Transcriptional, post-transcriptional, and post-translational regulation of polyunsaturated fatty acid synthase genes in Aurantiochytrium limacinum strain BL10: Responses to nitrogen starvation.

Under nitrogen deficient conditions, the Aurantiochytrium limacinum strain BL10 greatly increases the production of docosahexaenoic acid (DHA) and n-6 docosapentaenoic acid. Researchers have yet to elucidate the mechanism by which BL10 promotes the activity of polyunsaturated fatty acid synthase (Pfa), which plays a key role in the synthesis of polyunsaturated fatty acid (PUFA). Analysis in the current study revealed that in nitrogen-depleted environments, BL10 boosts the transcription and synthesis of proteins by facilitating the expression of pfa genes via transcriptional regulation. It was also determined that BL10 adjusts the lengths of the 5'- and 3'-untranslated regions (suggesting post-transcriptional regulation) and modifies the ratio of two Pfa1 isoforms to favor PUFA production via post-translational regulation (ubiquitination). These findings clarify the exceptional DHA production of BL10 and provide additional insights into the regulatory mechanisms of PUFA biosynthesis in Aurantiochytrium.

Immune-Mediated Necrotizing Myopathy Associated With Anti-signal Recognition Particle Antibody Complicated With Acute Respiratory Distress Syndrome: A Report of Two Cases.

Immune-mediated necrotizing myopathy (IMNM) represents a rare category of inflammatory myopathies characterized by more severe and rapid progression of symmetrical proximal muscle weakness. It is also marked by notably elevated serum muscle enzyme levels and distinct histological features, setting it apart from other types of myositis. Moreover, acute chronic lung respiratory dysfunction is a major comorbidity of great concern. We herein present two cases of IMNM associated with anti-signal recognition particle antibodies complicated by acute respiratory distress syndrome.

Canadian Gender-Based Violence Prevention Programs: Gaps and Opportunities.

Gender-based violence (GBV) prevention programs have long played an important part in both teaching the realities of GBV and training people in techniques to avert, mitigate, and respond to violence. This article examines the current state of GBV prevention training in Canada through an analysis of 81 GBV education programs provided by antiviolence organizations and universities. We identified notable gaps in topics relating to technology-facilitated violence and abuse in programs targeting men and in the provision of bystander intervention training. Each of these areas represents important, but as yet unrealized, opportunities in violence prevention.

Low Vitamin D Concentration Is Associated with Increased Depression Risk in Adults 20-44 Years Old, an NHANES 2007-2018 Data Analysis with a Focus on Perinatal and Breastfeeding Status.

The objective was to investigate associations of serum vitamin D concentration with depressive symptoms and assess the impact that vitamin D concentration has on the occurrence of depressive symptoms in 20-44-year-old pregnant women, postpartum women, non-pp women (non-pregnant/postpartum women), and men, including a separate subgroup analysis of postpartum breastfeeding and non-breastfeeding women. The study populations were selected from the 2007-2018 NHANES public data. Subjective interview data and objective laboratory data including depressive symptoms, serum vitamin D concentration, nutrient intake, and demographic information were utilized. Two diet patterns were created using principal component analysis, and a Bayesian multinomial model was fit to predict the depression outcomes for each subpopulation. The estimates for the log vitamin D slope parameter were negative for all cohorts; as vitamin D increased, the probability of having no depression increased, while the probability of depression decreased. The pregnant cohort had the steepest vitamin D slope, followed by postpartum women, then non-pp women and men. Higher vitamin D concentration had more impact on decreasing depression risk in pregnant and postpartum women compared to non-pp women and men. Among postpartum women, higher vitamin D concentration had a greater influence on decreasing breastfeeding women's depression risk than non-breastfeeding women.

AM-DMF-SCP: Integrated Single-Cell Proteomics Analysis on an Active Matrix Digital Microfluidic Chip.

