Enzymatic Preparation, In-Depth Molecular Analysis, and In Vitro Digestion Simulation of Palmitoleic Acid (ω-7)-Enriched Fish Oil Triacylglycerols.

In this study, an enzymatic reaction was developed for synthesizing pure triacylglycerols (TAG) with a high content of palmitoleic acid (POA) using fish byproduct oil. The characteristics of synthesized structural TAGs rich in POA (POA-TAG) were analyzed in detail through ultrahigh-performance liquid chromatography Q Exactive orbitrap mass spectrometry. Optimal conditions were thoroughly investigated and determined for reaction systems, including the use of Lipozyme TL IM and Novozym 435, 15 wt % lipase loading, substrate mass ratio of 1:3, and water content of 2.5 and 0.5 wt %, respectively, resulting in yields of 67.50 and 67.45% for POA-TAG, respectively. Multivariate statistical analysis revealed that TAG 16:1/16:1/20:4, TAG 16:1/16:1/16:1, TAG 16:1/16:1/18:1, and TAG 16:0/16:1/18:1 were the main variables in Lipozyme TL IM and Novozym 435 enzyme-catalyzed products under different water content conditions. Finally, the fate of POA-TAG across the gastrointestinal tract was simulated using an in vitro digestion model. The results showed that the maximum release of free fatty acids and apparent rate constants were 71.44% and 0.0347 s-1, respectively, for POA-TAG lipids, and the physical and structural characteristics during digestion depended on their microenvironments. These findings provide a theoretical basis for studying the rational design of POA-structural lipids and exploring the nutritional and functional benefits of POA products.

Correction: Teng et al. Efficacy Assessment of Phage Therapy in Treating Staphylococcus aureus-Induced Mastitis in Mice. Viruses 2022, 14, 620.

In the original publication [...].

Baseline immune status and the effectiveness of response to enteral nutrition among ICU patients with COVID-19: An observational, retrospective study.

OBJECTIVES: This study aimed to compare how immunocompromised and immunocompetent patients responded differently to enteral nutrition (EN) support in intensive care units (ICUs) during the COVID-19 pandemic, including serum nutritional biomarkers, inflammatory biomarkers, gastrointestinal (GI) intolerance symptoms, and clinical outcomes. METHODS: An observational, retrospective study was conducted in the ICUs of a teaching hospital in southwest China. We recruited a convenience sample of 154 patients between December 2022 and February 2023. We defined immunocompromise as primary immunodeficiency diseases, active malignancy, receiving cancer chemotherapy, HIV infection, solid organ transplantation, hematopoietic stem cell transplantation, receiving corticosteroid therapy with a target dose, receiving biological immune modulators, or receiving disease-modifying antirheumatic drugs or other immunosuppressive drugs. We conducted a Mann-Whitney U test, χ2 test, or generalized estimation equation model to explore the differences between immunocompromised and immunocompetent patients. RESULTS: Among the 154 study participants, 41 (27%) were defined as immunocompromised. The immunocompromised patients were younger than the immunocompetent patients. There were no statistically significant differences between the two groups with respect to serum nutritional biomarkers, inflammatory biomarkers, incidence of GI intolerance symptoms, and in-hospital mortality. However, the immunocompromised patients exhibited a longer hospitalization duration than the immunocompetent patients. CONCLUSION: We found that the immunocompromised patients spent more time in the hospital. These findings may help us to standardize the participants before EN interventional studies better and better individualize EN supports based on patients' immunity status.

Assessing immunogenicity of CRISPR-NCas9 engineered strain against porcine epidemic diarrhea virus.

