Characteristics of patients with schizophrenia switching from oral antipsychotics to once-monthly paliperidone palmitate (PP1M): a systematic review.

BACKGROUND: The utilization of once-monthly paliperidone palmitate (PP1M) in schizophrenia treatment has increased due to its enhanced adherence and convenience. However, there is limited evidence on patient characteristics that may influence treatment outcomes when switching from oral antipsychotics (OAPs) to PP1M therapy. This systematic review aims to identify such patient characteristics and explore potential beneficial factors to aid healthcare professionals in clinical practice. METHODS: A systematic literature search was conducted in the PubMed, Embase, and Cochrane Library databases up to July 19, 2022. Studies related to patients with schizophrenia who had been previously treated with OAPs and switched to PP1M were identified and included. Outcomes included the Positive and Negative Syndrome Scale (PANSS) total score, the clinical Global Impressions - Severity (CGI-S) score, the Personal and Social Performance (PSP) total score, and hospitalisation rate. Data were independently extracted and analysed. The results were presented through a narrative synthesis. RESULTS: Eleven studies with a total of 4150 patients were included, identifying nine potential characteristics. The most commonly reported characteristics was patient's prior treatment with OAPs, followed by the stage of disease, duration of illness (DI), ethnicity, reason for switching to PP1M, history of hospitalisation, time of start injection of PP1M, the PANSS and PSP total score at baseline. Patients in the acute stage, with a shorter DI, a less than 1-week time interval to PP1M injection, and a lower PANSS total score at baseline may have a trend on providing better improvements on PANSS total score. Acute stage and shorter DI also showed potential trends in reducing CGI-S score. Early initiation of PP1M, switching for reasons other than lack of efficacy, and a higher PSP score at baseline exhibited potential trends towards better PSP total score improvements. CONCLUSION: Our findings may suggest that patients in acute stage, with a shorter duration of illness, with early initiation of PP1M injection, and lower PANSS or PSP scores may trend towards better clinical results when transitioning to PP1M from OAPs. Further research is necessary to validate these potential associations and identify any unexplored characteristics. Such investigations are crucial for providing comprehensive clinical recommendations and informing treatment strategies in this context.

Factors affecting the reproductive outcome in reciprocal translocation carriers undergoing preimplantation genetic testing for structural rearrangements (PGTSR).

OBJECTIVE: To investigate the reproductive outcomes of balanced reciprocal translocation carriers and evaluate the association between the number of metaphase-II oocytes retrieved and cumulative live birth rates (LBRs). METHODS: This retrospective analysis included 344 preimplantation genetic testing (PGT) for structural rearrangement cycles of 281 couples with balanced reciprocal translocations between January 2018 and January 2021. All patients included in the analysis had either delivered a baby or had used all their embryos after one stimulation cycle. All women were followed up for at least 2 years. RESULTS: After ovarian stimulation and oocyte fertilization, 44.2% of PGT for structural rearrangements cycles achieved a live birth. Carrier's sex and female age did not affect the cumulative LBR of reciprocal translocation carriers. Cumulative LBRs steadily increased with the number of oocytes, reaching 64% when >20 oocytes were retrieved. The cutoff values for achieving at least one live birth were 9.5 metaphase-II (MII) oocytes and 3.5 biopsied embryos. CONCLUSION: Couples with reciprocal translocations have lower transferable embryo rates and cumulative LBRs. The MII oocytes retrieved may be a crucial factor for cumulative LBRs. A high ovarian response may further increase cumulative LBRs, but avoidance of ovarian hyperstimulation syndrome or other iatrogenic complications should be considered.

Factors Associated with Symptom Stabilization that Allow for Successful Transition from Once-Monthly Paliperidone Palmitate to Three-Monthly Paliperidone Palmitate: A Post Hoc Analysis Examined Clinical Characteristics in Chinese Patients with Schizophrenia.

