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.

Antibody-drug conjugates targeting HER2 for the treatment of urothelial carcinoma: potential therapies for HER2-positive urothelial carcinoma.

Urothelial carcinoma (UC) is a common cancer characterized by high morbidity and mortality rates. Despite advancements in treatment, challenges such as recurrence and low response rates persist. Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic approach for various cancers, although their application in UC is currently limited. This review focuses on recent research regarding ADCs designed to treat UC by targeting human epidermal growth factor receptor 2 (HER2), a surface antigen expressed on tumor cells. ADCs comprise three main components: an antibody, a linker, and a cytotoxic payload. The antibody selectively binds to tumor cell surface antigens, facilitating targeted delivery of the cytotoxic drug, while linkers play a crucial role in ensuring stability and controlled release of the payload. Cleavable linkers release the drug within tumor cells, while non-cleavable linkers ensure stability during circulation. The cytotoxic payload exerts its antitumor effect by disrupting cellular pathways. HER2 is commonly overexpressed in UCs, making it a potential therapeutic target. Several ADCs targeting HER2 have been approved for cancer treatment, but their use in UC is still being tested. Numerous HER2 ADCs have demonstrated significant growth inhibition and induction of apoptosis in translational models of HER2-overexpressing bladder cancer. Ongoing clinical trials are assessing the efficacy and safety of ADCs targeting HER2 in UC, with the aim of determining tumor response and the potential of ADCs as a treatment option for UC patients. The development of effective therapies with improved response rates and long-term effectiveness is crucial for advanced and metastatic UC. ADCs targeting HER2 show promise in this regard and merit further investigation for UC treatment.

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.

Decreased Klotho Expression Causes Accelerated Decline of Male Fecundity through Oxidative Injury in Murine Testis.

Oxidative stress is the etiology for 30-80% of male patients affected by infertility, which is a major health problem worldwide. Klotho protein is an aging suppressor that functions as a humoral factor modulating various cellular processes including antioxidation and anti-inflammation, and its dysregulation leads to human pathologies. Male mice lacking Klotho are sterile, and decreased Klotho levels in the serum are observed in men suffering from infertility with lower sperm counts. However, the mechanism by which Klotho maintains healthy male fertility remains unclear. Klotho haplodeficiency (Kl+/-) accelerates fertility reduction by impairing sperm quality and spermatogenesis in Kl+/- mice. Testicular proteomic analysis revealed that loss of Klotho predominantly disturbed oxidation and the glutathione-related pathway. We further focused on the glutathione-S-transferase (GST) family which counteracts oxidative stress in most cell types and closely relates with fertility. Several GST proteins, including GSTP1, GSTO2, and GSTK1, were significantly downregulated, which subsequently resulted in increased levels of the lipid peroxidation product 4-hydroxynonenal and apoptosis in murine testis with low or no expression of Klotho. Taken together, the loss of one Kl allele accelerates male fecundity loss because diminished antioxidant capability induces oxidative injury in mice. This is the first study that highlights a connection between Klotho and GST proteins.

Identification of the Hepatic Metabolites of Flumazenil and their Kinetic Application in Neuroimaging.