Porcine epidemic diarrhea (PED) caused by porcine epidemic diarrhea virus (PEDV), is an acute and highly infectious disease, resulting in substantial economic losses in the pig industry. Given that PEDV primarily infects the mucosal surfaces of the intestinal tract, it is crucial to improve the mucosal immunity to prevent viral invasion. Lactic acid bacteria (LAB) oral vaccines offer unique advantages and potential applications in combatting mucosal infectious diseases, making them an ideal approach for controlling PED outbreaks. However, traditional LAB oral vaccines use plasmids for exogenous protein expression and antibiotic genes as selection markers. Antibiotic genes can be diffused through transposition, transfer, or homologous recombination, resulting in the generation of drug-resistant strains. To overcome these issues, genome-editing technology has been developed to achieve gene expression in LAB genomes. In this study, we used the CRISPR-NCas9 system to integrate the PEDV S1 gene into the genome of alanine racemase-deficient Lactobacillus paracasei △Alr HLJ-27 (L. paracasei △Alr HLJ-27) at the thymidylate synthase (thyA) site, generating a strain, S1/△Alr HLJ-27. We conducted immunization assays in mice and piglets to evaluate the level of immune response and evaluated its protective effect against PEDV through challenge tests in piglets. Oral administration of the strain S1/△Alr HLJ-27 in mice and piglets elicited mucosal, humoral, and cellular immune responses. The strain also exhibited a certain level of resistance against PEDV infection in piglets. These results demonstrate the potential of S1/△Alr HLJ-27 as an oral vaccine candidate for PEDV control. KEY POINTS: • A strain S1/△Alr HLJ-27 was constructed as the candidate for an oral vaccine. • Immunogenicity response and challenge test was carried out to analyze the ability of the strain. • The strain S1/△Alr HLJ-27 could provide protection for piglets to a certain extent.

Rapid and sensitive lateral flow biosensor for the detection of GII human norovirus based on immunofluorescent nanomagnetic microspheres.

Human norovirus (HuNoV) is the most predominant viral agents of acute gastroenteritis. Point-of-care testing (POCT) based on lateral flow immunochromatography (LIFC) has become an important tool for rapid diagnosis of HuNoVs. However, low sensitivity and lack of quantitation are the bottlenecks of traditional LIFC. Thus, we established a rapid and accurate technique that combined immunomagnetic enrichment (IM) with LFIC to identify GII HuNoVs in fecal specimens. Before preparing immunofluorescent nanomagnetic microspheres and achieving the effect of HuNoV enrichment in IM and fluorescent signal in LFIC, amino-functionalized magnetic beads (MBs) and carboxylated quantum dots (QDs) were coupled at a mass ratio of 4:10. Anti-HuNoV monoclonal antibody was then conjugated with QDs-MB. The limit of detection was 1.56 × 104 copies/mL, and the quantitative detection range was 1.56 × 104 copies/mL-1 × 106 copies/mL under optimal circumstances. The common HuNoV genotypes GII.2, GII.3, GII.4, and GII.17 can be detected, there was no cross-reaction with various enteric viruses, including rotavirus, astrovirus, enterovirus, and sapovirus. A comparison between IM-LFIC and RT-qPCR for the detection of 87 fecal specimens showed a high level of agreement (kappa = 0.799). This suggested that the method is rapid and sensitive, making it a promising option for point-of-care testing in the future.

Association with the plasma atherogenic index with hepatic steatosis and fibrosis in the US population.

