Proteomic profiling of TBC1 domain family member 21-null sperms reveals the critical roles of TEKT 1 in their tail defects.

BACKGROUND: Approximately 7% of the males exhibit reduced fertility; however, the regulatory genes and pathways involved remain largely unknown. TBC1 domain family member 21 (TBC1D21) contains a conserved RabGAP catalytic domain that induces GDP/GTP exchange to inactivate Rabs by interacting with microtubules. We previously reported that Tbc1d21-null mice exhibit severe sperm tail defects with a disrupted axoneme, and that TBC1D21 interacts with RAB10. However, the pathological mechanisms underlying the Tbc1d21 loss-induced sperm tail defects remain unknown. RESULTS: Murine sperm from wild-type and Tbc1d21-null mice were comparatively analyzed using proteomic assays. Over 1600 proteins were identified, of which 15 were significantly up-regulated in Tbc1d21-null sperm. Notably, several tektin (TEKT) family proteins, belonging to a type of intermediate filament critical for stabilizing the microtubular structure of cilia and flagella, were significantly up-regulated in Tbc1d21-/- sperm. We also found that TBC1D21 interacts with TEKT1. In addition, TEKT1 co-localized with RAB10 during sperm tail formation. Finally, we found Tbc1d21-null sperm exhibited abnormal accumulation of TEKT1 in the midpiece region, accompanied by disrupted axonemal structures. CONCLUSIONS: These results reveal that TBC1D21 modulates TEKTs protein localization in the axonemal transport system during sperm tail formation.

Deleterious genetic changes in AGTPBP1 result in teratozoospermia with sperm head and flagella defects.

Approximately 10%-15% of couples worldwide are infertile, and male factors account for approximately half of these cases. Teratozoospermia is a major cause of male infertility. Although various mutations have been identified in teratozoospermia, these can vary among ethnic groups. In this study, we performed whole-exome sequencing to identify genetic changes potentially causative of teratozoospermia. Out of seven genes identified, one, ATP/GTP Binding Protein 1 (AGTPBP1), was characterized, and three missense changes were identified in two patients (Affected A: p.Glu423Asp and p.Pro631Leu; Affected B: p.Arg811His). In those two cases, severe sperm head and tail defects were observed. Moreover, AGTPBP1 localization showed a fragmented pattern compared to control participants, with specific localization in the neck and annulus regions. Using murine models, we found that AGTPBP1 is localized in the manchette structure, which is essential for sperm structure formation. Additionally, in Agtpbp1-null mice, we observed sperm head and tail defects similar to those in sperm from AGTPBP1-mutated cases, along with abnormal polyglutamylation tubulin and decreasing △-2 tubulin levels. In this study, we established a link between genetic changes in AGTPBP1 and human teratozoospermia for the first time and identified the role of AGTPBP1 in deglutamination, which is crucial for sperm formation.

Stimuli-Responsive Polymersomes: Reshaping the Immunosuppressive Tumor Microenvironment.

The progression of cancer involves mutations in normal cells, leading to uncontrolled division and tissue destruction, highlighting the complexity of tumor microenvironments (TMEs). Immunotherapy has emerged as a transformative approach, yet the balance between efficacy and safety remains a challenge. Nanoparticles such as polymersomes offer the possibility to precisely target tumors, deliver drugs in a controlled way, effectively modulate the antitumor immunity, and notably reduce side effects. Herein, stimuli-responsive polymersomes, with capabilities for carrying multiple therapeutics, are highlighted for their potential in enhancing antitumor immunity through mechanisms like inducing immunogenic cell death and activating STING (stimulator of interferon genes), etc. The recent progress of utilizing stimuli-responsive polymersomes to reshape the TME is reviewed here. The advantages and limitations to applied stimuli-responsive polymersomes are outlined. Additionally, challenges and future prospects in leveraging polymersomes for cancer therapy are discussed, emphasizing the need for future research and clinical translation.

Comparative analysis of visual-thermal perceptions and emotional responses in outdoor open spaces: Impacts of look-up vs. look-forward viewing perspectives.

