Diagnostic accuracy of procalcitonin in adult non-neutropenic cancer patients with suspected infection: a systematic review and meta-analysis.

BACKGROUND: Procalcitonin (PCT) has garnered attention as a potential diagnostic biomarker for infection in cancer patients. We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of procalcitonin (PCT) and to compare it with C-reactive protein (CRP) in adult non-neutropenic cancer patients with suspected infection. METHODS: A systematic literature search was performed in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify all relevant diagnostic accuracy studies. Original articles reporting the diagnostic accuracy of PCT for infection detection in adult patients with solid or hematological malignancies were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, area under the hierarchical summary receiver operator characteristic (HSROC) curve, and corresponding 95% confidence interval (CI) were calculated. RESULTS: Seven studies were included in the meta-analysis. The pooled sensitivity and specificity of PCT were 60% (95% CI [45-74%]) and 78% (95% CI [69-86%]). The diagnostic odds ratio was estimated at 5.47 (95% CI [2.86-10.46]). Three studies compared the diagnostic accuracies of PCT and CRP. The pooled sensitivity and specificity values for PCT were 57% (95% CI [26-83%]) and 75% (95% CI [68-82%]), and those for CRP were 67% (95% CI [35-88%]) and 73% (95% CI [69-77%]). The pooled sensitivity and specificity of PCT and CRP did not differ significantly (p = 0.61 and p = 0.63). The diagnostic accuracy of PCT was similar to that of CRP as measured by the area under the HSROC curve (0.73, CI = 0.61-0.91 vs. 0.74, CI = 0.61-0.95, p = 0.93). CONCLUSION: While elevated PCT levels can be indicative of potential infection, they should not be solely relied upon to exclude infection. We recommend not using the PCT test in isolation; Instead, it should be carefully interpreted in the context of clinical findings.

Clinical outcome of bevacizumab or ramucirumab combined with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as the first line therapy in susceptible EGFR-mutated advanced non-small-cell lung.

Combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with an anti- vascular endothelial growth factor (VEGF) agent, bevacizumab or ramucirumab, is indicated for advanced lung adenocarcinoma harboring EGFR mutation. This study aimed to show the real-world data of combination therapy and compare the effectiveness between bevacizumab and ramucirumab in combination with an EGFR-TKI. This retrospective study enrolled 47 patients diagnosed of stage IV lung adenocarcinoma with exon 19 deletion or L858R point mutation, receiving a first-line EGFR-TKI with anti-VEGF agent, including 34 (72%) and 13 (28%) patients receiving bevacizumab and ramucirumab, respectively. The response rate was similar in both groups (p = 0.38). Patients receiving bevacizumab had similar progression free survival (PFS) as those receiving ramucirumab (median PFS: 21.9 vs. 24.2 months, p = 0.4871); similar finding was noted in overall survival (OS) (median OS: 33.5 months vs. not reached, p = 0.4618). Patients receiving ramucirumab experienced a significantly high-grade hypertension compared to those receiving bevacizumab (p = 0.0351). Multivariable Cox regression analysis found independent risk factors for worse PFS included poorer ECOG performance status, multiple (≥3) metastatic sites, brain metastasis, and pleural metastasis/effusion, while the type of anti-VEGF agent was not a risk factor. Pericardial metastasis/effusion was the only one independent risk factor for worse OS. In summary, ramucirumab may have similar effectiveness as bevacizumab in combination with an EGFR-TKI as first line therapy for advanced lung adenocarcinoma harboring susceptible EGFR mutation. Further large-scale registry-based cohort studies may be needed to validate our findings.

Comparing transfusion reactions between pre-storage and post-storage leukoreduced apheresis platelets: an analysis using propensity score matching.