Studies of the neurobiological causes of anxiety disorders have suggested that the γ-aminobutyric acid (GABA) system increases synaptic concentrations and enhances the affinity of GABAA (type A) receptors for benzodiazepine ligands. Flumazenil antagonizes the benzodiazepine-binding site of the GABA/benzodiazepine receptor (BZR) complex in the central nervous system (CNS). The investigation of flumazenil metabolites using liquid chromatography (LC)-tandem mass spectrometry will provide a complete understanding of the in vivo metabolism of flumazenil and accelerate radiopharmaceutical inspection and registration. The main goal of this study was to investigate the use of reversed-phase high performance liquid chromatography (PR-HPLC), coupled with electrospray ionization triple-quadrupole tandem mass spectrometry (ESI-QqQ MS), to identify flumazenil and its metabolites in the hepatic matrix. Carrier-free nucleophilic fluorination with an automatic synthesizer for [18F]flumazenil, combined with nano-positron emission tomography (NanoPET)/computed tomography (CT) imaging, was used to predict the biodistribution in normal rats. The study showed that 50% of the flumazenil was biotransformed by the rat liver homogenate in 60 min, whereas one metabolite (M1) was a methyl transesterification product of flumazenil. In the rat liver microsomal system, two metabolites were identified (M2 and M3), as their carboxylic acid and hydroxylated ethyl ester forms between 10 and 120 min, respectively. A total of 10-30 min post-injection of [18F]flumazenil showed an immediate decreased in the distribution ratio observed in the plasma. Nevertheless, a higher ratio of the complete [18F]flumazenil compound could be used for subsequent animal studies. [18F] According to in vivo nanoPET/CT imaging and ex vivo biodistribution assays, flumazenil also showed significant effects on GABAA receptor availability in the amygdala, prefrontal cortex, cortex, and hippocampus in the rat brain, indicating the formation of metabolites. We reported the completion of the biotransformation of flumazenil by the hepatic system, as well as [18F]flumazenil's potential as an ideal ligand and PET agent for the determination of the GABAA/BZR complex for multiplex neurological syndromes at the clinical stage.

Current Surgical Treatment for Neurogenic Lower Urinary Tract Dysfunction in Patients with Chronic Spinal Cord Injury.

This study aimed to present a comprehensive literature review of the efforts of a spinal cord injury workgroup in Taiwan regarding urologic surgery for neurogenic lower urinary tract dysfunction (NLUTD) in patients with chronic spinal cord injury (SCI). Surgical procedures should be viewed as a final option for managing patients with SCI who have persistent symptoms and complications that cannot be resolved by other means. Surgeries can be grouped according to their purpose: reducing bladder pressures, reducing urethra resistance, increasing urethra resistance, and urinary diversion. The choice of surgery depends on the type of LUTD based on urodynamic tests. Additionally, cognitive function, hand motility, comorbidities, efficacy of surgery, and related complications should be considered.

[Celebrating the 70th Anniversary of The Journal of Nursing].

The Journal of Nursing (JN) was first published in Taiwan seventy years ago in 1953 under its former name, Nursing Quarterly. The first issue of JN under its current name was published in 1961. JN mainly publishes academic papers. Despite the vicissitudes of history, the Taiwan Nurses Association (TWNA) remained true to its mission of serving its members, and resumed publication of JN after relocating to Taiwan from China after 1949. JN articles published over the past seven decades have focused on promoting professional competence, advocating clinical practice, advancing nursing education, introducing new concepts of administrative reform, and disseminating research findings and clinical case reports with goals of promoting nurses' understanding of nursing professional theory, cultivating critical thinking and creativity, helping nurses acquire and accumulate knowledge and skills in scientific language, and solving problems encountered in clinical care and education. In addition, in response to advances in medical care and the COVID-19 pandemic, the content of JN published in 2020 highlighted the current pandemic situation in special articles, research, and case reports to provide readers with knowledge about related care and research results. Through the publication of journal papers, we are promoting more interactions and inspiring more sparks of insight. JN is valued by readers around the world because the contributions and support of its many authors have allowed the journal to grow and thrive. At the same time, I would also like to thank the editor of each topic for their enthusiasm and enthusiastic welcoming of manuscript contributions and all Review Committee members for their careful review of manuscripts and tireless modification and review of articles, so as to provide readers with reliable reference resources. Therefore, the quality of the content published in JN has been recognized globally, and has been successively indexed in the globally recognized databases, including MEDLINE/PubMed (indexed from 2004), CINAHL (Cumulative Index to Nursing & Allied Health Literature; indexed from 1996), EBSCO Publishing (indexed from 2002), Scopus (indexed from 2004), ProQuest (indexed from 2012), and Airiti Library (indexed from 2004). Moreover, JN has been a RIHSS-accredited tier three journal since 2019. In addition, JN has won awards for five consecutive years since 2017. The excellent content quality of JN has made it an important source of knowledge dissemination and influence in domestic academic circles. Since becoming Editor-in-Chief of JN, I have read many contributors' articles and feel regularly grateful to the authors for their submissions, whether their articles are accepted for publication or not. With the efforts of previous Editors-in-Chief and Editorial Committee members, JN has continuously adjusted its mode of operations to meet social changes and has gradually established a comprehensive process for submission, review and publication. In recognition of JN's 70th anniversary in publication, we look forward to continued, sustainable development of the journal and of service for our global readership. We look forward for JN to do even more in the coming decade and beyond!

