-Cxcr4 axis could alleviate GO progression.

A multifunctional composite hydrogel that sequentially modulates the process of bone healing and guides the repair of bone defects.

Calcium carbonate (CaCO3), which exhibits excellent biocompatibility and bioactivity, is a well-established bone filling material for bone defects. Here, we synthesized CaCO3microspheres (CMs) to use as an intelligent carrier to load bone morphogenetic protein-2 (BMP-2). Subsequently, drug-loaded CMs and catalase (CAT) were added to methacrylated gelatin (GelMA) hydrogels to prepare a composite hydrogel for differential release of the drugs. CAT inside hydrogels was released with a fast rate to eliminate H2O2and generate oxygen. Constant BMP-2 release from CMs induced rapid osteogenesis. Resultsin vitroindicated that the composite hydrogels efficiently reduced the level of intracellular reactive oxygen species, preventing cells from being injured by oxidative stress, promoting cell survival and proliferation, and enhancing osteogenesis. Furthermore, animal experiments demonstrated that the composite hydrogels were able to inhibit the inflammatory response, regulate macrophage polarization, and facilitate the healing of bone defects. These findings indicate that a multi-pronged strategy is greatly expected to promote the bone healing by modulating pathological microenvironments.

DADS Inhibits the Proliferation of MDCC-MSB-1 Cells by Inducing Autophagy via the MEK/ERK Signalling Pathway.

Diallyl disulfide (DADS) is effective at suppressing tumour cell growth and proliferation. This study verified the morphology and growth activity of MDCC-MSB-1 cells by using an MTT assay to detect the effect of DADS on the proliferation of MDCC-MSB-1 cells and a CCK8 assay to detect the effect of DADS on the viability and proliferation of MDCC-MSB-1 cells. We found that the viability and proliferation of MDCC-MSB-1 cells decreased with increasing DADS concentrations. MDC staining and Western blotting were used to analyse autophagy, the associated protein LC3 and the MEK/ERK pathway proteins MEK and ERK and to investigate changes in cellular autophagy based on cell morphology and molecular biology. With increasing concentrations of DADS, MDCC-MSB-1 cell autophagy increased in a gradient manner. Additionally, the conversion of the autophagy marker protein LC3-I increased with increasing drug concentrations, and the relative expression of LC3-II steadily increased, as did the expression of key protein components of the MEK/ERK signalling pathway, including P-MEK1/2 and P-ERK1/2. These results suggest that DADS induces autophagy through the MEK/ERK pathway, thereby inhibiting the proliferation of MDCC-MSB-1 cells.

A five-year quasi-experimental study to evaluate the impact of empiric antibiotic order sets on antibiotic use metrics among hospitalized adult patients.

OBJECTIVE: Evaluation of adult antibiotic order sets (AOSs) on antibiotic stewardship metrics has been limited. The primary outcome was to evaluate the standardized antimicrobial administration ratio (SAAR). Secondary outcomes included antibiotic days of therapy (DOT) per 1,000 patient days (PD); selected antibiotic use; AOS utilization; Clostridioides difficile infection (CDI) cases; and clinicians' perceptions of the AOS via a survey following the final study phase. DESIGN: This 5-year, single-center, quasi-experimental study comprised 5 phases from 2017 to 2022 over 10-month periods between August 1 and May 31. SETTING: The study was conducted in a 752-bed tertiary care, academic medical center. INTERVENTION: Our institution implemented AOSs in the electronic medical record (EMR) for common infections among hospitalized adults. RESULTS: For the primary outcome, a statistically significant decreases in SAAR were detected from phase 1 to phase 5 (1.0 vs 0.90; P < .001). A statistically significant decreases were detected in DOT per 1,000 PD (4,884 vs 3,939; P = .001), fluoroquinolone orders (407 vs 175; P < .001), carbapenem orders (147 vs 106; P = .024), and clindamycin orders (113 vs 73; P = .01). No statistically significant change in mean vancomycin orders was detected (991 vs 902; P = .221). A statistically significant decrease in CDI cases was also detected (7.8, vs 2.4; P = .002) but may have been attributable to changes in CDI case diagnosis. Clinicians indicated that the AOSs were easy to use overall and that they helped them select the appropriate antibiotics. CONCLUSIONS: Implementing AOS into the EMR was associated with a statistically significant reduction in SAAR, antibiotic DOT per 1,000 PD, selected antibiotic orders, and CDI cases.

METTL3 promotes microglial inflammation via MEF2C in spinal cord injury.