Single-cell proteomics offers unparalleled insights into cellular diversity and molecular mechanisms, enabling a deeper understanding of complex biological processes at the individual cell level. Here, we develop an integrated sample processing on an active-matrix digital microfluidic chip for single-cell proteomics (AM-DMF-SCP). Employing the AM-DMF-SCP approach and data-independent acquisition (DIA), we identify an average of 2258 protein groups in single HeLa cells within 15 min of the liquid chromatography gradient. We performed comparative analyses of three tumor cell lines: HeLa, A549, and HepG2, and machine learning was utilized to identify the unique features of these cell lines. Applying the AM-DMF-SCP to characterize the proteomes of a third-generation EGFR inhibitor, ASK120067-resistant cells (67R) and their parental NCI-H1975 cells, we observed a potential correlation between elevated VIM expression and 67R resistance, which is consistent with the findings from bulk sample analyses. These results suggest that AM-DMF-SCP is an automated, robust, and sensitive platform for single-cell proteomics and demonstrate the potential for providing valuable insights into cellular mechanisms.

Sex Differences in Outcomes after Endovascular Thrombectomy for Patients with Acute Ischemic Stroke.

INTRODUCTION: Endovascular thrombectomy (EVT) is the standard of care for patients with large-vessel occlusion acute ischemic stroke (AIS). There may be differing recanalization effectiveness based on patients' sex, and understanding such variations can improve patient outcomes by adjusting for differences. We aimed to assess the sex differences in outcome after EVT for patients with AIS. METHODS: We retrospectively analyzed 250 consecutive AIS patients who underwent EVT from July 2019 to February 2022 across two large comprehensive tertiary care stroke centers in China. Outcomes of male patients were compared to females, where poor outcome was defined as a modified Rankin score (mRS) of 3-6 at 90 days. RESULTS: Male patients had higher rates of symptomatic intracranial hemorrhage (sICH) (12.50% vs. 4.05%, p = 0.042) and higher hospitalization costs (114,541.08 vs. 105,790.27 RMB, p = 0.024). Male patients also had a longer median onset-to-needle time (ONT) (146.00 [104.00, 202.00] versus 120.00 [99.25, 144.75], p = 0.026). However, there were no differences in hospitalization length (p = 0.251), 90-day favorable outcome (p = 0.952), and 90-day mortality (p = 0.931) between the sexes. CONCLUSION: Female patients had lower hospitalization costs and sICH rates than males after EVT for AIS. Identifying such differences and implementing measures, including adaptations to workflow optimization, would help to reduce the ONT and last known normal-to-puncture time seen in males to improve patient outcomes. Despite such variations, favorable outcomes and mortality are similar in female and male AIS patients.

A high-performance organic thin-film transistor with Parylene/PMMA bilayer insulation based on P3HT.

This work introduces a pioneering approach in the development of organic thin-film transistors (OTFTs), featuring a double-layer dielectric structure that combines poly(para-xylylene)s (Parylene) and poly(methyl methacrylate) (PMMA) to leverage the high insulation properties and high surface polarity of Parylene with the low insulation properties and low surface polarity of PMMA. This combination results in devices that showcase significantly enhanced electrical performance, including superior charge carrier mobility, increased current on/off ratios, and greater transconductance. Utilizing poly(3-hexylthiophene) (P3HT) for the active layer, the study demonstrates the advantage of the dual dielectric layers in minimizing hysteresis in the transfer curve, thereby facilitating the systematic growth of the organic active layer and enhancing electrical conductivity over single-layer alternatives. The superior performance of the Parylene/PMMA double-layer insulating structure opens new avenues for the advancement of organic electronics, presenting methodologies for performance optimization and expanding the application spectrum of OTFTs.

Erratum: [Corrigendum] Aloperine activates the Nrf2­ARE pathway when ameliorating early brain injury in a subarachnoid hemorrhage model.

[This corrects the article DOI: 10.3892/etm.2018.5896.].

Metagenomic next-generation sequencing assistance in identifying Mycobacterium avium meningoencephalitis: A case report and literature review.