Horizontal and vertical viewing perspectives exert varying influences on the environmental perceptions and emotional states of college students. Despite this, scant research addresses the impact on this demographic. We selected typical campus open spaces for comprehensive physical parameter assessments, encompassing meteorological and spatial characteristics. A cohort of 36 healthy college students participated in a questionnaire survey designed to ascertain shifts in visual comfort, thermal comfort, and emotional responses when viewing landscapes in look-forward and look-up orientations. Key findings following both viewing modalities included: 1) a notable rise in mean visual comfort vote (MVCV), by 1.22 for look-forward and 1.01 for look-up, with a pronouncedly higher sunlight sensation vote (SSV) for the latter orientation; 2) a significant increase in thermal comfort vote (TCV), although the difference in increments between the two viewing angles was minimal; 3) Positive affect (PA) exhibited considerable improvement in both viewing conditions, while negative affect (NA) was markedly reduced in the look-up condition relative to look-forward viewing; 4) The SSV was predominantly influenced by the trunk ratio and canopy-to-trunk ratio, with substantial weights of 31.47% and 32.15%, respectively. Landscape element diversity emerged as the most critical factor affecting visual comfort vote (VCV) and aesthetic assessment score (AAS), with overwhelming weights of 70.67% and 63.15%, respectively. Moreover, the leaf ratio was identified as the chief determinant of emotional responses. Our results provide insights into the design of campus spaces for enhanced student well-being.

Insights into ZmWAKL in maize kernel development: genome-wide investigation and GA-mediated transcription.

BACKGROUND: The functional roles of the Wall Associated Kinase (WAK) and Wall Associated Kinase Like (WAKL) families in cellular expansion and developmental processes have been well-established. However, the molecular regulation of these kinases in maize development is limited due to the absence of comprehensive genome-wide studies. RESULTS: Through an in-depth analysis, we identified 58 maize WAKL genes, and classified them into three distinct phylogenetic clusters. Moreover, structural prediction analysis showed functional conservation among WAKLs across maize. Promoter analysis uncovered the existence of cis-acting elements associated with the transcriptional regulation of ZmWAKL genes by Gibberellic acid (GA). To further elucidate the role of WAKL genes in maize kernels, we focused on three highly expressed genes, viz ZmWAKL38, ZmWAKL42 and ZmWAKL52. Co-expression analyses revealed that their expression patterns exhibited a remarkable correlation with GA-responsive transcription factors (TF) TF5, TF6, and TF8, which displayed preferential expression in kernels. RT-qPCR analysis validated the upregulation of ZmWAKL38, ZmWAKL42, ZmWAKL52, TF5, TF6, and TF8 following GA treatment. Additionally, ZmWAKL52 showed significant increase of transcription in the present of TF8, with ZmWAKL52 localizing in both the plasma membrane and cell wall. TF5 positively regulated ZmWAKL38, while TF6 positively regulated ZmWAKL42. CONCLUSIONS: Collectively, these findings provide novel insights into the characterization and regulatory mechanisms of specific ZmWAKL genes involved in maize kernel development, offering prospects for their utilization in maize breeding programs.

STRESS INDUCED FACTOR 2 Regulates Arabidopsis Stomatal Immunity through Phosphorylation of the Anion Channel SLAC1.

Upon recognition of microbes, pattern recognition receptors (PRRs) activate pattern-triggered immunity. FLAGELLIN SENSING2 (FLS2) and BRASSINOSTEROID INSENSITIVE1-ASSOCIATED KINASE1 (BAK1) form a typical PRR complex that senses bacteria. Here, we report that the kinase activity of the malectin-like receptor-like kinase STRESS INDUCED FACTOR 2 (SIF2) is critical for Arabidopsis (Arabidopsis thaliana) resistance to bacteria by regulating stomatal immunity. SIF2 physically associates with the FLS2-BAK1 PRR complex and interacts with and phosphorylates the guard cell SLOW ANION CHANNEL1 (SLAC1), which is necessary for abscisic acid (ABA)-mediated stomatal closure. SIF2 is also required for the activation of ABA-induced S-type anion currents in Arabidopsis protoplasts, and SIF2 is sufficient to activate SLAC1 anion channels in Xenopus oocytes. SIF2-mediated activation of SLAC1 depends on specific phosphorylation of Ser 65. This work reveals that SIF2 functions between the FLS2-BAK1 initial immunity receptor complex and the final actuator SLAC1 in stomatal immunity.

Deficiency of the Tbc1d21 gene causes male infertility with morphological abnormalities of the sperm mitochondria and flagellum in mice.