BACKGROUND AND OBJECTIVES: Identifying key factors for a successful transition from once-monthly paliperidone palmitate (PP1M) to three-monthly paliperidone palmitate (PP3M) is crucial for improving treatment outcomes, enhancing patient adherence, and reducing relapse risk in patients with schizophrenia. Providing region-specific insights for evidence-based clinical decisions can aid clinicians in optimizing transition strategies for Chinese patients with schizophrenia. Therefore, the objective of this post hoc analysis of a double-blind parallel-group multicenter phase 3 study (NCT01515423) was to identify factors related to the disease stabilization that may allow for a successful transition from PP1M to PP3M in the treatment of Chinese patients with schizophrenia. METHODS: Adults (18-70 years) diagnosed with schizophrenia using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition text revision, for over 1 year and with a baseline Positive and Negative Syndrome Scale (PANSS) total score between 70 and 120 were entered into an open-label (OL) phase receiving PP1M for 17 weeks. After the 17-week OL phase, patients who met the criteria necessary for stabilization were randomized (1:1) to PP1M (fixed-dose, 50, 75, 100, or 150 mg eq.) or PP3M (fixed-dose, 175, 263, 350, or 525 mg eq.) in a 48-week double-blind phase. Stabilization was defined as a PANSS total score < 70, PANSS item (P1, P2, P3, P6, P7, G8, G14) scores ≤ 4, and a reduction in Clinical Global Impression Severity (CGI-S) score of ≥ 1 from OL baseline. This post hoc analysis evaluated changes and trends in symptom severity using PANSS, changes in mental states using CGI-S, and changes in personal and social functioning using Personal and Social Performance (PSP) scores from baseline to the endpoint of the OL phase in patients who either met or did not meet the stabilization criteria (stabilized versus non-stabilized group). Comparison of changes and trends in the clinical scores between the stabilized group and non-stabilized group were conducted using linear mixed model and Mann-Kendall trend analysis, respectively. Univariate and multivariate logistic regression analyses were conducted to explore factors associated with stabilization status for transition. RESULTS: Of 296 patients enrolled, 210 achieved disease stabilization (106 patients and 104 patients were randomized to PP1M and PP3M, respectively). Significant downward trends in the PANSS and CGI-S scores were detected in the stabilized patients (n = 210, ZPANSS = -2.21, p = 0.028; ZCGI-S = -2.21, p = 0.028) but not in the non-stabilized patients (n = 86). No significant trends in the PSP scores were observed in either group. The factors significantly associated with disease stabilization were the CGI-S score at baseline [odds ratio (OR) = 0.22, 95% confidence interval (CI): 0.09, 0.5), reduction of the PANSS score at week 13 (OR = 1.11, 95% CI: 1.06, 1.17), and reduction of CGI-S score at week 13 (OR = 2.27, 95% CI: 1.03, 5.02). CONCLUSION: A lower CGI-S total score at baseline and greater reductions in PANSS and CGI-S scores at week 13 were associated with patients achieving disease stabilization, that may allow for a successful transition. Evidence from this study indicates that better disease condition at baseline, early functional improvement and symptomatic relief were the key factors associated with disease stabilization. The findings may guide clinicians to identify suitable patients for transition from PP1M to PP3M and further optimize the use of PP3M in China. CLINICAL TRIALS REGISTRATION: EudraCT number: 2011-004889-15 and ClinicalTrials.gov (identifier: NCT01515423) for the original double-blind randomized study.

Impact of neoadjuvant chemotherapy on breast cancer-related lymphedema after axillary lymph node dissection: a retrospective cohort study.