Spinal cord injury (SCI) is a significant contributor to disability in contemporary society, resulting in substantial psychological and economic burdens for patients and their family. Microglia-mediated inflammation is an important factor affecting the nerve repair of SCI patients. N6-methyladenosine (m6A) is a prevalent epigenetic modification in mammals, which shows a strong association with inflammation. However, the mechanism of m6A modification regulating microglia-mediated inflammation is still unclear. Here, we observed that METTL3, a m6A methylase, was increased in SCI mice and lipopolysaccharide (LPS)-exposed BV2 cells. Knockdown of METTL3 inhibited the increased expression of iNOS and IL-1ß induced by LPS in vitro. Subsequently, MEF2C, myocyte-specific enhancer factor 2C, was decreased in SCI mice and LPS-exposed BV2 cells. Knockdown of MEF2C promoted the expression of iNOS and IL-1ß. Sequence analysis showed that there were multiple highly confident m6A modification sites on the MEF2C mRNA. METTL3 antibody could pull down a higher level of MEF2C mRNA than the IgG in RNA binding protein immunoprecipitation assay. Knockdown of METTL3 promoted MEF2C protein expression and MEF2C mRNA expression, accompanied by a reduced m6A modification level on the MEF2C mRNA. Knockdown of MEF2C inhibited the anti-inflammatory effect of METTL3 siRNA. Our results suggest that METTL3 promotes microglia inflammation via regulating MEF2C mRNA m6A modification induced by SCI and LPS treatment.

Type I BREX system defends against antibiotic-resistant plasmids in Escherichia coli.

The Bacteriophage Exclusion (BREX) system is a novel antiphage defense system identified in Bacillus cereus in 2015. The purpose of this study was to investigate the presence of the BREX system defenses against antibiotic-resistant plasmids such as blaKPC and blaNDM invasion in Escherichia coli. The BREX system was present in 5.4% (23/424) of E. coli clinical isolates and 6.5% (84/1283) of E. coli strains with completely sequenced genomes in the GenBank database. All 23 BREX-positive E. coli clinical isolates were susceptible to carbapenems, while all five isolates carrying blaKPC and 11 carrying blaNDM were BREX-negative. For E. coli strains in the GenBank database, 37 of 38 strains carrying blaKPC and 109 of 111 strains carrying blaNDM were BREX negative. The recognition site sequence of methyltransferase PglX in a clinical E. coli 3756 was 5'-CANCATC-3' using PacBio single-molecular real-time sequencing. The transformation efficiency of plasmid psgRNA-ColAori-target with the PglX recognition site was reduced by 100% compared with the plasmid without the recognition site in E. coli DH5α-pHSG398-BREX. The BREX showed lower defense efficacy against plasmid psgRNA-15Aori-target which had the same plasmid backbone but different surrounding sequences of recognition sites with psgRNA-ColAori-target. The conjugation frequency of the KPC-2 plasmid and NDM-5 plasmid in E. coli 3756-ΔBREX was higher than that in E. coli 3756 clinical isolate (1.0 × 10-6 vs 1.3 × 10-7 and 5.5 × 10-7 vs 1.7 × 10-8, respectively). This study demonstrated that the type I BREX system defends against antibiotic-resistant plasmids in E. coli.

Nonlinear changes in pupillary attentional orienting responses across the lifespan.

The cognitive aging process is not necessarily linear. Central task-evoked pupillary responses, representing a brainstem-pupil relationship, may vary across the lifespan. Thus we examined, in 75 adults ranging in age from 19 to 86, whether task-evoked pupillary responses to an attention task may serve in as an index of cognitive aging. This is because the locus coeruleus (LC), located in the brainstem, is not only among the earliest sites of degeneration in pathological aging, but also supports both attentional and pupillary behaviors. We assessed brief, task-evoked phasic attentional orienting to behaviorally relevant and irrelevant auditory tones, stimuli known specifically to recruit the LC in the brainstem and evoke pupillary responses. Due to potential nonlinear changes across the lifespan, we used a novel data-driven analysis on 6 dynamic pupillary behaviors on 10% of the data to reveal cut off points that best characterized the three age bands: young (19-41 years old), middle aged (42-68 years old), and older adults (69 + years old). Follow-up analyses on independent data, the remaining 90%, revealed age-related changes such as monotonic decreases in tonic pupillary diameter and dynamic range, along with curvilinear phasic pupillary responses to the behaviorally relevant target events, increasing in the middle-aged group and then decreasing in the older group. Additionally, the older group showed decreased differentiation of pupillary responses between target and distractor events. This pattern is consistent with potential compensatory LC activity in midlife that is diminished in old age, resulting in decreased adaptive gain. Beyond regulating responses to light, pupillary dynamics reveal a nonlinear capacity for neurally mediated gain across the lifespan, thus providing evidence in support of the LC adaptive gain hypothesis.