Approximately 2-15% of couples experience infertility, and around half of these cases are attributed to male infertility. We previously identified TBC1D21 as a sterility-related RabGAP gene derived from infertile men. However, the in vivo function of TBC1D21 in male fertility remains unclear. Here, we show that loss of Tbc1d21 in mice resulted in male infertility, characterized by defects in sperm tail structure and diminished sperm motility. The mitochondria of the sperm-tail had an abnormal irregular arrangement, abnormal diameter, and structural defects. Moreover, the axoneme structure of sperm tails was severely disturbed. Several TBC1D21 interactors were selected via proteomic analysis and functional grouping. Two of the candidate interactors, a subunit protein of translocase in the outer membrane of mitochondria (TOMM20) and an inner arm component of the sperm tail axoneme (Dynein Heavy chain 7, DNAH7), confirmed in vivo physical co-localization with TBC1D21. In addition, TOMM20 and DNAH7 detached and dispersed outside the axoneme in Tbc1d21-deficient sperm, instead of aligning with the axoneme. From a clinical perspective, the transcript levels of TBC1D21 in sperm from teratozoospermia cases were significantly reduced when compared with those in normozoospermia. We concluded that TBC1D21 is critical for mitochondrial and axoneme development of mammalian sperm.

Blocking vicious cycle of cardiac dysfunction by external cardiopulmonary resuscitation is the key to rescue acute aluminium phosphide poisoning.

Aluminium phosphide (ALP) and aluminium zinc phosphide (ZnP), the two main ingredients of fumigation drugs, are commonly used to kill insects or rodents in grain. When exposed to water, highly toxic phosphine gas is released and absorbed through the respiratory or digestive tract. Phosphine gas could non-selectively block cytochrome oxidase, inhibit electron transfer and suppress oxidative phosphorylation, leading to cellular hypoxia and organ dysfunction. The characteristic clinical manifestations are refractory shock and metabolic acidosis with high mortality. However, patients with ALP poisoning have a chance to be cured. Here, we report a case of oral ALP poisoning that was successfully treated by extracorporeal membrane oxygenation (ECMO) combined with continuous renal replacement therapy (CRRT) during frequent ventricular fibrillation and cardiac dysfunction.

[Interpretation of the key updates in the 2022 European guideline on the management of neonatal respiratory distress syndrome]. / 2022年欧洲新生儿呼吸窘迫综合征管理指南更新要点解读.

With the deepening of clinical research, the management of neonatal respiratory distress syndrome (RDS) needs to be optimized and improved. This article aims to introduce the 2022 European guideline on the management of neonatal RDS, focusing on its key updates. The guide has optimized the management of risk prediction for preterm birth, maternal referral, application of prenatal corticosteroids, application of lung protective ventilation strategies, and general care for infants with RDS. The guideline is mainly applicable to the management of RDS in neonates with gestational age greater than 24 weeks.

Cellulose synthase-like protein OsCSLD4 plays an important role in the response of rice to salt stress by mediating abscisic acid biosynthesis to regulate osmotic stress tolerance.

Cell wall polysaccharide biosynthesis enzymes play important roles in plant growth, development and stress responses. The functions of cell wall polysaccharide synthesis enzymes in plant growth and development have been well studied. In contrast, their roles in plant responses to environmental stress are poorly understood. Previous studies have demonstrated that the rice cell wall cellulose synthase-like D4 protein (OsCSLD4) is involved in cell wall polysaccharide synthesis and is important for rice growth and development. This study demonstrated that the OsCSLD4 function-disrupted mutant nd1 was sensitive to salt stress, but insensitive to abscisic acid (ABA). The expression of some ABA synthesis and response genes was repressed in nd1 under both normal and salt stress conditions. Exogenous ABA can restore nd1-impaired salt stress tolerance. Moreover, overexpression of OsCSLD4 can enhance rice ABA synthesis gene expression, increase ABA content and improve rice salt tolerance, thus implying that OsCSLD4-regulated rice salt stress tolerance is mediated by ABA synthesis. Additionally, nd1 decreased rice tolerance to osmotic stress, but not ion toxic tolerance. The results from the transcriptome analysis showed that more osmotic stress-responsive genes were impaired in nd1 than salt stress-responsive genes, thus indicating that OsCSLD4 is involved in rice salt stress response through an ABA-induced osmotic response pathway. Intriguingly, the disruption of OsCSLD4 function decreased grain width and weight, while overexpression of OsCSLD4 increased grain width and weight. Taken together, this study demonstrates a novel plant salt stress adaptation mechanism by which crops can coordinate salt stress tolerance and yield.