Plasma atherogenic index (AIP) reflects a novel intricate biochemical indicator of lipids' metabolism. The involvement of lipid metabolism for pathogenesis concerning nonalcoholic fatty liver disease (NAFLD) has been established. However, the precise association across AIP and hepatic steatosis and fibrosis remains unclear. This present investigation explored the potential correlation across AIP, hepatic steatosis and fibrosis. Data were acquired through National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. Hepatic steatosis was detected through the controlled attenuation parameter (CAP), while hepatic fibrosis was examined via liver stiffness measurement (LSM). The study employed multiple linear, Fitted smoothed curves and subgroup analyses were used for investigating relationships between the AIP, CAP, and LSM. The study recruited 6239 participants. In multivariate linear regression analysis, findings indicated a remarkable correlation between AIP and exacerbated NAFLD risk [odds ratio (95% confidence interval), 1.17 (1.12, 1.21)]. Analysis further revealed a positive link across AIP and hepatic steatosis, as indicated through the CAP [ß (95% CI), 4.07 (3.32, 4.82)]. Tests for non-linearity, revealed a non-linear correlation between AIP and CAP (inflection point = 0.22). Subgroup analyses assessed the consistency of the link across AIP and CAP, indicating that the association remained comparable across all subgroups. Following the adjustment for all relevant variables, the linear regression analysis revealed a lack of statistical significance across the AIP and hepatic fibrosis. [LSM, ß (95% CI), -0.39 (-1.06, 0.28), P = .2501]. Smooth-fitting curves examined the link across AIP and LSM and showed a U-shaped pattern, indicating their positive correlation with AIP less than 0.48. However, no significant correlation was observed with AIP more than 0.48. This study highlighted a substantial positive relationship across AIP and hepatic steatosis, as measured through CAP, and suggests that it may be used as an efficient and rapid measure for clinical prediction of hepatic steatosis.

A systematic review and meta-analysis indicates a high risk of human noroviruses contamination in vegetable worldwide, with GI being the predominant genogroup.

Human noroviruses (HuNoVs) are the most predominant viral agents of acute gastroenteritis. Vegetables are important vehicles of HuNoVs transmission. This study aimed to assess the HuNoVs prevalence in vegetables. We searched the Web of Science, Excerpta Medica Database, PubMed, and Cochrane databases until June 1, 2023. A total of 27 studies were included for the meta-analysis. Statistical analysis was conducted using Stata 14.0 software. This analysis showed that the pooled HuNoVs prevalence in vegetables was 7 % (95 % confidence interval (CI): 3-13) worldwide. The continent with largest number of studies was Europe, and the highest number of samples was lettuce. As revealed by the results of the subgroup meta-analysis, the prevalence of GI genogroup was the highest (3 %, 95 % CI: 1-7). A higher prevalence was seen in vegetables from farms (18 %, 95 % CI: 5-37), while only 4 % (95 % CI: 1-8) in retail. The HuNoVs prevalence of ready-to-eat vegetables and non-ready-to-eat vegetables was 2 % (95 % CI: 0-8) and 9 % (95 % CI: 3-16), respectively. The prevalence by quantitative real time RT-PCR was 8 % (95 % CI: 3-15) compared to 3 % (95 % CI: 0-13) by conventional RT-PCR. Furthermore, the HuNoVs prevalence in vegetables was 6 % (95 % CI: 1-14) in ISO pretreatment method and 8 % (95 % CI: 1-19) in non-ISO method, respectively. This study is helpful in comprehensively understanding the prevalence of HuNoVs contamination in vegetables worldwide.

The HSP90-MYC-CDK9 network drives therapeutic resistance in mantle cell lymphoma.

Brexucabtagene autoleucel CAR-T therapy is highly efficacious in overcoming resistance to Bruton's tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma. However, many patients relapse post CAR-T therapy with dismal outcomes. To dissect the underlying mechanisms of sequential resistance to BTKi and CAR-T therapy, we performed single-cell RNA sequencing analysis for 66 samples from 25 patients treated with BTKi and/or CAR-T therapy and conducted in-depth bioinformatics™ analysis. Our analysis revealed that MYC activity progressively increased with sequential resistance. HSP90AB1 (Heat shock protein 90 alpha family class B member 1), a MYC target, was identified as early driver of CAR-T resistance. CDK9 (Cyclin-dependent kinase 9), another MYC target, was significantly upregulated in Dual-R samples. Both HSP90AB1 and CDK9 expression were correlated with MYC activity levels. Pharmaceutical co-targeting of HSP90 and CDK9 synergistically diminished MYC activity, leading to potent anti-MCL activity. Collectively, our study revealed that HSP90-MYC-CDK9 network is the primary driving force of therapeutic resistance.