Transfusion reactions induced by platelet transfusions may be reduced and alleviated by leukocyte reduction of platelets. Although leukoreduction of apheresis platelets can be performed either pre-storage or post-storage, seldom studies directly compare the incidence of transfusion reaction in these two different blood products. We conducted a retrospective study to compare the transfusion reactions between pre-storage and post-storage leukoreduced apheresis platelets. We reviewed the general characteristics and the transfusion reactions, symptoms, and categories for inpatients who received pre-storage or post-storage leukoreduced apheresis platelets. Propensity-score matching was performed to adjust for baseline differences between groups. A total of 40,837 leukoreduction apheresis platelet orders were reviewed. 116 (0.53%) transfusion reactions were reported in 21,884 transfusions with pre-storage leukoreduction, and 174 (0.91%) reactions were reported in 18,953 transfusions with post-storage leukoreduction. Before propensity-score matching, the odds ratio for transfusion reactions in the pre-storage group relative to the post-storage group was 0.57 (95% confidence interval [CI] 0.45-0.72, P < 0.01); the odds ratio after matching was 0.63 (95% CI 0.49-0.80, P < 0.01). A two-proportion z-test revealed pre-storage leukoreduction significantly decreases the symptoms of chills, fever, itching, urticaria, dyspnea, and hypertension as compared with those in post-storage leukoreduction. Pre-storage leukoreduced apheresis platelet significantly decreased febrile non-hemolytic transfusion reaction as compared with post-storage groups. This study suggests pre-storage leukoreduction apheresis platelet significantly decreases the transfusion reaction as compared with those in post-storage leukoreduction.

Enhancing Electrochemical Non-Enzymatic Dopamine Sensing Based on Bimetallic Nickel/Cobalt Phosphide Nanosheets.

In this study, the successful synthesis of bimetallic nickel/cobalt phosphide nanosheets (Ni-Co-P NSs) via the hydrothermal method and the subsequent high-temperature phosphorization process were both confirmed. Ni-Co-P NSs exhibited excellent electrocatalytic activity for the electrochemical non-enzymatic DA sensing. The surface morphologies and physicochemical properties of Ni-Co-P NSs were characterized by atomic force microscopy (AFM), field-emission scanning (FESEM), field-emission transmission electron microscopy (FETEM), and X-ray diffraction (XRD). Further, the electrochemical performance was evaluated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The metallic nature of phosphide and the synergistic effect of Ni/Co atoms in Ni-Co-P NSs provided abundant catalytic active sites for the electrochemical redox reaction of DA, which exhibited a remarkable consequence with a wide linear range from 0.3~50 µM, a high sensitivity of 2.033 µA µM-1 cm-2, a low limit of detection of 0.016 µM, and anti-interference ability. As a result, the proposed Ni-Co-P NSs can be considered an ideal electrode material for the electrochemical non-enzymatic DA sensing.

Local Consolidative Therapy May Have Prominent Clinical Efficacy in Patients with EGFR-Mutant Advanced Lung Adenocarcinoma Treated with First-Line Afatinib.

Afatinib is an irreversible tyrosine kinase inhibitor (TKI) targeting the epidermal growth factor receptor (EGFR), which is utilized for the treatment of patients with advanced lung cancer that harbors EGFR mutations. No studies have evaluated the clinical efficacy of LCT in patients treated with first-line afatinib. In this study, we retrospectively enrolled patients with advanced lung adenocarcinomas harboring susceptible EGFR mutations who were diagnosed and treated with first-line afatinib in three hospitals. A total of 254 patients were enrolled, including 30 (12%) patients who received LCT (15 patients received definitive radiotherapy for the primary lung mass and 15 patients received curative surgery). Patients who received LCT had a significantly longer PFS than those who did not (median PFS: 32.8 vs. 14.5 months, p = 0.0008). Patients who received LCT had significantly longer OS than those who did not (median OS: 67.1 vs. 34.5 months, p = 0.0011). Multivariable analysis showed LCT was an independent prognostic factor for improved PFS (adjusted hazard ratio [aHR] [95% confidence interval (CI)]: 0.44 [0.26-0.73], p = 0.0016) and OS (aHR [95% CI]: 0.26 [0.12-0.54], p = 0.0004). The analyses using propensity score-weighting showed consistent results. We conclude that LCT may improve clinical outcomes, in terms of PFS and OS, in patients with advanced EGFR-mutant lung adenocarcinomas who are treated with first-line afatinib.

Pulmonary alveolar proteinosis in Taiwan.