PURPOSE: We aimed to evaluate whether neoadjuvant chemotherapy (NAC) could be a risk factor for breast cancer-related lymphedema (BCRL) associated with axillary lymph node dissection (ALND). PATIENTS AND METHODS: A total of 596 patients with cT0-4N0-3M0 breast cancer who underwent ALND and chemotherapy were retrospectively analyzed between March 2012 and March 2022. NAC was administered in 188 patients (31.5%), while up-front surgery in 408 (68.5%). Univariate and multivariable Cox regression analyses were performed to determine whether NAC was an independent risk factor for BCRL. With propensity score matching (PSM), the NAC group and up-front surgery group were matched 1:1 by age, body mass index (BMI), molecular subtypes, type of breast surgery, and the number of positive lymph nodes. Kaplan-Meier survival analyses were performed for BCRL between groups before and after PSM. Subgroup analyses were conducted to explore whether NAC differed for BCRL occurrence in people with different characteristics. RESULTS: At a median follow-up of 36.3 months, 130 patients (21.8%) experienced BCRL [NAC, 50/188 (26.60%) vs. up-front surgery, 80/408 (19.61%); P = 0.030]. Multivariable analysis identified that NAC [hazard ratio, 1.503; 95% CI (1.03, 2.19); P = 0.033] was an independent risk factor for BCRL. In addition, the hormone receptor-negative/human epidermal growth factor receptor 2-negative (HR-/HER2-) subtype, breast-conserving surgery (BCS), and increased positive lymph nodes significantly increased BCRL risk. After PSM, NAC remained a risk factor for BCRL [hazard ratio, 1.896; 95% CI (1.18, 3.04); P = 0.007]. Subgroup analyses showed that NAC had a consistent BCRL risk in most clinical subgroups. CONCLUSION: NAC receipt has a statistically significant increase in BCRL risk in patients with ALND. These patients should be closely monitored and may benefit from early BCRL intervention.

CCK2-receptor deficiency impairs immune balance by influencing CD4+ T cells development by inhibiting cortical-thymic-epithelial-cells.

Immune balance is crucial for an organism's survival and is inseparable from the regulation of the nervous system. Accumulating evidence indicates that cholecystokinin (CCK) plays an important role in mediating the immune response through the activation of cholecystokinin receptors (CCKRs). However, it remains unclear whether CCKRs deficiency may impair immune balance. Here, we showed that CCK2R-deficient adult mice were immunocompromised and had an increased risk of shock and even death in an endotoxemia (ETM)/endotoxin shock (ES) model. In addition, in both adult and juvenile mice, CCK2R deficiency not only influenced the development of CD4 single-positive (SP) thymocytes in thymic positive selection but also decreased the population of CD3+ CD4+ T cells in the spleen. More importantly, CCK2R deficiency inhibited the expression of major histocompatibility complex class II (MHC II) and CD83 on cortical thymic epithelial cells (cTECs) in juvenile and adult mice. Overall, our study suggests that CCK2R is essential for maintaining CD4+ T cell development in the thymus and reveals that CCK2R plays an important role in maintaining immune balance.

Characteristics of Two mcr-1-Harboring IncHI2 Plasmids from Clinical Salmonella Isolates in Jiaxing City.

Salmonella is a primary cause of foodborne diseases, and the increasing prevalence of mcr-1-carrying plasmids, which confer colistin resistance to Salmonella, poses significant global health concerns. As the frequency of occurrence of the mcr-1 gene is increasing globally, we studied the prevalence of mcr-1 in clinical Salmonella isolates by analyzing 195 clinical strains isolated in 2020. Of the 195 Salmonella isolates, 41 isolates were resistant to colistin. We found mcr-1 in two strains (Salmonella Typhimurium ZJJX20006 and Salmonella Kentucky ZJJX20014), which we analyzed in detail via whole-genome sequencing and antibiotic susceptibility testing. Two strains displayed resistance to ampicillin, ampicillin-sulbactam, tetracycline, chloramphenicol, and cotrimoxazole, while ZJJX20006 displayed resistance to colistin and ZJJX20014 was sensitive. Genomic analysis revealed that these strains had plasmid-encoded mcr-1 in IncHI2 plasmids, which were not similar to the mcr-1-IncX4 identified in 2016. These two strains also harbored other drug resistance genes, including blaOXA-1 and blaCTX-M-14. Our findings may help clarify the molecular mechanisms of mcr-1 dissemination among Salmonella strains in Jiaxing City and offer insights into the evolution of mcr-1 in Salmonella.