Distribution and release of PFAS from AFFF-impacted asphalt: How does it compare to concrete?

Aqueous film forming foam (AFFF)-impacted asphalt and concrete may serve as potential secondary sources of per- and polyfluoroalkyl substances (PFAS) to the environment through surficial leaching. We aimed to understand the vertical distribution and surficial release of PFAS from AFFF-impacted asphalt and concrete cores collected from various locations (∼10-70 m distance between samples). Among the PFAS analyzed, 6:2 FTS was observed as having the highest concentration in the surface layer (0 - 0.5 cm) of concrete (225 µg kg-1) and in the runoff from the concrete (2600 ng L-1). PFOS was detected at the highest concentration in the surface layer (0 - 0.5 cm) of asphalt (47 µg kg-1) and associated runoff (780 ng L-1). The total mass of PFAS released during three rainfall simulations accounts for a fraction of the total mass in the surface layer (0 - 0.5 cm), ranging from 0.10 - 9.8% and 0.078 - 2.4% for asphalt and concrete cores, respectively. Asphalt exhibited a higher release rate than concrete, demonstrated by the higher total release coefficient of PFAS (4 - 16 m-2) compared to that of concrete cores (1 - 5 m-2). These results suggested that, similar to concrete, AFFF-impacted asphalt may be a secondary source of PFAS to the environment.

Enhancer of Zeste Homolog 2 Inhibitor SHR2554 in Relapsed or Refractory Peripheral T-cell Lymphoma: Data from the First-in-Human Phase I Study.

PURPOSE: Patients with peripheral T-cell lymphomas (PTCL) in the relapsed or refractory (r/r) setting have only a limited number of therapies available, and the prognosis is extremely poor. SHR2554 is an oral inhibitor against EZH2, a rational therapeutic target for lymphomas. PATIENTS AND METHODS: This was a multicenter, two-part, phase I study of SHR2554 in r/r mature lymphoid neoplasms. In part I, 350 mg twice daily was established as the recommended phase II dose (RP2D) based on the findings during dose escalation and expansion; subsequently, selected lymphoma subtypes were recruited in clinical expansion cohorts to receive SHR2554 at RP2D. Here, we provide an in-depth assessment of SHR2554 at RP2D in subpopulation with r/r PTCL. RESULTS: Twenty-eight patients were included for analysis (17 angioimmunoblastic T-cell lymphoma and 11 not otherwise specified). Eighteen (64%) patients had received ≥2 lines of previous anticancer therapies. The objective response rate was 61% [95% confidence interval (CI), 41-78]. Responses were still ongoing in 59% (10/17) of the responders; estimated median duration of response was 12.3 months (95% CI, 7.4-not reached). Median progression-free survival was 11.1 months (95% CI, 5.3-22.0), and 12-month overall survival rate was 92% (95% CI, 72-98). The most common grade 3 or 4 treatment-related adverse events were decreased platelet count [nine (32%)] as well as decreased white blood cell count, decreased neutrophil count, and anemia [four (14%) for each]. No treatment-related deaths were reported. CONCLUSIONS: This extended follow-up analysis further supports SHR2554 as a therapeutic opportunity for patients with r/r PTCL.