[The Effects of Supportive Caring on Symptoms Distress, Nursing Needs, and Depression in Patients With Brain Tumor After Surgery: A Preliminary Study].

BACKGROUND: Brain tumors are mainly treated with surgery. However, patients still experience many symptoms and nursing needs due to disease and treatment-related factors that, if not improved in a timely manner, may result in depression. PURPOSE: The purpose of this study was to examine the effectiveness of supportive caring on symptom distress, nursing needs, and depressive symptoms in patients with brain tumor after surgery. METHODS: This study adopted a two-group, pre- and post-test experimental design. The enrolled participants were randomized into two groups. Those in the experimental group received a phone-based supportive caring intervention twice at 1 and 3 months after surgery. Those in the control group received usual discharge care. The measurement outcomes included a supportive care needs survey, symptom distress scales, and the center for epidemiological studies of depression. Baseline data was collected prior to hospital discharge (T0), with follow-up data collected at one month (T1), three months (T2), and six months (T3) after surgery. RESULTS: The results of the generalized estimating equation analysis showed that nursing needs in the experimental group at T1 (ß = -23.61, p < .001), T2 (ß = -22.51, p < .001), and T3 (ß = -22.26, p < .001) were significant lower than in the control group. Also, symptom distress in the experimental group at T1 (ß = -7.03, p = .019) and T2 (ß = -8.39, p = .003) was significantly lower than in the control group. However, depressive symptoms in the experimental group were lower than in the control group only at T2 (ß = -8.55, p = .005). CONCLUSIONS: The results of this study confirm that supportive care helps improve nursing needs, symptoms distress, and depressive symptoms in patients with brain tumor after surgery. Medical team members should pay attention to these issues following surgery.

[The Spread of the Epidemic Among Vulnerable Groups and Related Epidemic Prevention Issues].

The COVID-19 pandemic has highlighted the adverse health, economic and social consequences of longstanding social inequality on various communities, groups, and individuals. Because they lack sufficient access to health and social resources, vulnerable groups affected by lower incomes, geographic remoteness, and/or low awareness of disease prevention and control measures are more susceptible to infection (McDonald, 2022; Mein, 2020; Moghanibashi-Mansourieh, 2021). According to The Lancet (2020) editorial board, vulnerable groups are defined as segments of the population disproportionately exposed to risk. People not considered vulnerable at the start of the pandemic may become vulnerable afterward due to pandemic-related effects such as loss of income and lack of access to social support. Thus, during the COVID-19 pandemic, vulnerable groups include not only traditionally vulnerable populations (e.g., older adults, infants, immuno-compromised individuals) but socioeconomic groups that may be financially, mentally, or physically struggling to cope. In addition, schools of all levels around the world have adopted remote online synchronous or asynchronous teaching methods to avoid pandemic-related school closures and interruptions in student learning (Dreesen et al., 2020). However, issues such as the accessibility, availability, acceptability, and applicability of online learning equipment for vulnerable students should be comprehensively considered by the government. Governments encounter multiple challenges related to the above-mentioned issues, including (1) dealing with the public health effects of the pandemic crisis; (2) dealing with related economic and social impacts such as social and economic depression due to isolation, tax reductions, increased payments, subsidies, compensation, and the provision of unemployment insurance (Moghanibashi-Mansourieh, 2021); and (3) reforming education teaching methods and providing appropriate information and equipment of vulnerable groups. In responding to COVID-19, policymakers should consider the risks of exacerbating the inequalities faced by vulnerable groups. Moreover, vulnerable groups should be clearly identified to limit the long-term consequences of the pandemic. Governments must continually identify vulnerable / at-risk populations and provide equitable support to those most at risk.