Ceruloplasmin is associated with the infiltration of immune cells and acts as a prognostic biomarker in patients suffering from glioma.

Glioma is regarded as a prevalent form of cancer that affects the Central Nervous System (CNS), with an aggressive growth pattern and a low clinical cure rate. Despite the advancement of the treatment strategy of surgical resection, chemoradiotherapy and immunotherapy in the last decade, the clinical outcome is still grim, which is ascribed to the low immunogenicity and tumor microenvironment (TME) of glioma. The multifunctional molecule, called ceruloplasmin (CP) is involved in iron metabolism. Its expression pattern, prognostic significance, and association with the immune cells in gliomas have not been thoroughly investigated. Studies using a variety of databases, including Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and Gliovis, showed that the mRNA and protein expression levels of CP in patients suffering from glioma increased significantly with an increasing glioma grade. Kaplan-Meier (KM) curves and statistical tests highlighted a significant reduction in survival time of patients with elevated CP expression levels. According to Cox regression analysis, CP can be utilized as a stand-alone predictive biomarker in patients suffering from glioma. A significant association between CP expression and numerous immune-related pathways was found after analyzing the data using the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Tumor Immune Estimation Resource (TIMER) and CIBERSORT analyses indicated a substantial correlation between the CP expression and infiltration of immunocytes in the TME. Additionally, immune checkpoints and CP expression in gliomas showed a favorable correlation. According to these results, patients with glioma have better prognoses and levels of tumor immune cell infiltration when their CP expression is low. As a result, CP could be used as a probable therapeutic target for gliomas and potentially anticipate the effectiveness of immunotherapy.

Hierarchical transcriptional network governing heterogeneous T cell exhaustion and its implications for immune checkpoint blockade.

The fundamental principle of immune checkpoint blockade (ICB) is to protect tumor-infiltrating T cells from being exhausted. Despite the remarkable success achieved by ICB treatment, only a small group of patients benefit from it. Characterized by a hypofunctional state with the expression of multiple inhibitory receptors, exhausted T (Tex) cells are a major obstacle in improving ICB. T cell exhaustion is a progressive process which adapts to persistent antigen stimulation in chronic infections and cancers. In this review, we elucidate the heterogeneity of Tex cells and offer new insights into the hierarchical transcriptional regulation of T cell exhaustion. Factors and signaling pathways that induce and promote exhaustion are also summarized. Moreover, we review the epigenetic and metabolic alterations of Tex cells and discuss how PD-1 signaling affects the balance between T cell activation and exhaustion, aiming to provide more therapeutic targets for applications of combinational immunotherapies.

Effectiveness and Safety of Switching from Oral Antipsychotics to Once-Monthly Paliperidone Palmitate (PP1M) in the Management of Schizophrenia: A Systematic Review and Meta-Analysis.