Natural variation in the promoter of FLOWERING LOCUS T-LIKE 2 in pumpkin (Cucurbita moschata Duch.) is associated with flowering time under short-day conditions.

Late flowering is a serious bottleneck in pumpkin (Cucurbita moschata Duch.) agriculture production. Although key genes governing flowering time have been reported in many species, the regulatory network of flowering in pumpkin remains largely obscure, thereby impeding the resolution of industry-wide challenges associated with delayed fruit ripening in pumpkin cultivation. Here, we report an early flowering pumpkin germplasm accession (LXX-4). Using LXX-4 and a late flowering germplasm accession (HYM-9), we constructed an F2 segregation population. A significant difference in FLOWERING LOCUS T-LIKE 2 (FTL2) expression level was identified to be the causal factor of the flowering time trait discrepancy in LXX-4 and HYM-9. Moreover, we have shown that a 21 bp InDel in the FTL2 promoter was the key reason for the waxing and waning of its transcript level. The 21 bp deletion excluded a repressor-AGL19 and recruited activators-BBX7, WRKY40 and SVP to the FTL2 promoter in LXX-4. Together, our data add a useful element to our knowledge which could be used to simplify breeding efforts for early-maturing pumpkin.

Dietary Achievable Dose of Protocatechuic Acid, a Metabolite of Flavonoids, Inhibits High-Fat Diet-Induced Obesity in Mice.

SCOPE: Protocatechuic acid (PCA), a gut microbiota metabolite of flavonoids, inhibits dietary obesity and increases uncoupling protein 1 (UCP1), a critical regulator responsible for adipose thermogenesis; however, these effects are achieved at dietary unachievable (pharmacological) dose. It evaluates whether dietary achievable dose of PCA inhibits adiposity by activating adipose thermogenesis. METHODS AND RESULTS: Six-week-old male C57BL/6J mice are fed a high-fat diet (HFD) alone (control) or supplemented with 0.003% PCA w/w for 16 weeks. PCA consumption does not affect food intake but appreciably reduces body weight gain, improves insulin sensitivity, and attenuates hepatic steatosis. These effects are associated with no significant changes in the abundance of UCP1 in adipose tissues. Instead, PCA consumption increases the abundance and enzymatic activity of carnitine palmitoyltransferase 1 (the first rate-limiting enzyme in fatty acid oxidation) in the livers, inguinal white, and brown adipose tissues. Surprisingly, PCA at physiologically achievable dose does not affect the abundance and enzymatic activity of carnitine acyltransferase-1 expression and the capacity of fatty acid oxidation in 3T3-L1-derived white or brown adipocytes and human hepatoma HepG2 cells. CONCLUSIONS: Dietary achievable dose of PCA attenuates HFD-induced adiposity, which is likely achieved by increasing fatty acid oxidation other than activating adipose thermogenesis.

Psychiatric providers' attitudes toward patients with borderline personality disorder and possible ways to improve them.

OBJECTIVE: Tending to patients with a diagnosis of borderline personality disorder (BPD) is a challenging task for clinicians due to stigma and differences in opinion within the psychiatric community. Various symptoms of BPD including affective instability, mood reactivity, and extremes of idealization are associated with challenging emotions toward patients with BPD. This observational research study utilized an adaptation of the 37-question Attitude to Personality Disorder Questionnaire (APDQ) to assess the attitudes of clinicians toward patients with BPD. METHODS: This questionnaire was distributed to 139 clinicians including psychiatry attendings, psychiatry residents, registered nurses, nurse practitioners, social workers, recreation and art therapists, and psychologists who worked with patients diagnosed with BPD on an inpatient unit. Responses of participants were compared based on occupation, gender, and duration of years worked on an inpatient psychiatric unit. RESULTS: Results show that individuals employed in occupations under the "other health professionals" category had more positive transference (which included feelings of respect toward BPD patients along with feelings of closeness and warmth) toward patients with BPD, and nurses had an increased total score for lack of valid difficulties compared with other health professionals. When grouping by gender and duration of year spent working on an inpatient unit, there were no significant differences in the response toward patients with BPD in affective situations. CONCLUSION: Clinical implications are discussed, as well as the need for training to help improve staff attitudes toward this patient population.

Efficient treatment of old landfill leachate by peroxodisulfate assisted electro-oxidation and electro-coagulation combined system.