[Human Health Rights: Discussing Health Inequality for Taiwanese Indigenous Peoples and the Appropriateness of Current Epidemic Policies].

Many studies from around the world demonstrate that COVID-19 has had significantly higher rates of infection, hospitalization, and mortality among indigenous and other vulnerable groups than among mainstream population groups. This situation has exposed and reinforced pre-existing health inequalities. This article investigates the rates of infection and mortality among different cultural groups during the COVID-19 pandemic, and then deconstructs the key elements related to systemic or structural racism. The impacts on the human rights and health of indigenous peoples and issues of policy formulation and resource equity during the epidemic are also mentioned. Based on the identified root causes of health inequality, suggestions for reducing health inequality for Taiwanese indigenous peoples are proposed. Further, during epidemics, policymakers must design and implement culturally appropriate epidemic prevention policies, systems, and strategies for indigenous and other disadvantaged populations.

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.

[Analysis of the Effects of Femoral Nerve Block on Pain Level and Knee Mobility in Patients With Total Knee Replacement].

BACKGROUND: Osteoarthritis is a common cause of inactivity and reduced quality of life in the elderly. Total knee replacement (TKR) surgery, a last-stage treatment option for osteoarthritis, often results in postoperative pain that influences knee flexion and the ability to perform prescribed rehabilitation exercises. PURPOSE: This study was designed to examine the effectiveness of single femoral nerve block (FNB) on pain level and knee mobility in patients with TKR. METHODS: A quasi-experimental, two-group, longitudinal study was designed. The participants were distributed into the FNB group (n = 86) and non-FNB group (n = 86). The outcome measurements included pain scale (Numerical Rating Scale) score and knee continuous passive motion knee flexion angle. The five assessments and followed-up times were as follows: admission day (T0) and post-surgery day 1, 2, 3, and 4. RESULTS: The results of the generalized estimating equations model showed that the pain level in the FNB group was significantly lower than in the non-FNB group, (p < .001). In terms of analgesics demand from post-surgery day 1 to day 4, the FNB group exhibited a significantly lower demand than the non-FNB group (p < .01). In addition, significant differences in the continuous passive motion rehabilitation exercise angle were found between the two groups from post-surgery day 1 through day 4 (p < .05). Finally, significant differences in knee flexion angles between the two groups were observed between hospital admission and discharge (p < .001). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The findings of this study support the positive effects of the femoral nerve block intervention on patients who receive total knee replacement surgery. The results were significant in terms of pain relief and knee mobility recovery. This intervention should be made available for use in the clinical care of TKR patients.

Comparison of oncological outcomes for hand-assisted and pure laparoscopic radical nephroureterectomy: results from the Taiwan Upper Tract Urothelial Cancer Collaboration Group.

