Two-photon absorption flexible photodetector responsive to femtosecond laser.

Integrated on-chip femtosecond (fs) laser optoelectronic system, with photodetector as a critical component for light-electrical signal conversion, is a long-sought-after goal for a wide range of frontier applications. However, the high laser peak intensity and complicated nanophotonic waveguide structure of on-chip fs laser are beyond the detectability and integrability of conventional photodetectors. Therefore, flexible photodetector with the response on intense fs laser is in urgent needs. Herein, we demonstrate the first (to our knowledge) two-photon absorption (TPA) flexible photodetector based on the strong TPA nonlinearity of layered hybrid perovskite (IA)2(MA)2Pb3Br10, exhibiting efficient sub-bandgap response on the infrared fs laser at 700-1000 nm. High saturation intensity up to ∼3.8 MW/cm2 is achieved. The device also shows superior current stability even after bending for 1000 cycles. This work may pave the new way for the application of flexible optoelectronics specialized in integrated fs-laser detection.

Intraperitoneal administration of carcinoembryonic antigen-directed chimeric antigen receptor T cells is a robust delivery route for effective treatment of peritoneal carcinomatosis from colorectal cancer in pre-clinical study.

BACKGROUND AIMS: Peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is a highly challenging disease to treat. Systemic chimeric antigen receptor (CAR) T cells have shown impressive efficacy in hematologic malignancies but have been less effective in solid tumors. We explored whether intraperitoneal (i.p.) administration of CAR T cells could provide an effective and robust route of treatment for PC from CRC. METHODS: We generated second-generation carcinoembryonic antigen (CEA)-specific CAR T cells. Various animal models of PC with i.p. and extraperitoneal metastasis were treated by i.p. or intravenous (i.v.) administration of CEA CAR T cells. RESULTS: Intraperitoneally administered CAR T cells exhibited superior anti-tumor activity compared with systemic i.v. cell infusion in an animal model of PC. In addition, i.p. administration conferred a durable effect and protection against tumor recurrence and exerted strong anti-tumor activity in an animal model of PC with metastasis in i.p. or extraperitoneal organs. Moreover, compared with systemic delivery, i.p. transfer of CAR T cells provided increased anti-tumor activity in extraperitoneal tumors without PC. This phenomenon was further confirmed in an animal model of pancreatic carcinoma after i.p. administration of our newly constructed prostate stem cell antigen-directed CAR T cells. CONCLUSIONS: Taken together, our data suggest that i.p. administration of CAR T cells may be a robust delivery route for effective treatment of cancer.

Phenotypic and mutational spectrum of 17 Chinese patients with Menkes Disease.

BACKGROUND: Menkes Disease (MD) is a fatal X-linked recessive disorder caused by mutations in the ATP7A gene. Severe cases typically die before the age of three. Mild MD and occipital horn syndrome are variants of MD characterized by a less severe phenotype and longer survival. OBJECTIVE: This case series aims to validate previous findings, expand the clinical phenotype, identify novel ATP7A mutations of MD patients. METHODS: Observational data with follow-up were collected from 17 genetically diagnosed Chinese MD patients. RESULTS: All 17 patients exhibited neurological symptoms, including delayed motor milestones (100%) and seizures (58.8%). Unspecific pregnancy or delivery complications occurred in 9 patients (52.9%). The most prevalent connective tissue problems were abnormal hair (76.5%), followed by skeletal and dental abnormalities (52.9%), skin problems (41.2%) and hernia (35.3%). Sensorineural hearing loss (17.6%) was previously unreported. Coronary artery aneurysm and patent foramen ovale (5.9%) were infrequent. One 16-year-old boy carries pathological exon 3-4 deletion, presents novel mild phenotype including short stature and cerebellar ataxia. Out of 13 patients with follow-up (median: 24 months), 7 patients (53.8%) died with median survival of 40 months (range: 21-48 months), 3 patients (23.1%) show severe motor development delay and 2 (15.4%) have refractory epilepsy, only the mild MD patient shows improved cerebellar ataxia. Sixteen ATP7A mutations were identified including 6 small indels (37.5%), 5 nonsense mutations (31.2%), 2 missense mutations (12.5%), 2 exon deletions (12.5%), and 1 splice site mutation (6.25%). Fourteen mutations were novel. CONCLUSIONS: Our study further broadens the phenotypic and genotypic spectrums of Menkes disease.