BACKGROUND: Considering the improvement in adherence and convenience, once-monthly paliperidone palmitate (PP1M) has been increasingly used in the treatment of schizophrenia. However, the outcomes for patients who switch from oral antipsychotics (OAPs) to PP1M have not been reliably assessed. The objective of this systematic review and meta-analysis was to investigate the efficacy and safety of PP1M in the management of patients with schizophrenia with a prior history of OAP use. METHODS: We conducted a systematic search in PubMed, EMBASE, and the Cochrane Library on 19 July 2022 to identify eligible studies. All studies that examined the effectiveness and safety of switching from OAPs to PP1M in patients with schizophrenia were included. The primary outcomes were relapse rate, hospitalisation rate, and the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score. The secondary outcomes included the changed number of inpatient visits, changed length of stay hospitalisation, change from baseline in the Clinical Global Impressions-Severity (CGI-S) score and the personal and social performance (PSP) total score, response rate, proportion of treatment discontinuation, and adverse events. We included randomised-controlled trials (RCTs), single-arm studies, and observational studies. Case reports, case series, and reviews were excluded. The quality assessment of included studies was performed using the Revised Cochrane risk-of-bias tool for randomised trials (RoB2), the 9-point Newcastle-Ottawa Scale (NOS) instrument for non-randomised studies and cohort studies, and the 12-item National Institutes of Health (NIH) quality assessment tool for before-after (Pre-Post) study without control group. Follow-up times were reported as short- (≤ 13 weeks), medium- (14-26 weeks), and long term (≥ 27 weeks). Data were pooled using meta-analysis. RESULTS: Fifteen studies with a total of 4740 patients were included. The long-term relapse rates and hospitalisation rates were 12% (95% CI 0.07-0.18) and 18% (95% CI 0.15-0.20), respectively. The short-, medium-, and long-term change in PANSS total score was - 21.69 (95% CI - 30.02 to -13.36), - 14.98 (95% CI - 21.45 to - 8.51) and - 17.88 (95% CI - 31.94 to -3.82), respectively. Approximately 50% of patients reported at least a 30% reduction in the PANSS score at the short-term follow-up. Improvements in CGI-S and PSP score were observed during various periods. There was a reduction in the length of stay hospitalisation and the number of inpatient visits at the medium- and long-term follow-ups. Low discontinuation and adverse event rates were reported. CONCLUSION: Based on our findings, this study may support the efficacy and safety of switching from OAPs to PP1M for the treatment of patients with schizophrenia. Future large-scale studies are warranted to confirm our findings.

PSMD4 drives progression of hepatocellular carcinoma via Akt/COX2 pathway and p53 inhibition.

The ubiquitin-dependent proteolytic pathway is crucial for cellular regulation, including control of the cell cycle, differentiation, and apoptosis. Proteasome 26S Subunit Ubiquitin Receptor, Non-ATPase 4, (PSMD4) is a member of the ubiquitin proteasome family that is upregulated in multiple solid tumors, including hepatocellular carcinoma (HCC), and the existence of PSMD4 is associated with unfavorable prognosis. In this study, transcriptome sequencing of HCC tissues and non-tumor hepatic tissues from the public database Cancer Genome Atlas (TGCA) revealed a high expression of PSMD4. Additionally, PSMD4 loss in HCC cells suppressed the tumor development in mouse xenograft model. PSMD4, which is maintained by inflammatory factors secreted from tumor matrix cells, positively mediates cell growth and is associated with Akt/GSK-3ß/ cyclooxygenase2 (COX2) pathway activation, inhibition of p53 promoter activity, and increased p53 degradation. However, the domain without the C-terminus (VWA+UIM1/2) sustained the activation of p53 transcription. Thus, our findings suggest that PSMD4 is involved in HCC tumor growth through COX2 expression and p53 downregulation. Therapeutic strategies targeting PSMD4 and its downstream effectors could be used for the treatment of PSMD4-abundant HCC patients.

Specific mating behavior of Malayan pangolin (Manis javanica) in captivity.

Pangolin is a mysterious animal in the Family Pholidota, Mammalia. Malayan pangolin (Manis javanica) is one of eight existing species and is listed in Manis. With the number of wild pangolins (Manis spp.) rapidly decreasing, captive breeding has become an important way to protect them from extinction. The research on mating behavior of pangolins is an important content to understand its reproductive characteristics and develop breeding management. From 2016 to 2022, a total of 360 mating events were observed in six males and 24 females through closed circuit television (CCTV) surveillance. The results show that males do not engage in complex courtship behavior before mating. In addition, we found that male pangolins adopted a ventrolateral mating position. Once males selected the side (left/right) of the female pangolin from which to approach to mate, they usually remained on the same side for subsequent mating, suggesting that male pangolins may have a preference in mating position. Finally, all mating events were observed at 1.72 ± 1.47 (n = 83, Mean ± SD) days after cohabitation and adjustment time before mating (from the male touching the female to intromission) took 4.98 ± 3.86 mins (n = 323). During mating, males hugged females and remained still for 47.37 ± 10.08 seconds (n = 323), which is the ejaculation and post-ejaculation quiescent time. Remarkably, we observed for the first time two peak mating times, 19:00 to 22:00 and 1:00 to 3:00, suggesting that they may have a preference for mating times. This study provides new insight into the mating behavior of M. javanica and contributes to the development of scientific conservation measures to improve the reproductive capacity of M. javanica.