High-Throughput Screening of pH-Dependent ß-sheet Self-Assembling Peptide.

pH-dependent peptide biomaterials hold tremendous potential for cell delivery and tissue engineering. However, identification of responsive self-assembling sequences with specified secondary structure remains a challenge. In this work, An experimental procedure based on the one-bead one-compound (OBOC) combinatorial library is developed to rapidly screen self-assembling ß-sheet peptides at neutral aqueous solution (pH 7.5) and disassemble at weak acidic condition (pH 6.5). Using the hydrophobic fluorescent molecule thioflavin T (ThT) as a probe, resin beads displaying self-assembling peptides show fluorescence under pH 7.5 due to the insertion of ThT into the hydrophobic domain, and are further cultured in pH 6.5 solution. The beads with extinguished fluorescence are selected. Three heptapeptides are identified that can self-assemble into nanofibers or nanoparticles at pH 7.5 and disassemble at pH 6.5. P1 (LVEFRHY) shows a rapid acid response and morphology transformation with pH modulation. Changes in the charges of histidine and hydrophobic phenyl motif of phenylalanine may play important roles in the formation of pH-responsive ß-sheet nanofiber. This high-throughput screening method provides an efficient way to identify pH-dependent ß-sheet self-assembling peptide and gain insights into structural design of such nanomaterials.

Porcine epidemic diarrhea virus strain CH/HLJ/18 isolated in China: characterization and phylogenetic analysis.

BACKGROUND: Porcine epidemic diarrhea (PED) is an infectious disease of the digestive tract caused by the porcine epidemic diarrhea virus (PEDV), characterized by vomiting, severe diarrhea, and high mortality rates in piglets. In recent years, the distribution of this disease in China has remarkably increased, and its pathogenicity has also increased. PEDV has been identified as the main cause of viral diarrhea in piglets. This study aimed to understand the genetic evolution and diversity of PEDV to provide a theoretical basis for the development of new vaccines and the prevention and treatment of PED. METHODS: A PEDV strain was isolated from the small intestine of a diarrheal piglet using Vero cells. The virus was identified using reverse transcription-polymerase chain reaction (RT-PCR), indirect immunofluorescence assay (IFA), and transmission electron microscopy. The whole genome sequence was sequenced, phylogenetic analysis was conducted using MEGA (version 7.0), and recombination analysis was performed using RDP4 and SimPlot. The S protein amino acid sequence was aligned using Cluster X (version 2.0), and the S protein was modeled using SWISS-MODEL to compare differences in structure and antigenicity. Finally, the piglets were inoculated with PEDV to evaluate its pathogenicity in newborn piglets. RESULT: PEDV strain CH/HLJ/18 was isolated. CH/HLJ/18 shared 89.4-99.2% homology with 52 reference strains of PEDV belonging to the GII-a subgroup. It was a recombinant strain of PEDV BJ-2011-1 and PEDV CH_hubei_2016 with a breakpoint located in ORF1b. Unique amino acid deletions and mutations were observed in the CH/HLJ/18 S protein. The piglets then developed severe watery diarrhea and died within 7 d of inoculation with CH/HLJ/18, suggesting that CH/HLJ/18 was highly pathogenic to newborn piglets. CONCLUSION: A highly pathogenic recombinant PEDV GII-a strain, CH/HLJ/18, was identified in China, with unique deletion and mutation of amino acids in the S protein that may lead to changes in protein structure and antigenicity. These results will be crucial for understanding the prevalence and variation of PEDV and for preventing and controlling PED.

Correlates of the Veterans Visiting Emergency Departments in Taiwan: A Comparison Before and After the Coronavirus Disease 2019 Pandemic.