Meta-analysis of the relationship between the number and location of perivascular spaces in the brain and cognitive function.

BACKGROUND: Cerebral perivascular spaces are part of the cerebral microvascular structure and play a role in lymphatic drainage and the removal of waste products from the brain. Relationships of the number and location of such spaces with cognition are unclear. OBJECTIVE: To meta-analyze available data on potential associations of severity and location of perivascular spaces with cognitive performance. METHODS: We searched PubMed, EMBASE, Web of Science and the Cochrane Central Registry of Controlled Trials for relevant studies published between January 2000 and July 2023. Performance on different cognitive domains was compared to the severity of perivascular spaces in different brain regions using comprehensive meta-analysis. When studies report unadjusted and adjusted means, we use adjusted means for meta-analysis. The study protocol is registered in the PROSPERO database (CRD42023443460). RESULTS: We meta-analyzed data from 26 cross-sectional studies and two longitudinal studies involving 7908 participants. In most studies perivascular spaces was using a visual rating scale. A higher number of basal ganglia perivascular spaces was linked to lower general intelligence and attention. Moreover, increased centrum semiovale perivascular spaces were associated with worse general intelligence, executive function, language, and memory. Conversely, higher hippocampus perivascular spaces were associated with enhanced memory and executive function. Subgroup analyses revealed variations in associations among different disease conditions. CONCLUSIONS: A higher quantity of perivascular spaces in the brain is correlated with impaired cognitive function. The location of these perivascular spaces and the underlying disease conditions may influence the specific cognitive domains that are affected. SYSTEMATIC REVIEW REGISTRATION: The study protocol has been registered in the PROSPERO database (CRD42023443460).

Partial nitrification-denitrification and enrichment of paracoccus induced by iron-chitosan beads addition in an intermittently-aerated activated sludge system.

Insufficient carbon source has become the main limiting factor for efficient nitrogen removal in wastewater treatment. In this study, an intermittently-aerated activated sludge system with iron-chitosan (Fe-CS) beads addition was proposed for nitrogen removal from low C/N wastewater. By adding Fe-CS beads, partial nitrification-denitrification (PND) process and significant enrichment of Paracoccus (with ability of iron reduction/ammonium oxidation/aerobic denitrification) were observed in the reactor. The accumulation rate of NO2--N reached 81.9 %, and the total nitrogen removal efficiency was improved to 93.9 % by shortening the aeration time. The higher activity of ammonium oxidizing bacteria and inhibited activity of nitrite-oxidizing bacteria in Fe-CS assisted system mediated the occurrence of PND. In contrast, the traditional nitrification and denitrification process occurred in the control group. The high-throughput sequencing analysis and metagenomic results confirmed that the addition of Fe-CS induced 77.8 % and 54.9 % enrichment of Paracoccus in sludge and Fe-CS beads, respectively, while almost no enrichment was observed in control group. Furthermore, with the addition of Fe-CS beads, the expression of genes related to outer membrane porin, cytochrome c, and TCA was strengthened, thereby enhancing the electron transport of Fe(Ⅱ) (electron donor) and Fe(Ⅲ) (electron acceptor) with pollutants in the periplasm. This study provides new insights into the direct enrichment of iron-reducing bacteria and its PND performance induced by the Fe-CS bead addition. It therefore offers an appealing strategy for low C/N wastewater treatment.

Proteogenomics in Cancer: Then and Now.