Retrospective Analysis of Meiotic Segregation Pattern and Reproductive Outcomes in Blastocysts from Robertsonian Preimplantation Genetic Testing Cycles.

In this retrospective study, 120 heterozygous Robertsonian translocation carriers undergoing preimplantation genetic testing (PGT) were included, between January 2018 and September 2021. Meiotic segregation patterns of 462 embryos from 51 female carriers and 69 male carriers were analyzed according to chromosome type, carrier's sex, and female age. The proportion of alternate embryos in female carriers was slightly lower than that in male carriers [P < 0.001, odds ratio (OR) = 0.512]. By contrast, no difference was observed among Rob (13;14), Rob (14;21), and rare RobT groups. Stratification analysis of female carriers' age doses showed no significant increase in unbalanced chromosomal abnormalities. Reproductive outcomes of 144 frozen-thawed cycles were analyzed. All 144 blastocysts were transferred, and there were no significant differences in the clinical pregnancy rates per transfer (CPR), miscarriage rates (MR), live birth rates per transfer (LBR), and cumulative live birth rates between female carriers and male carriers. In addition, couples in Rob (13;14), Rob (14;21), and rare RobTs groups had comparative clinical pregnancy rates per transfer (CPR), miscarriage rates (MR), live birth rates per transfer (LBR), and cumulative live birth rates. Our study demonstrated that the meiotic segregation pattern of Robertsonian translocations carriers is associated with the carrier's sex, but not the carrier's translocation type and female age. In addition, the sex of translocation carriers only affects the meiotic segregation pattern but does not influence the subsequent viability of normal embryos and live birth.

Synchronous multiple primary malignant neoplasms in breast, kidney, and bilateral thyroid: A case report.

BACKGROUND: Multiple primary malignant neoplasms (MPMNs) are rare, while synchronous MPMNs (SMPMNs) are even less common. Owing to the progression of medical technology and the extension of life expectancy, its incidence is gradually increasing. CASE SUMMARY: Although reports of breast and thyroid dual cancers are common, cases of an additional diagnosis of kidney primary cancer within the same individual are rare. CONCLUSION: We present a case of simultaneous MPMN of three endocrine organs, reviewing the relevant literature to enhance our understanding of SMPMNs while emphasizing the increasingly important need for accurate diagnosis and multidisciplinary management whenever this challenging situation arises.

Higher chromosomal abnormality rate in blastocysts from a subset of patients with pericentric inversion (Inv) 1 variant.

The purpose of this study was to evaluate the incidence of unbalanced chromosome rearrangement in blastocyst-stage embryos from carriers of pericentric inversion of chromosome 1 (PEI-1). A total of 98 embryos from 22 PEI-1 carriers were tested for unbalanced rearrangements, originating from inversion carriers, and overall aneuploidy. Logistic regression analysis indicated that the ratio of inverted segment size to chromosome length was a statistically significant risk factor for unbalanced chromosome rearrangement from PEI-1 carriers (p = 0.003). The optimal cut-off values to predict the risk of unbalanced chromosome rearrangement was 36%, with the incidence being 2.0% in the <36% group and 32.7% in the ≥36% group. The unbalanced embryo rate was 24.4% in male carriers compared to 12.3% in female carriers. Inter-chromosomal effect analysis was performed using 98 blastocysts from PEI-1 carriers and 116 blastocysts from age-matched controls. PEI-1 carriers had similar sporadic aneuploidy rates compared to those of age-matched controls at 32.7 vs. 31.9%, respectively. In conclusion, the risk of unbalanced chromosome rearrangement is affected by inverted segment size in PEI-1 carriers.

High-Quality Genomes of Pangolins: Insights into the Molecular Basis of Scale Formation and Adaption to Myrmecophagous Diet.