PURPOSE: Laparoscopic radical nephroureterectomy (LNU) has gradually become the new standard treatment for localized upper tract urothelial cancer (UTUC). With more blunt dissection and tactile sensation, hand-assisted LNU might shorten the operative time compared with the pure laparoscopic approach. However, whether the use of the hand-assisted or the pure laparoscopic approach has an effect on oncological outcomes remains unclear. METHODS: We retrospectively identified 629 patients with non-metastatic UTUC who underwent hand-assisted (n = 515) or pure LNU (n = 114) at 9 hospitals in Taiwan between 2004 and 2019. Overall survival, cancer-specific survival, recurrence-free survival, and bladder recurrence-free survival were compared between these two groups using inverse-probability of treatment weighting (IPTW) derived from the propensity scores for baseline covariate adjustment. RESULTS: The median follow-up period was 32.9 and 28.7 months in the hand-assisted and the pure groups, respectively. IPTW-adjusted Cox proportional hazards models showed that the laparoscopic approach (pure vs. hand-assisted) was not significantly associated with all-cause mortality (HR 0.79, 95% CI 0.49-1.24, p = 0.304), cancer-specific mortality (HR 0.88, 95% CI 0.51-1.51, p = 0.634), or extra-vesical recurrence (HR 0.65, 95% CI 0.41-1.04, p = 0.071). However, the pure laparoscopic approach was significantly associated with lower intra-vescial recurrence (HR 0.64, 95% CI 0.43-0.96, p = 0.029) for patients who underwent LNU. Kaplan-Meier curves also revealed that the pure laparoscopic approach was associated with better bladder recurrence-free survival compared with the hand-assisted laparoscopic approach in both the original cohort and the IPTW-adjusted cohort (log-rank p = 0.042 and 0.027, respectively). CONCLUSIONS: The performance of hand-assisted or pure LNU does not significantly affect the all-cause mortality, cancer-specific mortality, or extra-vesical recurrence for patients with non-metastatic UTUC. However, the hand-assisted laparoscopic approach could increase the risk of intra-vesical recurrence for patients who undergo LNU.

Tenofovir Hampers the Efficacy of Sorafenib in Prolonging Overall Survival in Hepatocellular Carcinoma.

Sorafenib is a first-line treatment for patients with advanced hepatocellular carcinoma (HCC). These patients may simultaneously receive anti-hepatitis B treatment if they are viremic. The N-Acetylgalactosaminyltransferase 14 (GALNT14) gene can serve as a biomarker to guide HCC treatments. However, the enzyme substrates of its gene product, GalNAc-T14 (a glycosyltransferase), remained uncharacterized. Here, we conducted a glycoproteome-wide search for GalNAc-T14 substrates using lectin affinity chromatography followed by tandem mass spectrometry. Seventeen novel GalNAc-T14 substrates were identified. A connective map analysis showed that an antiviral drug, tenofovir, was the leading medicinal compound to down-regulate the expression of these substrates. In vitro assays showed that HCC cells were resistant to sorafenib if pretreated by tenofovir but not entecavir. Clinical analysis showed that the concomitant use of tenofovir and sorafenib was a previously unrecognized predictive factor for unfavorable overall survival (hazard ratio = 2.060, 95% confidence interval = [1.256, 3.381], p = 0.004) in a cohort of 181 hepatitis-B-related, sorafenib-treated HCC patients (concomitant tenofovir versus entecavir treatment; p = 0.003). In conclusion, by conducting a glycoproteome-wide search for GalNAc-T14 substrates, we unexpectedly found that tenofovir was a major negative regulator of GalNAc-T14 substrates and an unfavorable anti-hepatitis B drug in HCC patients receiving sorafenib.

Psychometric Evaluation of the Nurses Professional Values Scale-3: Indonesian Version.

The Nurses Professional Values Scale-3 (NPVS-3) is an important instrument for measuring the development and sustainability of professional values in nurses and nursing students. The translation, adaptation, and validation on this scale, including in Indonesia, is still very limited. The purpose of this study was to examine the Indonesian version of NPVS-3. This study used forward and backward translation methods and a cluster random sampling of 600 nurses participated. The 28-item scale of NPVS3-I was tested using EFA, applying the principal axis factoring extraction method and varimax with Kaiser normalization rotation method. The CFA used SEM with AMOS. Findings suggested sufficient content validity, construct validity, and reliability of the Indonesian version of NPVS-3. The I-CVI values ranged between 0.80 to 1.00 and the S-CVI was 0.99. Construct validity was supported with loading factors ranging from 0.49 to 0.84 for three factors (Caring, Activism, and Professionalism). The CFA goodness-of-fit indices were X2 (df) = 1516.95 (347), p < 0.001, normed chi-square (X2/df) = 4.37, RMSEA = 0.106, SRMR = 0.079, and CFI = 0.735. The Indonesian version of the NPVS3 showed good internal consistency with Cronbach's alphas for the instrument of 0.97 and 0.94, 0.95, and 0.89 for Caring, Activism, and Professionalism, respectively. The Indonesian version of the NPVS-3 is valid and reliable for use in Indonesia.