For years, the paths of sequencing technologies and mass spectrometry have occurred in isolation, with each developing its own unique culture and expertise. These two technologies are crucial for inspecting complementary aspects of the molecular phenotype across the central dogma. Integrative multiomics strives to bridge the analysis gap among different fields to complete more comprehensive mechanisms of life events and diseases. Proteogenomics is one integrated multiomics field. Here in this review, we mainly summarize and discuss three aspects: workflow of proteogenomics, proteogenomics applications in cancer research, and the SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis of proteogenomics in cancer research. In conclusion, proteogenomics has a promising future as it clarifies the functional consequences of many unannotated genomic abnormalities or noncanonical variants and identifies driver genes and novel therapeutic targets across cancers, which would substantially accelerate the development of precision oncology.

UV-VIS-NIR broadband flexible photodetector based on layered lead-free organic-inorganic hybrid perovskite.

The flexible photodetector is viewed as a research hotspot for numerous advanced optoelectronic applications. Recent progress has manifested that lead-free layered organic-inorganic hybrid perovskites (OIHPs) are highly attractive to engineering flexible photodetectors due to the effective overlapping of several unique properties, including efficient optoelectronic characteristics, exceptional structural flexibility, and the absence of Pb toxicity to humans and the environment. The narrow spectral response of most flexible photodetectors with lead-free perovskites is still a big challenge to practical applications. In this work, we demonstrate the flexible photodetector based on a novel (to our knowledge) narrow-bandgap OIHP of (BA)2(MA)Sn2I7, with achieving a broadband response across an ultraviolet-visible-near infrared (UV-VIS-NIR) region as 365-1064 nm. The high responsivities of 28.4 and 2.0 × 10-2 A/W are obtained at 365 and 1064 nm, respectively, corresponding to detectives of 2.3 × 1010 and 1.8 × 107 Jones. This device also shows remarkable photocurrent stability after 1000 bending cycles. Our work indicates the huge application prospect of Sn-based lead-free perovskites in high-performance and eco-friendly flexible devices.

Medication Status and Related Factors in Essential Tremor Patients: A Cross-Sectional Study in China.

INTRODUCTION: Essential tremor (ET) is one of the most common movement disorders. Oral drugs play a crucial role in treating ET, with various available options such as propranolol, primidone, and topiramate. However, the medication status and related factors among Chinese ET patients are unknown yet. METHODS: This study used the baseline data from the National Survey of Essential Tremor Plus in China cohort. ET patients with information related to medication intake were included. Medication patients were defined as patients who were taking medication at the time of the survey. We further defined recommended medication users according to Chinese guideline recommendations and clinical knowledge. We used mean and standard deviation (SD), median and interquartile range (IQR), or frequencies and percentages when appropriate for descriptive analysis. We used multivariate logistic regression analyses to explore factors related to medication intake in all ET patients and in recommended medication users. RESULTS: Of 1,153 included ET participants, 207 (18.0%) took medication. Arotinolol (115, 55.6%) and propranolol (63, 30.4%) were the top 2 used medicines. Patients with middle school education (odds ratio 0.57, 95% confidence interval 0.39-0.83), college or higher level education (0.46, 0.28-0.76), and late-onset ET (LO-ET) (0.38, 0.23-0.63) were less likely to take medication. Patients with intention tremor (1.90, 1.38-2.62), every 10-unit increase in age (1.10, 1.00-1.21), Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) Part 1 (1.63, 1.37-1.93), and TETRAS Part 2 (1.81, 1.48-2.22) were more likely to take medication. Among 332 recommended medication users, only 104 (31.3%) took medicine. The associations of LO-ET (0.36, 0.17-0.75), intention tremor (2.27, 1.35-3.81), TETRAS Part 1 (1.52, 1.09-2.13), and TETRAS Part 2 (1.59, 1.15-2.20) with medication were similar to all ET patients. CONCLUSION: The proportion of medication intake is low among both all ET patients and recommended medication users. The top 2 commonly used medications among all ET patients are arotinolol and propranolol. Influencing factors of medication intake are different between all ET patients and recommended medication users. Clinicians are suggested to provide counseling and education on ET medication to promote medication intake.