BACKGROUND/PURPOSE: Pulmonary alveolar proteinosis (PAP) is rare disease manifested as alveolar macrophage dysfunction and abnormal accumulation of surfactant protein in the alveoli. In this nationwide, population-based study, we investigated the epidemiology of PAP in Taiwan, and discovered the comorbidities and prognostic factors of PAP. METHODS: From the National Health Insurance Research Database (NHIRD), we obtained comprehensive information about all patients of PAP in Taiwan between 1995 and 2013. The incidence, baseline characteristics comorbidities, and prognostic factors of PAP were investigated. RESULTS: The annual incidence rate of PAP was around 0.79 (range: 0.49-1.17) patients per million people after 2000, and the prevalence rate was 7.96 patients per million people by the end of 2013. In total, 276 patients of PAP were identified, including 177 (64%) and 99 (36%) patients with primary and secondary PAP, respectively. The median age of diagnosis was 53.8 years. The median survival was 9.6 years after the initial PAP diagnosis, and the 5-year survival rate was 65.96%. Twenty (7%) patients received whole lung lavage (WLL) within three months after the diagnosis had significantly better survival compared to the others. Multivariable Cox regression analyses showed that elder age, secondary PAP, and malignancy were associated with poorer survival, while WLL within 3 months of diagnosis might greatly improve the survival. CONCLUSION: We demonstrated the epidemiology of PAP in Taiwan, showing several poor prognostic factors and the potential effectiveness of WLL. Further prospective studies based on registry are warranted to improve the diagnosis and treatment of PAP.

Electrochemical Organophosphorus Pesticide Detection Using Nanostructured Gold-Modified Electrodes.

In this study, nanostructured gold was successfully prepared on a bare Au electrode using the electrochemical deposition method. Nanostructured gold provided more exposed active sites to facilitate the ion and electron transfer during the electrocatalytic reaction of organophosphorus pesticide (methyl parathion). The morphological and structural characterization of nanostructured gold was conducted using field-emission scanning electron microscopy (FESEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD), which was further carried out to evaluate the electrocatalytic activity towards methyl parathion sensing. The electrochemical performance of nanostructured gold was investigated by electrochemical measurements (cyclic voltammetry (CV) and differential pulse voltammetry (DPV)). The proposed nanostructured gold-modified electrode exhibited prominent electrochemical methyl parathion sensing performance (including two linear concentration ranges from 0.01 to 0.5 ppm (R2 = 0.993) and from 0.5 to 4 ppm (R2 = 0.996), limit of detection of 5.9 ppb, excellent selectivity and stability), and excellent capability in determination of pesticide residue in real fruit and vegetable samples (bok choy and strawberry). The study demonstrated that the presented approach to fabricate a nanostructured gold-modified electrode could be practically applied to detect pesticide residue in agricultural products via integrating the electrochemical and gas chromatography coupled with mass spectrometry (GC/MS-MS) analysis.

Mesenchymal Stem Cell Secreted-Extracellular Vesicles are Involved in Chondrocyte Production and Reduce Adipogenesis during Stem Cell Differentiation.

BACKGROUND: Extracellular vesicles (EVs) are derived from internal cellular compartments, and have potential as a diagnostic and therapeutic tool in degenerative disease associated with aging. Mesenchymal stem cells (MSCs) have become a promising tool for functional EVs production. This study investigated the efficacy of EVs and its effect on differentiation capacity. METHODS: The characteristics of MSCs were evaluated by flow cytometry and stem cell differentiation analysis, and a production mode of functional EVs was scaled from MSCs. The concentration and size of EVs were quantitated by Nanoparticle Tracking Analysis (NTA). Western blot analysis was used to assess the protein expression of exosome-specific markers. The effects of MSC-derived EVs were assessed by chondrogenic and adipogenic differentiation analyses and histological observation. RESULTS: The range of the particle size of adipose-derived stem cells (ADSCs)- and Wharton's jelly -MSCs-derived EVs were from 130 to 150 nm as measured by NTA, which showed positive expression of exosomal markers. The chondrogenic induction ability was weakened in the absence of EVs in vitro. Interestingly, after EV administration, type II collagen, a major component in the cartilage extracellular matrix, was upregulated compared to the EV-free condition. Moreover, EVs decreased the lipid accumulation rate during adipogenic induction. CONCLUSION: The results indicated that the production model could facilitate production of effective EVs and further demonstrated the role of MSC-derived EVs in cell differentiation. MSC-derived EVs could be successfully used in cell-free therapy to guide chondrogenic differentiation of ADSC for future clinical applications in cartilage regeneration.