BACKGROUND: Taiwan has a substantial number of veterans, but knowledge regarding their emergency department (ED) visits during the coronavirus disease 2019 (COVID-19) pandemic remains limited. This study examined the characteristics of veterans' ED visits during Taiwan's COVID-19 epidemic. METHODS: This was a cross-sectional study conducted at the ED of a large veteran medical center located in Taipei, Taiwan, from May 2018 to October 2021. We analyzed the numbers and features of visits in summer and autumn according to the first wave of the COVID-19 epidemic in Taiwan in 2021. RESULTS: Medical institutions were positively associated with veteran status. Emergency department complaints of trauma (adjusted odds ratio [AOR] = 1.15, 95% CI: 1.06-1.25; summer P < .01) and chest pain/tightness (AOR = 1.65, 95% CI: 1.45-1.87; summer P < .01; AOR = 1.4, 95% CI: 1.26-1.55; P < .01) were associated with increased odds of being a veteran. Triage levels above 2 were positively associated with veteran status in the autumn model (AOR = 1.14, 95% CI: 1.07-1.22; P < .01). Patients hospitalized after ED visits were associated with reduced odds of veteran status (P < .01). Those who spent a long time in the ED were more likely to be veterans than those who spent a shorter time in the ED (P < .01). Veterans were less likely to visit the ED regardless of the time frame of the study period (P < .01), except during the COVID-19 outbreak in the autumn (2019-2020). CONCLUSIONS: The distinctions in ED visits highlighted the individuality of veterans' medical needs. Our findings suggest that the veteran medical system can add to the focus on improving senior-friendly care, fall prevention, quality of life of institutionalized veterans, access for homeless veterans, and care for ambulatory care-sensitive conditions.

Biodegradation of benzo[a]pyrene by a marine Chlorella vulgaris LH-1 with heterotrophic ability.

In this study, a microalga, Chlorella vulgaris LH-1, with heterotrophic ability to degrade BaP was explored. The effect of BaP concentration on microalga growth was investigated, and the possible biodegradation mechanism of BaP was proposed. Results showed that low BaP concentration (<5 mg/L) had less negative influence on the growth of this microalga under mixotrophic condition, but high BaP concentration (>5 mg/L) had a significant inhibitory effect on its growth. During heterotrophic cultivation, low BaP concentration (<20 mg/L) promoted the growth of C. vulgaris LH-1, whereas high BaP concentration (>20 mg/L) inhibited its growth significantly. The degradation rates of mixotrophic and heterotrophic C. vulgaris LH-1 were 62.56 %-74.13 % and 52.07 %-71.67 %, respectively, when the BaP concentration ranged from 0.5 mg/L to 2 mg/L. The expression of functional enzyme genes of C. vulgaris LH-1 such as phenol 2-monooxygenase activity, protocatechuate 3,4-dioxygenase activity, catechol 1,2-dioxygenase activity, styrene degradation, and benzoate degradation were upregulated in the process of BaP degradation. C. vulgaris LH-1 may degrade BaP by monooxygenase and dioxygenase simultaneously. The degradation of BaP by this microalga under mixotrophic condition goes through the degradation pathway of phthalic acid, whereas it goes through the degradation pathway of benzoic acid under heterotrophic condition.

Effect of thickened water swallow training in tube-feeding and dysphagia patients in the acute and early subacute phases of stroke: A quasi-experimental study.

BACKGROUND: Thickened water has been widely used in patients with dysphagia who receive oral feeding, but there is little evidence for tube-feeding patients. OBJECTIVE: To explore the effects of thickened water swallow training in tube-feeding and dysphagia patients in the acute and early subacute phases of stroke. METHODS: A quasi-experimental study. Hospitalised patients with acute and early subacute stroke who received tube feeding due to dysphagia were recruited from March to December 2021. Patients assigned to the intervention group (n = 23) received thickened water swallow training three times daily until the feeding tube was removed or they were discharged, and patients in the control group (n = 23) received usual care. The main outcomes were duration of tube feeding and rates of weaning at discharge. RESULTS: Patients in the intervention group had a shorter tube-feeding duration (p = .046) and a higher rate of weaning at discharge (p = .017) than those in the control group. Significant interaction effects between time and group were detected regarding quality of life except for the swallowing burden dimension. CONCLUSIONS: Thickened water swallow training is feasible and effective for stroke patients with tube feeding and can shorten the duration of tube feeding and improve the rates of weaning and quality of life. Healthcare providers in nonrehabilitation units should actively conduct swallowing function intervention training to maximise the potential for acute and early subacute phase rehabilitation.

Down syndrome child with multiple heart diseases: A case report.