An S-like curve relationship between systemic inflammation response index (SIRI) and respiratory failure in GBS patients.

BACKGROUND: Our study examined the association between the initial systemic inflammation response index (SIRI) and respiratory failure in patients with Guillain-Barré syndrome (GBS). METHODS: The weighted linear regression model, weighted chi-square test, logistic regression models, smooth curve fittings, and the two-piece linear regression model were utilized for data analysis. RESULTS: Among the 443 GBS patients, 75 (6.9%) had experienced respiratory failure. According to logistic regression models, there existed no consistent linear relationship between respiratory failure and SIRI in model 1 (OR = 1.2, p < 0.001), model 2 (OR = 1.2, p < 0.001), and model 3 (OR = 1.3, p = 0.017). However, smooth curve fittings found an S-like curve relationship between SIRI and respiratory failure. Furthermore, when SIRI was < 6.4, there existed a positive correlation between SIRI and respiratory failure in model 1 (OR = 1.5, 95% CI = (1.3, 1.8), p < 0.0001), higher correlation in model 2 (OR = 1.6, 95% CI = (1.3, 1.8), p < 0.0001), and highest correlation in model 3 (OR = 1.6, 95% CI = (1.3, 2.5), p < 0.0001). CONCLUSIONS: SIRI can be used as a predictor of respiratory failure in GBS, and an S-like relationship exists between SIRI and respiratory failure at an infliction point of 6.4. When the SIRI was less than 6.4 and increased, SIRI was associated with a higher occurrence of respiratory failure. The risk of respiratory failure was no longer increased when the SIRI was over 6.4.

Mitogen-Activated Protein Kinase 15 Is a New Predictive Biomarker and Potential Therapeutic Target for Ovarian Cancer.

Mitogen-activated protein kinase 15 (MAPK15) has been reported to be associated with several cancers. This study aimed to explore for the first time on the relationship between MAPK15 expression and cancer progression/drug responsiveness in ovarian carcinoma. To this end, MAPK15 expression level was examined by immunohistochemistry (IHC) staining of an ovarian tissue array (10 normal and 70 malignant samples). Drug sensitivity of ovarian cancer cell lines (including OVCAR3 and SKOV3) was measured by MTS assay. The modulation of MAPK15 expression in OVCAR3 and SKOV3 was verified by immunoblot and real-time PCR analyses. The prognostic value of MAPK15 in ovarian cancer patients was assessed using the Kaplan-Meier Plotter database and Gene Expression Omnibus (GEO) datasets. The IHC results showed that MAPK15 expression was negatively associated with tumor grade, TNM stage, tumor size, and regional lymph node metastasis of ovarian carcinoma. Importantly, overexpressing MAPK15 increased cisplatin toxicity in ovarian carcinoma cells and online database analysis indicated that patients with high MAPK15 expression had favorable prognosis with/without chemotherapy. Taken together, our results indicate that a decreased MAPK15 expression is associated with advanced-stage ovarian cancer and unfavorable survival outcomes. MAPK15 may be a new biomarker for ovarian cancer, and the encouraging therapeutic strategy would be found by combining the regulation of MAPK15 expression.

Comparison of Human Eukaryotic Translation Initiation Factors 5A1 and 5AL1: Identification of Amino Acid Residues Important for EIF5A1 Lysine 50 Hypusination and Its Protein Stability.

The human eukaryotic translation initiation factor 5A (EIF5A) family consists of three members, namely EIF5A1, EIF5A2, and EIF5AL1. Recent studies have shown that the expression of EIF5As is related to many human diseases, such as diabetes, viral infection, central nervous system injury, and cancer. Among them, EIF5A1 plays different functions in various cancers, possibly as a tumor-suppressor or oncogene, while EIF5A2 promotes the occurrence and development of cancer. Yet, the biological function of EIF5AL1 is not being studied so far. Interestingly, although there are only three amino acid (at residues 36, 45, and 109) differences between EIF5A1 and EIF5AL1, we demonstrate that only EIF5A1 can be hypusinated while EIF5AL1 cannot, and EIF5AL1 has a tumor-suppressor-like function by inhibiting cell proliferation and migration. We also show that EIF5AL1 protein turnover is mediated through the proteasomal pathway, and EIF5AL1 protein turnover is much faster than that of EIF5A1, which may explain their differential protein expression level in cells. By engineering single and double mutations on these three amino acids, we pinpoint which of these amino acids are critical for hypusination and protein stability. The data of this work should fill in the gaps in EIF5As research and pave the way for future studies on EIF5AL1.