Efficient removal of chemical oxygen demand (COD) and ammonium-N (NH4+-N) is the key issue for treatment of old landfill leachate. In this study, a peroxodisulfate assisted electro-oxidation and electro-coagulation coupled system (POCS) adopting Ti/SnO2-Sb2O3/TiO2 and Fe dual-anode was constructed for synergistic removal of COD and NH4+-N in old landfill leachate. Laboratory experiment results showed that with current density of 20 mA cm-2, initial pH value of 8.0 and peroxodisulfate (PDS) concentration of 60 mM, the POCS system can reach removal efficiencies of 84.2% for COD and 39.8% for NH4+-N. The POCS effectively reduced the complexity of macromolecular organics and avoided the need to add acid or base to adjust pH value. The residual NH4+-N could be effectively recovered through struvite precipitation with a 93.8% purity of the precipitate.

Identification of Crucial Genes and Signaling Pathways in Alectinib-Resistant Lung Adenocarcinoma Using Bioinformatic Analysis.

Alectinib, a second-generation anaplastic lymphoma kinase (ALK) inhibitor, has been shown to be effective for patients with ALK-positive non-small cell lung cancer (NSCLC). However, alectinib resistance is a serious problem worldwide. To the best of our knowledge, little information is available on its molecular mechanisms using the Gene Expression Omnibus (GEO) database. In this study, the differentially expressed genes (DEGs) were selected from the gene expression profile GSE73167 between parental and alectinib-resistant human lung adenocarcinoma (LUAD) cell samples. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) annotation enrichment analyses were conducted using Database for Annotation, Visualization and Integrated Discovery (DAVID). The construction of protein-protein interaction (PPI) network was performed to visualize DEGs. The hub genes were extracted based on the analysis of the PPI network using plug-in cytoHubba of Cytoscape software. The functional roles of the key genes were investigated using Gene Expression Profiling Interactive Analysis (GEPIA), University of Alabama at Birmingham Cancer (UALCAN), Gene Set Enrichment Analysis (GSEA), and Tumor Immune Estimation Resource (TIMER) analysis. The networks of kinase, miRNA, and transcription-factor targets of SFTPD were explored using LinkedOmics. The drug sensitivity analysis of SFTPD was analyzed using the RNAactDrug database. Results showed a total of 144 DEGs were identified. Five hub genes were extracted, including mucin 5B (MUC5B), surfactant protein D (SFTPD), deleted in malignant brain tumors 1 (DMBT1), surfactant protein A2 (SFTPA2), and trefoil factor 3 (TFF3). The survival analysis using GEPIA displayed that low expression of SFTPD had a significantly negative effect on the prognosis of patients with LUAD. GSEA revealed that low expression of SFTPD was positively correlated with the pathways associated with drug resistance, such as DNA replication, cell cycle, drug metabolism, and DNA damage repair, including mismatch repair (MMR), base excision repair (BER), homologous recombination (HR), and nucleotide excision repair (NER). The SFTPD expression was negatively correlated with the drug sensitivity of alectinib according to RNAactDrug database. The expression of SFTPD was further validated in parental H3122 cells and alectinib-resistant H3122 cells by quantitative reverse transcription PCR (RT-qPCR). In conclusion, our study found that the five hub genes, especially low expression of SFTPD, are closely related to alectinib resistance in patients with LUAD.

Comprehensive analysis of ZNF692 as a potential biomarker associated with immune infiltration in a pan cancer analysis and validation in hepatocellular carcinoma.

Currently, the roles of ZNF692 have been documented exclusively in lung, colon, and cervical cancers. However, its involvement in pan cancer remains unknown. In this study, we employed bioinformatics analysis and experimental validation to investigate the role of ZNF692 in pan cancer. Our findings revealed aberrant expression of ZNF692 across various types of cancer. High expression of ZNF692 was associated with poor overall survival (OS) in ACC, COAD, KIRC, LAML, and LIHC. ZNF692 exhibited promising diagnostic potential in certain tumor types. A significant correlation was observed between high ZNF692 expression and advanced stages of ACC, BLCA, KICH, KIRC, LIHC, and OV. The expression of ZNF692 exhibited a significant association with microsatellite instability (MSI) in eight types of cancer and tumor mutational burden (TMB) in ten types of cancer. A noteworthy correlation was observed between ZNF692 expression and immune infiltration as well as immune checkpoints. Amplification of ZNF692 emerged as the most frequent alteration in pan cancer. ZNF692 was implicated in various biological processes, cellular components, and molecular functions within the context of pan cancer. It is plausible that ZNF692 may contribute to chemotherapy and potentially be linked to chemoresistance. We constructed a competing endogenous RNA (ceRNA) network involving AC009403.11/miR-126-3p/ZNF692 in hepatocellular carcinoma (HCC). The expression of ZNF692 exhibited a notable upregulation in HCC cell lines. Aberrant expression of ZNF692 was observed across various types of cancer. ZNF692 holds potential as a valuable diagnostic, prognostic, and therapeutic target in the context of pan cancer.