BACKGROUND: Down syndrome, also known as trisomy 21 syndrome, is commonly associated with congenital heart disease, and can often result in early formation of pulmonary hypertension. The development of pulmonary hypertension can result from factors such as intracardiac and macrovascular shunts, and upper airway obstruction or hypoplasia of lung tissue. Individuals with Down syndrome and congenital heart disease have a significantly lower average life expectancy, with surgical intervention being the most viable treatment option to improve longevity. CASE SUMMARY: We report the case of a 13-year-old boy with Down syndrome presenting with atrial septal defect and patent ductus arteriosus along with severe pulmonary hypertension. The electrocardiogram shows sinus rhythm and right ventricular hypertrophy. The echocardiogram shows an atrial septal defect with interrupted echo in the interatrial septum, measuring 0.813 cm in length. The patient was initially refused to be offered surgical treatment by many hospitals due to the high surgical risk and pulmonary artery resistance. After discussing the patient's diagnosis and treatment options, we ultimately recommended surgical treatment. However, the patient and their family declined this recommendation and chose to be discharged. During the follow-up period of 6 mo, there were no significant improvements or deteriorations in the patient's condition. CONCLUSION: In conclusion, this case highlights the challenges faced by individuals with Down syndrome and congenital heart disease complicated by severe pulmonary hypertension. Timely intervention and a multidisciplinary approach are crucial for improving prognosis and life expectancy. Further research is needed to enhance our understanding and develop effective interventions for this population.

Spinal cord injury: global burden from 1990 to 2019 and projections up to 2030 using Bayesian age-period-cohort analysis.

Background: Spinal cord injuries, often resulting from spine fractures, can lead to severe lifelong symptoms such as paraplegia and even mortality. Over the past few decades, there has been a concerning increase in the annual incidence and mortality rates of spinal cord injuries, which has also placed a growing financial strain on healthcare systems. This review aims to offer a comprehensive overview of spinal cord injuries by estimating their global incidence, prevalence, and the impact in terms of years lived with disability, using data obtained from the 2019 Global Burden of Disease Study. Method: In this study, we utilized data from the 2019 Global Burden of Disease Study, a widely recognized source for global health data. Our methodology involved estimating the global incidence and prevalence of spinal cord injuries while also assessing the impact on years lived with a disability. We analyzed this data comprehensively to identify patterns and trends and made predictions. Finding: This research delved into the evolving trends in the global burden of spinal cord injuries, identified key risk factors, and examined variations in incidence and disability across different Socio-demographic Index (SDI) levels and age groups. Briefly, in 2019, the global incidence and burden of YLDs of SCI significantly increased compared to 1990. While males had higher incidence rates compared to females. Falls were identified as the primary cause of SCI. Trend projections up to 2030 revealed a slight decrease in ASIR for males, an upward trend in age-specific incidence rates for both sexes and a similar pattern in age-standardized YLD rates. Additionally, our findings provided crucial groundwork for shaping future policies and healthcare initiatives, with the goal of mitigating the burden of spinal cord injuries, enhancing patient outcomes, and fortifying prevention efforts. Interpretation: Understanding the global burden of spinal cord injuries is essential for designing effective healthcare policies and prevention strategies. With the alarming increase in prevalence rates and their significant impact on individuals and healthcare systems, this research contributes vital insights to guide future efforts in reducing the incidence of spinal cord injuries, improving the quality of life for affected individuals, and reducing the economic burden on healthcare systems worldwide.

Potentiation of apoptosis in drug-resistant mantle cell lymphoma cells by MCL-1 inhibitor involves downregulation of inhibitor of apoptosis proteins.