The Epigenetic Effects of Coffee.

In this review, we discuss the recent knowledge regarding the epigenetic effects of coffee extract and the three essential active ingredients in coffee (caffeine, chlorogenic acid, and caffeic acid). As a popular beverage, coffee has many active ingredients which have a variety of biological functions such as insulin sensitization, improvement of sugar metabolism, antidiabetic properties, and liver protection. However, recent researches have shown that coffee is not only beneficial for human, but also bad, which may be due to its complex components. Studies suggest that coffee extract and its components can potentially impact gene expression via alteration of DNA methylation, histone modifications, and ncRNA expression; thus, exert long lasting impacts on the epigenome. More importantly, coffee consumption during pregnancy has been linked to multiple negative effects on offspring due to epigenetic modifications; on the other hand, it has also been linked to improvements in many diseases, including cancer. Therefore, understanding more about the epigenetic effects associated with coffee components is crucial to finding ways for improving human health.

Enhanced photothermoelectric detection in Co:BiCuSeO crystals with tunable Seebeck effect.

BiCuSeO is a widely-used thermoelectric material recently proved to be an appealing candidate for broadband photothermoelectric (PTE) detection. Developing a simple and scalable route for advancing PTE properties is therefore essential to explore the full potential of BiCuSeO. Here we systematically demonstrated that Co3+ atomic doping strategies in BiCuSeO single crystals (Co concentration of 1%, 2% and 4%) could modulate the Seebeck coefficient and thus strongly improve the performance of BiCuSeO PTE photodetectors across visible to infrared spectral regions. Benefiting from these strategies, a large enhancement on photovoltage responsivity is achieved and the response time of a 4% Co:BiCuSeO PTE photodetector is one order of magnitude faster than those in most of PTE photodetectors. Also, Co:BiCuSeO PTE photodetectors show good stability with changeless photoresponse after being exposed to air for three months. Therefore, the controllable atomic doping of BiCuSeO with tunable PTE properties as well as fast and broadband photodetection provides the feasibility for facilitating ongoing research toward PTE devices.

Recent knowledge of NFATc4 in oncogenesis and cancer prognosis.

Nuclear factor of activated T-cells, cytoplasmic 4 (NFATc4), a transcription factor of NFAT family, which is activated by Ca2+/calcineurin signaling. Recently, it is reported that aberrantly activated NFATc4 participated and modulated in the initiation, proliferation, invasion, and metastasis of various cancers (including cancers of the lung, breast, ovary, cervix, skin, liver, pancreas, as well as glioma, primary myelofibrosis and acute myelocytic leukemia). In this review, we cover the latest knowledge on NFATc4 expression pattern, post-translational modification, epigenetic regulation, transcriptional activity regulation and its downstream targets. Furthermore, we perform database analysis to reveal the prognostic value of NFATc4 in various cancers and discuss the current unexplored areas of NFATc4 research. All in all, the result from these studies strongly suggest that NFATc4 has the potential as a molecular therapeutic target in multiple human cancer types.

Toxic metals in the regulation of epithelial-mesenchymal plasticity: demons or angels?