Genome-Wide Characterization and Phylogenetic Analysis of GSK Genes in Maize and Elucidation of Their General Role in Interaction with BZR1.

Glycogen synthase kinase-3 (GSK-3) is a nonreceptor serine/threonine protein kinase that is involved in diverse processes, including cell development, photomorphogenesis, biotic and abiotic stress responses, and hormone signaling. In contrast with the deeply researched GSK family in Arabidopsis and rice, maize GSKs' common bioinformatic features and protein functions are poorly understood. In this study, we identified 11 GSK genes in the maize (Zea mays L.) genome via homologous alignment, which we named Zeama;GSKs (ZmGSKs). The results of ZmGSK protein sequences, conserved motifs, and gene structures showed high similarities with each other. The phylogenetic analyses showed that a total of 11 genes from maize were divided into four clades. Furthermore, semi-quantitative RT-PCR analysis of the GSKs genes showed that ZmGSK1, ZmGSK2, ZmGSK4, ZmGSK5, ZmGSK8, ZmGSK9, ZmGSK10, and ZmGSK11 were expressed in all tissues; ZmGSK3, ZmGSK6, and ZmGSK7 were expressed in a specific organization. In addition, GSK expression profiles under hormone treatments demonstrated that the ZmGSK genes were induced under BR conditions, except for ZmGSK2 and ZmGSK5. ZmGSK genes were regulated under ABA conditions, except for ZmGSK1 and ZmGSK8. Finally, using the yeast two-hybrid and BiFC assay, we determined that clads II (ZmGSK1, ZmGSK4, ZmGSK7, ZmGSK8, and ZmGSK11) could interact with ZmBZR1. The results suggest that clade II of ZmGSKs is important for BR signaling and that ZmGSK1 may play a dominant role in BR signaling as the counterpart to BIN2. This study provides a foundation for the further study of GSK3 functions and could be helpful in devising strategies for improving maize.

Designing a 0D/1D S-Scheme Heterojunction of Cadmium Selenide and Polymeric Carbon Nitride for Photocatalytic Water Splitting and Carbon Dioxide Reduction.

Constructing photocatalysts to promote hydrogen evolution and carbon dioxide photoreduction into solar fuels is of vital importance. The design and establishment of an S-scheme heterojunction system is one of the most feasible approaches to facilitate the separation and transfer of photogenerated charge carriers and obtain powerful photoredox capabilities for boosting photocatalytic performance. Herein, a zero-dimensional/one-dimensional S-scheme heterojunction composed of CdSe quantum dots and polymeric carbon nitride nanorods (CdSe/CN) is created and constructed via a linker-assisted hybridization approach. The CdSe/CN composites exhibit superior photocatalytic activity in water splitting and promoted carbon dioxide conversion performance compared with CN nanorods and CdSe quantum dots. The best efficiency in photocatalytic water splitting (10.2% apparent quantum yield at 420 nm irradiation, 20.1 mmol g-1 h-1 hydrogen evolution rate) and CO2 reduction (0.77 mmol g-1 h-1 CO production rate) was achieved by 5%CdSe/CN composites. The significantly improved photocatalytic reactivity of CdSe/CN composites primarily originates from the emergence of an internal electric field in the zero-dimensional/one-dimensional S-scheme heterojunction, which could greatly improve the photoinduced charge-carrier separation. This work underlines the possibility of employing polymeric carbon nitride nanostructures as appropriate platforms to establish highly active S-scheme heterojunction photocatalysts for solar fuel production.

Degradation performance of high-concentration coking wastewater by manganese oxide ore acidic oxidation.