Bruton's tyrosine kinase inhibitors (BTKi) and CAR T-cell therapy have demonstrated tremendous clinical benefits in mantle cell lymphoma (MCL) patients, but intrinsic or acquired resistance inevitably develops. In this study, we assessed the efficacy of the highly potent and selective MCL-1 inhibitor AZD5991 in various therapy-resistant MCL cell models. AZD5991 markedly induced apoptosis in these cells. In addition to liberating BAK from the antiapoptotic MCL-1/BAK complex for the subsequent apoptosis cascade, AZD5991 downregulated inhibitor of apoptosis proteins (IAPs) through a BAK-dependent mechanism to amplify the apoptotic signal. The combination of AZD5991 with venetoclax enhanced apoptosis and reduced mitochondrial oxygen consumption capacity in MCL cell lines irrespective of their BTKi or venetoclax sensitivity. This combination also dramatically inhibited tumor growth and prolonged mouse survival in two aggressive MCL patient-derived xenograft models. Mechanistically, the augmented cell lethality was accompanied by the synergistic suppression of IAPs. Supporting this notion, the IAP antagonist BV6 induced dramatic apoptosis in resistant MCL cells and sensitized the resistant MCL cells to venetoclax. Our study uncovered another unique route for MCL-1 inhibitor to trigger apoptosis, implying that the pro-apoptotic combination of IAP antagonists and apoptosis inducers could be further exploited for MCL patients with multiple therapeutic resistance.

Gender- and age-specific associations between psychosocial work conditions and perceived work sustainability in the general working population in Taiwan.

OBJECTIVES: One aspect of work sustainability pertains to workers' intention to remain in their current job until reaching retirement age. Various adverse working conditions are expected to diminish work sustainability among different social groups. This study aims to examine these associations across gender and age groups. METHODS: The study participants were 19,152 economically-active adults in a national survey conducted in Taiwan. Information concerning psychosocial working conditions were obtained through interviews, using the Job Content Questionnaire. Work sustainability was evaluated by one question that asked whether the participants felt they would be able to do their current job until the age of 60. The association between psychosocial work conditions and work sustainability was examined by logistic regression analysis. We further performed stratified analysis to explore age and gender-specific associations. RESULTS: We observed that 14.2% and 17.1% of male and female workers reported low work sustainability. Workers in the electronics industries and female workers in the healthcare and education sectors reported low work sustainability. Gender-specific analyses showed that low job control among men and shift work among women were significantly associated with low work sustainability. Age-specific analyses indicated that having poor health, shift work, and long working hours in younger workers, and having low job control in older workers were associated with low work sustainability. CONCLUSION: To retain older workers in the labor market, policies should aim at the improvement of psychosocial work conditions, and gender- and age-specific issues should be taken into consideration.

LILAR, a novel long noncoding RNA regulating autophagy in the liver tissues of endotoxemic mice through a competing endogenous RNA mechanism.

Sepsis is an often-deadly complication of infection that can lead to multiple organ failure. Previous studies have demonstrated that autophagy has a protective effect on liver injury in sepsis. Here, we report a novel long noncoding RNA (lncRNA), named lipopolysaccharide (LPS)-induced liver autophagy regulator (LILAR), which was highly induced in the liver tissues of endotoxemic mice. LILAR deficiency significantly increased the susceptibility of mice to LPS. In contrast, LILAR overexpression rescued the liver injury mediated by LILAR deficiency and increased the survival of LILAR knockout mice with endotoxemia. Autophagy-related protein 13 (Atg13) is a potential downstream target gene of LILAR. LILAR deficiency notably decreased Atg13 expression and suppressed autophagy in the livers of mice challenged with LPS. A reporter gene assay showed that LILAR competitively adsorbed miR-705 to increase the expression of Atg13 in cultured cells, indicating that LILAR participates in the regulation of the autophagy in the liver tissues of endotoxemic mice through a competitive endogenous RNA mechanism. In summary, we identified a novel lncRNA, LILAR, as a hepatic autophagy regulator, which not only promotes our understanding of liver pathophysiology but also provides a potential therapeutic target and/or diagnostic biomarker for liver injury in endotoxemia.