Pangolins are one of nature's most fascinating species being scales covered and myrmecophagous diet, yet relatively little is known about the molecular basis. Here, we combine the multi-omics, evolution, and fundamental proteins feature analysis of both Chinese and Malayan pangolins, highlighting the molecular mechanism of both myrmecophagous diet and scale formation, representing a fascinating evolutionary strategy to occupy the unique ecological niches. In contrast to conserved organization of epidermal differentiation complex, pangolin has undergone large scale variation and gene loss events causing expression pattern and function conversion that contribute to cornified epithelium structures on stomach to adapt myrmecophagous diet. Our assemblies also enable us to discover large copies number of high glycine-tyrosine keratin-associated proteins (HGT-KRTAPs). In addition, highly homogenized tandem array, amino content, and the specific expression pattern further validate the strong connection between the molecular mechanism of scale hardness and HGT-KRTAPs.

Endoplasmic reticulum stress mediates nickel chloride-induced epithelial­mesenchymal transition and migration of human lung cancer A549 cells through Smad2/3 and p38 MAPK activation.

BACKGROUND: The endoplasmic reticulum (ER) is a cellular membrane-bound organelle whereby proteins are synthesized, folded and glycosylated. Due to intrinsic (e.g., genetic) and extrinsic (e.g., environmental stressors) perturbations, ER proteostasis can be deregulated within cells which triggers unfolded protein response (UPR) as an adaptive stress response that may impact the migration and invasion properties of cancer cells. However, the mechanisms underlying the nickel compounds on lung cancer cell migration and invasion remain uncertain. OBJECTIVE: We aimed to study whether Nickel chloride (NiCl2) induces ER stress in lung cancer cells, and whether ER stress is involved in modulating epithelial-mesenchymal transition (EMT) and migration by Smads and MAPKs pathways activation following NiCl2 treatment. METHODS: A549 cells were treated with NiCl2 to determine the cell viability using MTT assay. The wound healing assay was used to evaluate cell migration ability. ER ultrastructure was observed by transmission electron microscopy. Western blotting assay was performed to evaluate the protein levels of BIP, PERK, IRE-1α, XBP-1 s, and ATF6 for ER stress and UPR, E-cadherin and Vimentin for EMT, p-Smad2/3, p-ERK, p-JNK, and p-P38 for activation of Smads and MAPKs signaling pathways. RESULTS: The expression levels of BIP, PERK, IRE-1α, XBP-1 s, and ATF6 were significantly increased following treatment with NiCl2 in time- and dose-effect relationship. The ER stress inhibitor 4-PBA downregulated the expression levels of the above five proteins, and reversed the decrease in E-cadherin protein level and the increase in vimentin protein expression and cell migration abilities caused by NiCl2. Furthermore, 4-PBA significantly reduced nickel chloride-induced Smad2/3 and p38 MAPK pathway activation, while not affected ERK and JNK MAPK pathways. CONCLUSION: NiCl2 triggers ER stress and UPR in A549 cells. Moreover, 4-PBA alleviates NiCl2-induced EMT and migration ability of A549 cells possibly through the Smad2/3 and p38 MAPK pathways activation, rather than ERK and JNK MAPK pathways.

Rational Design of Inhibitor-Encapsulated Bio-MOF-1 for Dual Corrosion Protection.

Searching for the efficient and sustainable inhibitors to defend metal corrosion in the marine environment has received a great deal attention in both academia and industry. In this work, a new strategy was developed to encapsulate benzimidazole (BI) inhibitor guest molecules into the micropores of bio-MOF-1, which was constructed with the other natural adenine inhibitor. Electrochemical characterizations revealed that the slowly sustained release of BI and adenine inhibitors from the BI@bio-MOF-1 composite presented excellent anti-corrosion durability in the whole mild steel corrosion process. The impedance arc value attained approximately 5000 Ω·cm2 at initially 2 h and further increased to 6000 Ω·cm2 after 5 days immersion in 0.5 M NaCl solution, and the inhibition efficiency reached 85.36% due to the synergistic dual inhibitive effect of BI@bio-MOF-1 composite. The dual inhibition-based bio-MOF-1 composite equipped strong metal-chelating capability and response durability, exhibiting high potentiality for metal anti-corrosion applications.