The degradation of coking wastewater using a manganese oxide ore acidic oxidation was investigated. This work was performed in three stages. Firstly, the advantageous degradation conditions were measured by the degradation tests, and under the optimal conditions percentage degradation was obtained of 91.6% chemical oxygen demand measured by potassium dichromate oxidation (CODcr), 94.7% total nitrogen (TN), 98.3% phenols, 98.2% fatty acid, 89.5% tar, and 98.9% sulphide for the oxidized effluent, simultaneously cogenerating a Mn2+concentration of 46.2 g/L for Mn-electrolytic stock solution. Secondly, the transformation analysis of the special chemical group of coking wastewater contaminants illustrated that the employment of manganese oxide ore generated the degradation of low and high molecular weight organics, especially causing polymers to break down into oligomers. Thirdly, the electrochemical characteristics of the interface between wastewater and ore revealed that the contaminant degradation of coking wastewater greatly depended on the oxidation capacity of the surface oxide species, involving a simple answer to the MnO2 oxidation for small-molecule organic materials and a strengthening response to the MnO·OH oxidation for high-weight molecule organic substances. The treatment of coking wastewater using the Mn-oxide ore acidic oxidation process is an effective and value-added method, which is particularly applicable to high-concentration coking wastewater.

Localization Patterns of RAB3C Are Associated with Murine and Human Sperm Formation.

Background and Objectives: Septins (SEPTs) are highly conserved GTP-binding proteins and the fourth component of the cytoskeleton. Polymerization of SEPTs contributes to several critical cellular processes such as cytokinesis, cytoskeletal remodeling, and vesicle transportation. In our previous study, we found that SEPT14 mutations resulted in teratozoospermia with >87% sperm morphological defects. SEPT14 interactors were also identified through proteomic assays, and one of the peptides was mapped to RAB3B and RAB3C. Most studies on the RAB3 family have focused on RAB3A, which regulates the exocytosis of neurotransmitters and acrosome reactions. However, the general expression and patterns of the RAB3 family members during human spermatogenesis, and the association between RAB3 and teratozoospermia owing to a SEPT14 mutation, are largely unknown. Materials and Methods: Human sperm and murine male germ cells were collected in this study and immunofluorescence analysis was applied on the collected sperm. Results: In this study, we observed that the RAB3C transcripts were more abundant than those of RAB3A, 3B, and 3D in human testicular tissues. During human spermatogenesis, the RAB3C protein is mainly enriched in elongated spermatids, and RAB3B is undetectable. In mature human spermatozoa, RAB3C is concentrated in the postacrosomal region, neck, and midpiece. The RAB3C signals were delocalized within human spermatozoa harboring the SEPT14 mutation, and the decreased signals were accompanied by a defective head and tail, compared with the healthy controls. To determine whether RAB3C is involved in the morphological formation of the head and tail of the sperm, we separated murine testicular tissue and isolated elongated spermatids for further study. We found that RAB3C is particularly expressed in the manchette structure, which assists sperm head shaping at the spermatid head, and is also localized at the sperm tail. Conclusions: Based on these results, we suggest that the localization of RAB3C proteins in murine and human sperm is associated with SEPT14 mutation-induced morphological defects in sperm.

The effect of lipocalin-2 (LCN2) on apoptosis: a proteomics analysis study in an LCN2 deficient mouse model.

BACKGROUND: Recent studies have shown that lipocalin-2 (LCN2) has multiple functions involved in various biological and pathological processes including energy homeostasis, cancer, inflammation, and apoptosis. We aimed to investigate the effect of LCN2 on apoptosis that influences the pathogenetic process of metabolic diseases and cancer. METHODS: We performed a proteomics analysis of livers taken from LCN2-knockout mice and wild type mice by using label-free LC-MS/MS quantitative proteomics. RESULTS: Proteomic analysis revealed that there were 132 significantly differentially expressed proteins (49 upregulated and 83 downregulated) among 2140 proteins in the liver of LCN2-knockout mice compared with wild type mice. Of these, seven apoptosis-associated proteins were significantly upregulated and seven apoptosis-associated proteins downregulated. CONCLUSION: Proteomics demonstrated that there were seven upregulated and seven downregulated apoptosis-associated proteins in liver of LCN2-knockout mice. It is important to clarify the effect of LCN2 on apoptosis that might contribute to the pathogenesis of insulin resistance, cancer, and various nervous system diseases.

Genome-wide identification of ZmSnRK2 genes and functional analysis of ZmSnRK2.10 in ABA signaling pathway in maize (Zea mays L).