Epithelial cells can trans-differentiate into motile mesenchymal cells through a dynamic process known as epithelial-mesenchymal transition (EMT). EMT is crucial in embryonic development and wound healing but also contributes to human diseases such as organ fibrosis and cancer progression. Heavy metals are environmental pollutants that can affect human health in various ways, including causing cancers. The cytotoxicity and carcinogenicity of heavy metals are complex, and studies have demonstrated that some of these metals can affect the progress of EMT. Here, we focus on reviewing the roles of six environmentally common toxic metals concerning EMT: arsenic (AS), cadmium (Cd), cobalt (Co), chromium (Cr), nickel (Ni), and copper (Cu). Noteworthily, the effects of these elements on EMT may vary according to the form, dose, and exposure time; the dual role of heavy metals (e.g., AS, Cd, and Cu) on EMT is also observed, in which, sometimes they can promote while sometimes inhibit the EMT process. Given the vast number of toxicologically relevant metals that exist in nature, we believe a comprehensive understanding of their effects on EMT is required to dictate in what circumstances these metals act more likely as demons or angels.

Clinical features and reclassification of essential tremor with NOTCH2NLC GGC repeat expansions based on a long-term follow-up.

BACKGROUND AND PURPOSE: NOTCH2NLC GGC repeat expansions have been identified to be associated with essential tremor (ET). Our aim was to characterize ET patients with NOTCH2NLC repeat expansions versus non-expansions and describe distinctive clinical features of repeat expanded patients with long-term follow-up according to the new tremor classification. METHODS: Participants included 597 ET pedigrees, 412 sporadic cases and 1085 healthy controls. Repeat expansions of GGC in NOTCH2NLC were screened, and comprehensive clinical features were investigated. A longitudinal clinical assessment and reclassification were performed in NOTCH2NLC expanded patients. RESULTS: In total, 27 ET pedigrees (27/597) and three sporadic patients (3/412) were identified with pathogenic NOTCH2NLC GGC repeat expansions (≥60 repeats). Intermediate-length GGC repeats (41-59 repeats) were found in four sporadic ET cases and one control subject, and the frequency was higher than that in control participants (4/412 vs. 1/1085, p = 0.022). About 46 ET patients (43 familial cases from 27 pedigrees and three sporadic cases) with NOTCH2NLC GGC repeat expansions had higher Essential Tremor Rating Assessment Scale I, Essential Tremor Rating Assessment Scale II and Non-Motor Symptoms Scale scores and lower Mini-Mental State Examination scores than the patients without expansions. Patients with pathogenic GGC repeats were reclassified as pure ET (25/46), ET-plus (11/46) and ET-neuronal intranuclear inclusion disease (10/46) subgroups at 2-8 years of follow-up. CONCLUSION: Our results further supported that NOTCH2NLC GGC repeat expansions were associated with ET. Patients with pathogenic GGC repeats presented with more severe motor and non-motor symptoms. Further long-term follow-up and subtype studies will help to define the role of NOTCH2NLC in ET.

Development and validation of a nomogram for freezing of gait in patients with Parkinson's Disease.

OBJECTIVES: Freezing of gait (FOG) is a common and complex disabling episodic gait disturbance in patients with Parkinson's disease (PD). Currently, the treatment of FOG remains a challenge for clinicians. The aim of our study was to develop a nomogram for FOG risk based on data collected from Chinese patients with PD. MATERIALS & METHODS: A total of 379 PD patients (197 with FOG) from Kunming Medical University were recruited as a training cohort. Additionally, 339 PD patients (166 with FOG) were recruited from West China Hospital of Sichuan University, to serve as the validation cohort. The least absolute shrinkage and selection operator regression model was used to select clinical and demographic characteristics as well as blood markers, which were incorporated into a predictive model using multivariate logistic regression to predict the risk of developing FOG. The model was validated using the validation dataset, and model performance was evaluated using the C-index, calibration plot, and decision curve analyses. RESULTS: The final predictive model included the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) score, Parkinson's Disease Questionnaire (PDQ39), H-Y stage, and visuospatial function. The model showed good calibration and good discrimination, with a C-index value of 0.772 against the training cohort and 0.766 against the validation cohort. Decision curve analysis demonstrated the clinical utility of the nomogram. CONCLUSION: A nomogram incorporating RBDSQ, PDQ39, H-Y stage, and visuospatial function may reliably predict the risk of FOG in PD patients.