Nontuberculous mycobacteria associated intracranial infection is a rare disease that mainly occurs in HIV-infected patients. The disease has a poor prognosis. The authors report a case of non-tuberculous mycobacterial meningoencephalitis in a non-AIDS patient, but long history of poorly controlled type 2 diabetes mellitus. A 55-year-old, right-handed, male patient presented with an 8-day history of fever, episodes of severe headache with signs of meningeal irritation. MRI showed hyperintensities/contrast enhancement in the visual pathways, basal ganglia sellar region and leptomeninges. No etiological diagnosis was reached until metagenomic next-generation sequencing (mNGS) was used, showing the presence of Mycobacterium avium. The patient was cured with aggressive antimycobacterial therapy. The authors discuss the clinical manifestations and drug therapy of nontuberculous mycobacteria-related intracranial infections by reviewing relevant literature. As meningoencephalitis by Mycobacterium avium has a high mortality an early diagnosis and appropriate therapeutic interventions are warranted. For this reason, the use of mNGS can be helpful to avoid therapeutic delay.

IgLON5 autoimmunity in a patient with Creutzfeldt-Jakob disease: case report and review of literature.

Objective: We present the case of a patient with clinical and imaging features of sporadic Creutzfeldt-Jakob disease (sCJD) and positive IgLON5 antibodies (Abs) in the serum and CSF. Case report: A 66-year-old Chinese man presented to the hospital with a stroke-like episode, followed by rapidly progressive cognitive decline, mutism, and parkinsonism. The MRI results showed a cortical ribboning sign in diffusion-weighted MRI, periodic triphasic waves with a slow background in EEG, and positive protein 14-3-3 in CSF. There were matching IgLON5 Abs in the serum and CSF. A literature review showed positive autoimmune encephalitis Abs or autoimmune inflammatory disease between 0.5 and 8.6% among patients with clinical suspicion of CJD, most commonly anti-voltage-gated potassium channel (VGKC) complex and anti-N-methyl-D-aspartate receptor (NMDAR) Abs; however, IgLON5 autoimmunity in CJD has been rarely reported. This is an intriguing association as both conditions have been associated with brain deposits of phosphorylated tau protein. Conclusion: IgLON5 Abs may be observed in patients with a diagnosis of CJD; it is unknown whether a synergistic effect of IgLON5 Abs with CJD exists, increasing neurodegenerative changes.

Integrative Chinese-Western medicine strategy to overcome docetaxel resistance in prostate cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicines (TCMs) have emerged as a promising complementary therapy in the management of prostate cancer (PCa), particularly in addressing resistance to Docetaxel (DTX) chemotherapy. AIM OF THE REVIEW: This review aims to elucidate the mechanisms underlying the development of resistance to DTX in PCa and explore the innovative approach of integrating TCMs in PCa treatment to overcome this resistance. Key areas of investigation include alterations in microtubule proteins, androgen receptor and androgen receptor splice variant 7, ERG rearrangement, drug efflux mechanisms, cancer stem cells, centrosome clustering, upregulation of the PI3K/AKT signaling pathway, enhanced DNA damage repair capability, and the involvement of neurotrophin receptor 1/protein kinase C. MATERIALS AND METHODS: With "Prostate cancer", "Docetaxel", "Docetaxel resistance", "Natural compounds", "Traditional Chinese medicine", "Traditional Chinese medicine compound", "Medicinal plants" as the main keywords, PubMed, Web of Science and other online search engines were used for literature retrieval. RESULTS: Our findings underscore the intricate interplay of molecular alterations that collectively contribute to the resistance of PCa cells to DTX. Moreover, we highlight the potential of TCMs as a promising complementary therapy, showcasing their ability to counteract DTX resistance and enhance therapeutic efficacy. CONCLUSION: The integration of TCMs in PCa treatment emerges as an innovative approach with significant potential to overcome DTX resistance. This review not only provides insights into the mechanisms of resistance but also presents new prospects for improving the clinical outcomes of patients with PCa undergoing DTX therapy. The comprehensive understanding of these mechanisms lays the foundation for future research and the development of more effective therapeutic interventions.