BACKGROUND: Phytohormone abscisic acid (ABA) is involved in the regulation of a wide range of biological processes. In Arabidopsis, it has been well-known that SnRK2s are the central components of the ABA signaling pathway that control the balance between plant growth and stress response, but the functions of ZmSnRK2 in maize are rarely reported. Therefore, the study of ZmSnRK2 is of great importance to understand the ABA signaling pathways in maize. RESULTS: In this study, 14 ZmSnRK2 genes were identified in the latest version of maize genome database. Phylogenetic analysis revealed that ZmSnRK2s are divided into three subclasses based on their diversity of C-terminal domains. The exon-intron structures, phylogenetic, synteny and collinearity analysis indicated that SnRK2s, especially the subclass III of SnRK2, are evolutionally conserved in maize, rice and Arabidopsis. Subcellular localization showed that ZmSnRK2 proteins are localized in the nucleus and cytoplasm. The RNA-Seq datasets and qRT-PCR analysis showed that ZmSnRK2 genes exhibit spatial and temporal expression patterns during the growth and development of different maize tissues, and the transcript levels of some ZmSnRK2 genes in kernel are significantly induced by ABA and sucrose treatment. In addition, we found that ZmSnRK2.10, which belongs to subclass III, is highly expressed in kernel and activated by ABA. Overexpression of ZmSnRK2.10 partially rescued the ABA-insensitive phenotype of snrk2.2/2.3 double and snrk2.2/2.3/2.6 triple mutants and led to delaying plant flowering in Arabidopsis. CONCLUSION: The SnRK2 gene family exhibits a high evolutionary conservation and has expanded with whole-genome duplication events in plants. The ZmSnRK2s expanded in maize with whole-genome and segmental duplication, not tandem duplication. The expression pattern analysis of ZmSnRK2s in maize offers important information to study their functions. Study of the functions of ZmSnRK.10 in Arabidopsis suggests that the ABA-dependent members of SnRK2s are evolutionarily conserved in plants. Our study elucidated the structure and evolution of SnRK2 genes in plants and provided a basis for the functional study of ZmSnRK2s protein in maize.

Outcome-based student assessment enhances academic performance in basic medical laboratory course.

Basic medical laboratory courses (BMLCs) play an important role in medical educational courses helping the student acquire three important skills of surgical operating, collaborative learning, and problem solving. The outcome-based student assessment (OBSA) is a learning evaluation method that establishes specific evaluation points based on performance of students in three aspects: surgical operating, collaborative learning, and problem solving in the BMLC curriculum practices. The purpose of the present randomized controlled trial study is to explore the efficiency of OBSA program in BMLCs. The 233 students attending BMLCs were randomly divided into 2 groups, 118 in the OBSA group and 115 in the control group. We conducted multiple-choice examination questions (MCQs) test and two questionnaires with the method of two-sample t test for statistics. The results of MCQs in total eight BMLC blocks showed that the academic performance of the OBSA group was significantly better than that of the control group (P < 0.05). In addition, the average scores of direct observation of procedural skills (DOPS) and mini-experimental evaluation exercise in OBSA group were significantly higher than those in control group (P < 0.05). The majority of the medical students preferred the OBSA and considered OBSA could effectively improve their surgical operating skills (83.9%), collaborative learning skills (92.1%), and problem-solving skills (91.1%). From the above, OBSA is an effective evaluation method for the implementation of the BMLC curriculum.

The prenatal ultrasonic character and postnatal follow-up of 227 microcystic and macrocystic congenital cystic adenomatoid malformations.