Oculopharyngodistal myopathy with CGG repeat expansions in GIPC1: the first report from southwestern China.

Oculopharyngodistal myopathy (OPDM) is a rare adult-onset hereditary muscular disease characterized by slowly progressive ptosis, external ophthalmoplegia and weakness of the facial, pharyngeal and distal limb muscles. Recently, CGG repeat expansion mutations in three genes, LRP12, GIPC1 and NOTCH2NLC, have been identified as causative factors for OPDM. Here, we report clinicopathologically typical familial OPDM patients from southwestern China. CGG repeat expansions in GIPC1 were detected in two OPDM-affected individuals. Our study was the first GIPC1-OPDM report from southwestern China, further confirming expanded GGC repeats in GIPC1 as the cause of OPDM.

Prevalence and associated factors of frailty and sarcopenia in multiple system atrophy and progressive supranuclear palsy: a cross-sectional study.

OBJECTIVE: To investigate the prevalence of, and clinicodemographic factors associated with, frailty and sarcopenia in patients with multiple system atrophy or progressive supranuclear palsy. METHODS: A total of 264 participants were recruited in this study. Demographic and clinical data were collected through structured interviews. Frailty was assessed with the clinical frailty scale (CFS), and sarcopenia was assessed with the simple five-item scoring questionnaire (SARC-F). RESULTS: The prevalence of frailty and sarcopenia was 48.57% and 35.71% in multiple system atrophy, and 51.09% and 39.13% in progressive supranuclear palsy. Multiple system atrophy patients with frailty or sarcopenia were more likely to be female and have longer disease duration, greater motor impairment, greater non-motor burden, and lower life quality. In multiple system atrophy, frailty was associated with reduced motor function and sarcopenia was associated with female sex, reduced motor function, and orthostatic hypotension. Progressive supranuclear palsy patients with frailty or sarcopenia had more severe motor impairment and non-motor burden, longer disease duration, and lower life quality. In progressive supranuclear palsy, frailty was associated with mentation and gait/midline symptoms, while sarcopenia was associated with reduced daily activity and severe gait/midline symptoms. CONCLUSION: Frailty and sarcopenia may be more common among patients with multiple system atrophy or progressive supranuclear palsy than among the general population, and they are associated with more severe forms of the two diseases. Prospective studies are necessary to clarify causal relationships between frailty/sarcopenia and clinical manifestations of multiple system atrophy and progressive supranuclear palsy.

Cytochrome P450 27C1 Level Dictates Lung Cancer Tumorigenicity and Sensitivity towards Multiple Anticancer Agents and Its Potential Interplay with the IGF-1R/Akt/p53 Signaling Pathway.

Cytochrome P450 enzymes (CYP450s) exert mighty catalytic actions in cellular metabolism and detoxication, which play pivotal roles in cell fate determination. Preliminary data shows differential expression levels of CYP27C1, one of the "orphan P450s" in human lung cancer cell lines. Here, we study the functions of CYP27C1 in lung cancer progression and drug endurance, and explore its potential to be a diagnostic and therapeutic target for lung cancer management. Quantitative real-time PCR and immunoblot assays were conducted to estimate the transcription and protein expression level of CYP27C1 in human lung cancer cell lines, which was relatively higher in A549 and H1975 cells, but was lower in H460 cells. Stable CYP27C1-knockdown A549 and H1975 cell lines were established, in which these cells showed enhancement in cell proliferation, colony formation, and migration. In addition, aberrant IGF-1R/Akt/p53 signal transduction was also detected in stable CYP27C1-knockdown human lung cancer cells, which exhibited greater tolerance towards the treatments of anticancer agents (including vinorelbine, picropodophyllin, pacritinib, and SKLB610). This work, for the first time, reveals that CYP27C1 impacts lung cancer cell development by participating in the regulation of the IGF-1R/Akt/p53 signaling pathway, and the level of CYP27C1 plays indispensable roles in dictating the cellular sensitivity towards multiple anticancer agents.