Resveratrol inhibits MUC5AC expression by regulating SPDEF in lung cancer cells.

BACKGROUND: MUC5AC was recently identified to play important roles in the proliferation and metastasis of malignant mucinous lung tumor cells. Resveratrol (Res), a natural compound with anticancer effects in lung cancer cells, has been reported to inhibit mucin production in airway epithelial cells. This study aimed to investigate the inhibitory effect of Res on MUC5AC expression in lung mucinous adenocarcinoma cells and the potential mechanisms. METHODS: Mucus-producing A549 human lung carcinoma cells were used to test the effects of Res on SPDEF and MUC5AC expression. Gene and protein expression was assessed by real-time quantitative PCR (qPCR), immunofluorescence and western blotting assays. SPDEF lentivirus was used to upregulate SPDEF expression levels in mucus-producing A549 human lung carcinoma cells. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay. RESULTS: Res decreased MUC5AC expression in an SPDEF-dependent manner in mucus-producing A549 human lung carcinoma cells, and this change was accompanied by decreased ERK expression and AKT pathway activation. Moreover, SPDEF was found to be overexpressed in lung adenocarcinoma (LUAD), especially in mucinous adenocarcinoma. In-vitro functional assays showed that overexpression of SPDEF reduced the chemosensitivity of A549 cells to cisplatin (DDP). In addition, Res treatment increased A549 cell chemosensitivity to DDP by inhibiting the SPDEF-MUC5AC axis. CONCLUSION: Our results indicate that the SPDEF-MUC5AC axis is associated with DDP sensitivity, and that Res decreases SPDEF and MUC5AC expression by inhibiting ERK and AKT signaling in A549 cells, which provides a potential pharmacotherapy for the prevention and therapeutic management of mucinous adenocarcinoma.

[Nutritional Care in Acute and Chronic Illness].