[Orthopaedic robot assisted femoral neck dynamic cross fixation system for the treatment of femoral neck fractures].

OBJECTIVE: To explore and compare the clinical efficacy of orthopedic robot assisted femoral neck system （FNS） and traditional manual FNS in the treatment of femoral neck fractures in middle-aged and young people. METHODS: The clinical data of 62 consecutive patients with femoral neck fracture and age less than 65 years old admitted to the Intelligent Orthopaedic Department of Beijing Jishuitan Hospital from June 2021 to June 2022 were retrospectively analyzed. According to whether orthopedic robot-assisted surgery the patients were divided into two groups：30 patients aged 34 to 56 years old were treated with orthopedic robot assisted FNS internal fixation after closed or limited open reduction（experimental group）； 32 patients aged 33 to 54 years old underwent FNS internal fixation after closed or limited open reduction（control group）. The age, gender, time from injury to admission, average hospital stay, surgical duration, intraoperative bleeding volume, and intraoperative fluoroscopy frequency of two groups of patients were analyzed and compared. The hip joint function in both groups of patients was evaluated using the Harris hip joint scoring standard at 6 months after surgery. RESULTS: All 62 patients with femoral neck fractures successfully completed the surgery. There was no significant difference（P>0.05） between the experimental group and the control group in terms of baseline data such as age, gender, time from injury to admission, time from admission to surgery and the intraoperative bleeding. The surgical duration of the experimental group was significantly shorter than that of the control group [42.1（28.5, 50.7）min vs. 53.4（36.9, 62.5） min, Z=-2.338, P=0.019]. The intraoperative X-ray fluoroscopy frequency of the experimental group was significantly lower than that of the control group[8.0 （6.0, 11.0） times vs. 15.0（13.0, 17.0） times, Z=-5.960, P<0.001]. In terms of postoperative hip joint function, there was no significant difference in Harris score between the two groups of patients at 6-month follow-up（P>0.05）. CONCLUSION: Compared with manual operation of FNS, orthopedic robot assisted FNS in the treatment of femoral neck fractures can help shorten surgical time, reduce intraoperative fluoroscopy frequency, and have similar therapeutic effects on long-term hip joint function recovery.

[Analysis of the efficacy of high tibial osteotomy combined with medial meniscus centralization in knee osteoarthritis].

OBJECTIVE: To explore the efficacy of high tibial osteotomy （HTO） combined with medial meniscus centralization in knee osteoarthritis. METHODS: A total of 26 patients who underwent surgery from October 2018 to October 2020 were reviewed. Among them, 14 patients underwent high tibial osteotomy combined with arthroscopic meniscus centralization surgery were centralized group, including 8 males and 6 females, with an average age of （50.2±1.4） years old and follow-up time of （16.8±4.0） months. Twelve patients with high tibial osteotomy were in the control group, including 6 males and 6 females, with an average age of （50.9±1.8） years and follow-up time of （19.0±4.8） months. Operation time, the knee Lysholm score, knee 2000 IKDC score, MRI, femoral tibial angle（FTA）, hip knee ankle angle （HKA）, and intraoperative and postoperative complications were recorded. RESULTS: All the incisions healed without any complication. The operation time in the centralized group was longer than that in the control group[（65.0±2.1）min vs（52.0±2.1）min, P<0.05]. The medial meniscus extrusion reduction value in the centralized group was significantly reduced compared with the control group[（2.8±1.4） mm vs （1.1±2.2） mm, P<0.05]. The FTA, HKA, knee Lyshlom score, and 2000 IKDC score between two groups were no significantly （P>0.05）. Postoperative knee Lyshlom score and knee 2000 IKDC score improved in both groups（P<0.05）. CONCLUSION: HTO combined with centralization of medial meniscus can improve the reduction of medial meniscus and improve knee function. The medium and long-term curative effect still needs long-term follow-up of more cases.