The objective of our study was to compare microcystic and macrocystic congenital cystic adenomatoid malformation (CCAMs) through prenatal characteristics, perinatal outcome, postnatal management and development after consultation in our prenatal diagnosis centre. We conducted a retrospective cohort study of 227 cases prenatally diagnosed as CCAM in our hospital within three years. One hundred and eighty-one cases continued their pregnancy and 46 pregnancies were terminated. One hundred and fifteen of 227 cases were microcystic and 112 were macrocystic. The prenatal ultrasound characteristics of two types showed no statistically significant differences, despite that CVR of macrocystic CCAMs was mildly greater than microcystic. None of recorded cases received surgical intervention in utero. Compared with healthy foetuses, CCAMs presented with higher percentage of polyhydramnios and male foetuses, larger amount of postpartum blood loss and longer duration of NICU hospitalisation. Compared with 46 legal abortions, continued pregnancy cases had a smaller CVR, less polyhydramnios, cardiac shift and hydrops. One hundred and seventy-nine cases were followed up after birth and 174 babies were asymptomatic. Thirty one cases received successful surgical resection. In conclusion, the prenatally diagnosed CCAMs have a good short-term prognosis and conservative management is a reasonable option in asymptomatic fetuses. Microcystic and macrocystic CCAMs both presented similar prenatal courses and perinatal prognoses. Conservative management, prenatally and postnatally, could be accepted in selected cases.Impact statementWhat is already known on this subject? Congenital cystic adenomatoid malformation is a well-known developmental abnormality of the lung. The prognosis for most CCAMs is good, but the prenatal and postnatal management remains controversial.What do the results of this study add? This study is one of the largest case cohorts to conclude that microcystic and macrocystic CCAMs both presented similar prenatal courses and perinatal prognoses. Conservative management is a reasonable option in asymptomatic babies.What are the implications of these findings for clinical practice and/or further research? A comprehensive assessment by an experienced multidisciplinary team is necessary to forbid blinding abortions of CCAMs. Conservative management prenatally and postnatally could be accepted in most asymptomatic cases.

[Factors Related to Successful Ventilator Weaning in Respiratory Care Center Patients: A Retrospective Chart Review Study].

BACKGROUND: The subacute respiratory care unit is an important relay station where respirator-dependent patients may access subsequent chronic respiratory care. Although there is relatively little information in the literature regarding respirator disconnections in subacute respiratory care units, assisting patients to disconnect successfully from respirators is a primary challenge for care teams. PURPOSE: The purpose of this study was to understand respirator disconnections and the factors affecting these events in subacute respiratory care units to improve the effectiveness of ventilator weaning and reduce the burden on families and medical care providers. METHODS: This was a retrospective chart review study. Patients admitted to the subacute respiratory care unit for respiratory training during the study period from January 2016 to December 2019 were recruited as subjects and the data were collected from the Chang Gung Medical Research Database`s health insurance secondary data using a self-made transcription form. RESULTS: The ventilator weaning success rate of the subjects in this study was 78.5%. A bivariate analysis revealed that consciousness status; disease severity; rapid shallow breathing index; days of hospitalization in a respiratory care center; days of ventilator use; blood urea nitrogen, white blood cell, hemoglobin, and blood albumin levels; and mean caloric intake were each significantly associated with successful ventilator withdrawal. The predictors of ventilator weaning in respiratory care center patients were identified as disease severity, rapid shallow breathing index, days of ventilator use, white blood cell level, and hemoglobin level. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Respirator-dependent patients should be evaluated and monitored as early as possible. Moreover, a ventilator weaning plan should be included as a regular testing and monitoring item. Also, a respirator removal program should be provided on a case-by-case basis. Individualized ventilator weaning programs may reduce the burden on families and medical care providers.

Dual-Specificity Phosphatase 9 Protects Against Nonalcoholic Fatty Liver Disease in Mice Through ASK1 Suppression.

Nonalcoholic fatty liver disease (NAFLD), ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), is the leading cause of chronic liver diseases. Until now, no medications for NAFLD have been approved by relevant governmental agencies. Dual-specificity phosphatase 9 (Dusp9) is a member of the DUSP protein family. Dusp9 is expressed in insulin-sensitive tissues, and its expression may be modified with the development of insulin resistance (IR). However, the molecular targets and mechanisms of Dusp9 action on NAFLD and NASH remain poorly understood. In this study, using conditional liver-specific Dusp9-knockout (Dusp9-CKO) mice and Dusp9-transgenic mice, we showed that Dusp9 was a key suppressor of high-fat diet-induced hepatic steatosis and inflammatory responses and that Dusp9 deficiency aggravated high-fat high-cholesterol diet-induced liver fibrosis. Dusp9 was shown to exert its effects by blocking apoptosis signal-regulating kinase 1 (ASK1) phosphorylation and the subsequent activation of p38 and c-Jun NH2-terminal kinase signaling. Conclusion: Hepatocyte Dusp9 prevents NAFLD and NASH progression in mice, including lipid accumulation, glucose metabolism disorders, and enhanced inflammation and liver fibrosis, in an ASK1-dependent manner; these findings suggest that Dusp9 may be a promising therapeutic target for the treatment of NAFLD and NASH.