Weaning period and growth patterns of captive Sunda pangolin (Manis javanica) cubs.

This study tracked and recorded the weight changes of 13 captive Sunda pangolin cubs from lactation to maturity to explored the appropriate weaning time and reveal the rules of its weight growth. SPSS 25.0 was used to build a cubic equation model to fit the body weight change rules of 4 individuals who nonvoluntarily ingested artificial feed (NIAF) at 127 days after birth and 5 individuals who voluntarily ingested artificial feed (VIAF) at 86-108 days after birth. The body weight of NIAF cubs aged 0-120 days and VIAF cubs aged 0-150 days were estimated according to the fitting model. An independent sample T-test was performed on the mean body weight of the two groups during the late lactation period. The results showed that at 105 days after birth, the body weight of the VIAF group was significantly higher than that of the NIAF group (P = 0.049), and the body weight of the VIAF group was extremely significantly higher than that of the NIAF group at 114 days (P = 0.008); The peak cumulative body weight of the NIAF cubs during lactation appeared around 130 days of age (n = 3); The mortality rate was 66.7% (n = 3) after about 150 days if the feed was continuously consumed nonvoluntarily. It was concluded that the milk secretion period of the mother is about 0-5 months after giving birth; the weaning period of the cubs should be 4-5 months after birth. If the cubs don't follow the mother to eat artificial feed for 3 months after birth, it can start be induced with artificial diet which adds termites, and the time point cannot be later than 130 days, otherwise it is not conducive to the survival of the cubs; When sexually mature, the body length and body weight of female cubs account for about 84% and 60% of the adult, respectively; the body maturity and body weight of female cubs tend to be stable about 15.3 months and 16.4 months, respectively. Finally, a special needle-shaped nipples and nursing patterns of female Sunda pangolins were also recorded in this study. These findings play an important role in guiding the nursing of captive Sunda pangolin cubs and other pangolin cubs. It is expected to improve the survival rate of the cubs by exploring the appropriate weaning time and the rules of weight growth. By scientifically planning the reproductive cycle of the female Sunda pangolins, our goal is to expand the population size and eventually release to the wild, meanwhile improving knowledge of this critically endangered species.

Lipocalin-2 inhibits pancreatic cancer stemness via the AKT/c-Jun pathway.

Cancer stem cells (CSCs) are involved in cancer recurrence and metastasis owing to their self-renewal properties and drug-resistance capacity. Lipocalin-2 (Lcn2) of the lipocalin superfamily is highly expressed in pancreatic cancer. Nevertheless, reports on the involvement of Lcn2 in the regulation of pancreatic CSC properties are scant. This study is purposed to investigate whether Lcn2 plays a crucial role in CSC renewal and stemness maintenance in pancreatic carcinoma. Immunohistochemistry results of tumor tissue chips together with Gene Expression Omnibus sequencing files confirmed that Lcn2 is highly expressed in pancreatic carcinoma compared with that in normal tissues. The exogenous expression of Lcn2 attenuated CSC-associated SOX2, CD44, and EpCAM expression and suppressed sarcosphere formation and tumorigenesis in the pancreatic carcinoma cell line PANC-1, which showed low expression of Lcn2. However, Lcn2 knockout in BxPC-3 cell line, which presented high Lcn2 expression, promoted CSC stemness, further enhancing sarcosphere formation and tumorigenesis. Moreover, Lcn2 was found to regulate stemness in pancreatic cancer depending on the activation of AKT and c-Jun. Lcn2 suppresses stemness properties in pancreatic carcinoma by activating the AKT-c-Jun pathway, and thus, it may be a novel candidate to suppress the stemness of pancreatic cancer. This study provides a new insight into disease progression.