Transcranial Doppler cerebrovascular reactivity: Thresholds for clinical significance in cerebrovascular disease.

BACKGROUND AND PURPOSE: Thresholds for abnormal transcranial Doppler cerebrovascular reactivity (CVR) studies are poorly understood, especially for patients with cerebrovascular disease. Using a real-world cohort with cerebral arterial stenosis, we sought to describe a clinically significant threshold for carbon dioxide reactivity (CO2R) and vasomotor range (VMR). METHODS: CVR studies were performed during conditions of breathing room air normally, breathing 8% carbon dioxide air mixture, and hyperventilation. The mean and standard deviation (SD) of CO2R and VMR were calculated for the unaffected side in patients with unilateral stenosis; a deviation of 2 SDs below the mean was chosen as the threshold for abnormal. Receiver operating characteristic (ROC) curves for both sides for patients with unilateral and bilateral stenosis were evaluated for sensitivity (Sn) and specificity (Sp). RESULTS: A total of 133 consecutive CVR studies were performed on 62 patients with stenosis with mean±SD age 55±16 years. Comorbidities included hypertension (60%), diabetes (15%), stroke (40%), and smoking (35%). In patients with unilateral stenosis, mean±SD CO2R for the unaffected side was 1.86±0.53%, defining abnormal CO2R as <0.80%. Mean±SD CO2R for the affected side was 1.27±0.90%. The CO2R threshold predicted abnormal acetazolamide single-photon emission computed tomography (SPECT) (Sn = .73, Sp = .79), CT/MRI perfusion abnormality (Sn = .42, Sp = .77), infarction on MRI (Sn = .45, Sp = .76), and pressure-dependent exam (Sn = .50, Sp = .76). For the unaffected side, mean±SD VMR was 39.5±15.8%, defining abnormal VMR as <7.9%. For the affected side, mean±SD VMR was 26.5±17.8%. The VMR threshold predicted abnormal acetazolamide SPECT (Sn = .46, Sp = .94), infarction on MRI (Sn = .27, Sp = .94), and pressure-dependent exam (Sn = .31, Sp = .90). CONCLUSIONS: In patients with multiple vascular risk factors, a reasonable threshold for clinically significant abnormal CO2R is <0.80% and VMR is <7.9%. Noninvasive CVR may aid in diagnosing and risk stratifying patients with stenosis.

Development of a nomogram to predict 30-day mortality of sepsis patients with gastrointestinal bleeding: An analysis of the MIMIC-IV database.

Background: We aimed to establish and validate a prognostic nomogram model for improving the prediction of 30-day mortality of gastrointestinal bleeding (GIB) in critically ill patients with severe sepsis. Methods: In this retrospective study, the current retrospective cohort study extracted data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, then partitioned the cohort randomly into training and validation subsets. The cohort was partitioned into training and validation subsets randomly. Our primary endpoint was 30-day all-cause mortality. To reduce data dimensionality and identify predictive variables, the least absolute shrinkage and selection operator (LASSO) regression was employed. A prediction model was constructed by multivariate logistic regression. Model performance was evaluated using the concordance index (C-index), receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Results: The analysis included 1435 total patients, comprising 1005 in the training cohort and 430 in the validation cohort. We found that age, smoking status, glucose, (BUN), lactate, Sequential Organ Failure Assessment (SOFA) score, mechanical ventilation≥48h (MV), parenteral nutrition (PN), and chronic obstructive pulmonary disease (COPD) independently influenced mortality in sepsis patients with concomitant GIB. The C-indices were 0.746 (0.700-0.792) and 0.716 (0.663-0.769) in the training and validation sets, respectively. Based on the area under the curve (AUC) and DCA, the nomogram exhibited good discrimination for 30-day all-cause mortality in sepsis with GIB. Conclusions: For sepsis patients complicated with GIB, we created a unique nomogram model to predict the 30-day all-cause mortality. This model could be a significant therapeutic tool for clinicians in terms of personalized treatment and prognosis prediction.