Nutrition is essential for maintaining good health and preventing diseases, especially in patients suffering from acute or chronic diseases, infectious diseases, or critical illnesses because dietary intake involves both quantitative and qualitative changes and may disturb energy homeostasis (Richardson & Davidson, 2003). The metabolism of patients with critical illnesses is categorized as hypercatabolic, with significant loss of lean body tissue facilitated by the immune-neuroendocrine response of acute critical illness (Mechanick & Brett, 2005). Therefore, facing hunger during a period of physiological stress because of disease or treatment, results in an increased basal metabolic rate, accelerated protein breakdown, and increased energy and nutritional requirements in response to tissue damage, infection, and inflammation. This situation will develop rapidly into malnutrition or further exacerbate malnutrition because of inflammation and metabolic stress associated with diseases and injuries (Wortinger & Burns, 2015). The inflammatory response triggers the neurophysiology of patients and severely affects digestive behavior (Konsman & Dantzer, 2001), especially in terms of increasing demand for protein to provide amino acids for immunoglobulin and acute-phase protein production, both of which are fundamental to proper immune system functions. Under conditions of severe nutrient deficiency, the protein catabolism of the viscera and skeletal muscle for energy and protein generation will occur quickly in the acute phase. This catabolism has the potential to affect the cardiovascular, respiratory, immune, and all other body systems (Chan, 2015). Therefore, malnutrition during hospitalization may initiate immunosuppression and increase the risk of bacterial spread and sepsis, delayed wound healing, impaired organ function, prolonged hospitalization, and morbidity and mortality (Chan, 2015). As severe malnutrition is related to poor illness or treatment outcomes, which is associated with longer hospitalization and increased medical expenses, assessing patients' nutritional status and providing adequate nutritional care are critical. A nutritional assessment that includes body weight, physical condition and muscle condition, and calculation of resting energy requirements must be included as a standard part of the initial examination received by each patient. The results of this assessment should be considered together with the patient's illness status to formulate a nutritional care plan to provide the nutrition (energy, protein, essential fatty acids, and micronutrients) necessary to meet daily requirements, minimize metabolism, and break down proteins to support the immune system and wound healing (Chan, 2010). It is necessary to provide patients with full-spectrum nutrition and be aware that overeating may also cause metabolic and gastrointestinal complications, liver dysfunction, increased carbon dioxide production, and respiratory muscle weakness (Chan, 2010). Natural food should be provide the main source of nutrition as much as possible, and patients should be encouraged to eat a high-quality, complete diet. Although nutritionists may contribute to the assessment and design of nutritional plans for patients in clinical practice, their limited availability in hospitals disallows their providing the individualized attention required by each patient (Xu et al., 2017). Nurses have the most contact with patients and are most sensitive to their illness conditions. They are able to quickly assess the patient's nutritional needs according to changes in the situation, make referrals, and provide consultations on diet modifications. As the nutritional status of patients is involved in their treatment and physical recovery, nurses have always shouldered inter-professional responsibilities and played an essential role in the nutritional care of patients (Xu et al., 2017). For hospitalized patients and residents of long-term care institutions, nurses are able to pay attention to their nutritional related problems during the process of care, respond rapidly to nutrition-related treatment needs, and participate in the transdisciplinary professional team to prevent patient malnutrition.

[Enteral Feeding and Nutrition for Patients With Critical Illnesses].

Patients with critical illnesses often require nasogastric tube feeding (NG feeding) to support their nutritional and caloric-intake needs because of therapeutic issues and an inability to self-maintain proper nutritional intake. The four primary NG feeding methods include continuous feeding, cyclic feeding, intermittent feeding, and bolus feeding. Each method is unique in terms of timing and relative advantages and disadvantages. In this article, the related literature is reviewed to strengthen the correct concepts of clinical medical staff with regard to NG feeding and nutritional care for patients with critical illnesses with the ultimate goal of improving the quality of care provided to this vulnerable patient population.

ACTN4 Mediates SEPT14 Mutation-Induced Sperm Head Defects.

Septins (SEPTs) are highly conserved GTP-binding proteins and the fourth component of the cytoskeleton. Polymerized SEPTs participate in the modulation of various cellular processes, such as cytokinesis, cell polarity, and membrane dynamics, through their interactions with microtubules, actin, and other cellular components. The main objective of this study was to dissect the molecular pathological mechanism of SEPT14 mutation-induced sperm head defects. To identify SEPT14 interactors, co-immunoprecipitation (co-IP) and nano-liquid chromatography-mass spectrometry/mass spectrometry were applied. Immunostaining showed that SEPT14 was significantly localized to the manchette structure. The SEPT14 interactors were identified and classified as (1) SEPT-, (2) microtubule-, (3) actin-, and (4) sperm structure-related proteins. One interactor, ACTN4, an actin-holding protein, was selected for further study. Co-IP experiments showed that SEPT14 interacts with ACTN4 in a male germ cell line. SEPT14 also co-localized with ACTN4 in the perinuclear and manchette regions of the sperm head in early elongating spermatids. In the cell model, mutated SEPT14 disturbed the localization pattern of ACTN4. In a clinical aspect, sperm with mutant SEPT14, SEPT14A123T (p.Ala123Thr), and SEPT14I333T (p.Ile333Thr), have mislocalized and fragmented ACTN4 signals. Sperm head defects in donors with SEPT14 mutations are caused by disruption of the functions of ACTN4 and actin during sperm head formation.

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.