SN2 Reaction at the Amide Nitrogen Center Enables Hydrazide Synthesis.

Nucleophilic substitutions are fundamentally important transformations in synthetic organic chemistry. Despite the substantial advances in bimolecular nucleophilic substitutions (SN2) at saturated carbon centers, analogous SN2 reaction at the amide nitrogen atom remains extremely limited. Here we report an SN2 substitution method at the amide nitrogen atom with amine nucleophiles for nitrogen-nitrogen (N-N) bond formation that leads to a novel strategy toward biologically and medicinally important hydrazide derivatives. We found the use of sulfonate-leaving groups at the amide nitrogen atom played a pivotal role in the reaction. This new N-N coupling reaction allows the use of O-tosyl hydroxamates as electrophiles and readily available amines, including acyclic aliphatic amines and saturated N-heterocycles as nucleophiles. The reaction features mild conditions, broad substrate scope (>80 examples), excellent functional group tolerability, and scalability. The method is applicable to late-stage modification of various approved drug molecules, thus enabling complex hydrazide scaffold synthesis.

Race or ethnicity and education in cardiac rehabilitation enrollment.

BACKGROUND: Although cardiac rehabilitation (CR) has established benefits for cardiovascular health, it remains significantly underutilized, with substantial differences in participation related to factors such as educational attainment (EA), race, and ethnicity. We studied a geographically and racially diverse cohort of insured individuals in a health claims database to (1) evaluate differences in CR participation by EA and race or ethnicity and (2) assess how EA modifies associations between race or ethnicity and CR participation. METHODS: We conducted a retrospective cohort study of individuals identified in Optum's de-identified Clinformatics® database between 1/1/2016 and 12/31/2019. Eligible individuals included those aged ≥18 years with a hospitalization for an incident CR-qualifying diagnosis. We calculated incidence rates of CR enrollment by EA and race or ethnicity, as well as associations of EA and race or ethnicity with CR enrollment, and evaluated interaction between EA and race or ethnicity with respect to CR participation. RESULTS: We identified 171,297 individuals eligible for CR with a mean ±â€¯SD age of 70.4 ±â€¯11.6 years; 37.4 % were female, and 68.3 % had >high school education. We observed a dose-response association between EA and rate of participation in CR. After adjustment, compared to White individuals, the odds of attending CR was 24 % lower for Asian individuals [95 % confidence interval (CI): 17 %, 30 %], 13 % lower for Black individuals (95 % CI: 9 %, 17 %), and 32 % lower for Hispanic individuals (95 % CI: 28 %, 35 %), all p < 0.0001. However, Black individuals with ≥bachelor's degree had a similar odds of CR enrollment as White individuals with ≥bachelor's degree (odds ratio 1.01, 95 % CI: 0.85, 1.20, p = 0.95). CONCLUSIONS: EA was positively associated with CR enrollment across racial and ethnic groups. Higher EA might partially attenuate racial and ethnic differences in CR participation, but significant disparities persist. Our findings support increased attention to individuals with limited education to improve CR enrollment.

The respiratory enzyme complex Rnf is vital for metabolic adaptation and virulence in Fusobacterium nucleatum.

IMPORTANCE: This paper illuminates the significant question of how the oral commensal Fusobacterium nucleatum adapts to the metabolically changing environments of several extra-oral sites such as placenta and colon to promote various diseases as an opportunistic pathogen. We demonstrate here that the highly conserved Rhodobacter nitrogen-fixation complex, commonly known as Rnf complex, is key to fusobacterial metabolic adaptation and virulence. Genetic disruption of this Rnf complex causes global defects in polymicrobial interaction, biofilm formation, cell growth and morphology, hydrogen sulfide production, and ATP synthesis. Targeted metabolomic profiling demonstrates that the loss of this respiratory enzyme significantly diminishes catabolism of numerous amino acids, which negatively impacts fusobacterial virulence as tested in a preterm birth model in mice.