Spatiotemporal gating of Stat nuclear influx by Drosophila Npas4 in collective cell migration.

Collective migration is important to embryonic development and cancer metastasis, but migratory and nonmigratory cell fate discrimination by differential activity of signal pathways remains elusive. In Drosophila oogenesis, Jak/Stat signaling patterns the epithelial cell fates in early egg chambers but later renders motility to clustered border cells. How Jak/Stat signal spatiotemporally switches static epithelia to motile cells is largely unknown. We report that a nuclear protein, Dysfusion, resides on the inner nuclear membrane and interacts with importin α/ß and Nup153 to modulate Jak/Stat signal by attenuating Stat nuclear import. Dysfusion is ubiquitously expressed in oogenesis but specifically down-regulated in border cells when migrating. Increase of nuclear Stat by Dysfusion down-regulation triggers invasive cell behavior and maintains persistent motility. Mammalian homolog of Dysfusion (NPAS4) also negatively regulates the nuclear accumulation of STAT3 and cancer cell migration. Thus, our finding demonstrates that Dysfusion-dependent gating mechanism is conserved and may serve as a therapeutic target for Stat-mediated cancer metastasis.

WAKE-mediated modulation of cVA perception via a hierarchical neuro-endocrine axis in Drosophila male-male courtship behaviour.

The nervous and endocrine systems coordinate with each other to closely influence physiological and behavioural responses in animals. Here we show that WAKE (encoded by wide awake, also known as wake) modulates membrane levels of GABAA receptor Resistance to Dieldrin (Rdl), in insulin-producing cells of adult male Drosophila melanogaster. This results in changes to secretion of insulin-like peptides which is associated with changes in juvenile hormone biosynthesis in the corpus allatum, which in turn leads to a decrease in 20-hydroxyecdysone levels. A reduction in ecdysone signalling changes neural architecture and lowers the perception of the male-specific sex pheromone 11-cis-vaccenyl acetate by odorant receptor 67d olfactory neurons. These finding explain why WAKE-deficient in Drosophila elicits significant male-male courtship behaviour.

Constructing Morphologically Tunable Copper Oxide-Based Nanomaterials on Cu Wire with/without the Deposition of Manganese Oxide as Bifunctional Materials for Glucose Sensing and Supercapacitors.

Morphologically tunable copper oxide-based nanomaterials on Cu wire have been synthesized through a one-step alkali-assisted surface oxidation process for non-enzymatic glucose sensing. Subsequently, copper oxide-based nanomaterials on Cu wire as a supporting matrix to deposit manganese oxide for the construction of heterostructured Mn-Cu bimetallic oxide architectures through spontaneous redox reaction in the KMnO4 solution for supercapacitors. Field emission scanning electron microscopy (FESEM), field emission transmission electron microscopy (FETEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) confirmed that morphological and phase transformation from Cu(OH)2 to CuO occurred in copper oxide-based nanomaterials on Cu wire with different degrees of growth reaction. In non-enzymatic glucose sensing, morphologically tunable copper oxide-based nanomaterials owned the high tunability of electrocatalytically active sites and intrinsic catalytic activity to meet efficient glucose electrooxidation for obtaining promoted non-enzymatic glucose sensing performances (sensitivity of 2331 µA mM-1 cm-2 and the limit of detection of 0.02 mM). In the supercapacitor, heterostructured Mn-Cu bimetallic oxide-based nanomaterials delivered abundant redox-active sites and continuous conductive network to optimize the synergistic effect of Mn and Cu redox species for boosting the pseudo-capacitance performance (areal capacitance value of 79.4 mF cm-2 at 0.2 mA cm-2 current density and capacitance retention of 74.9% after 1000 cycles). It concluded that morphologically tunable copper oxide-based nanomaterials on Cu wire with/without deposition of manganese oxide could be good candidates for the future design of synergistic multifunctional materials in electrochemical techniques.

FAK in Cancer: From Mechanisms to Therapeutic Strategies.

Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, is overexpressed and activated in many cancer types. FAK regulates diverse cellular processes, including growth factor signaling, cell cycle progression, cell survival, cell motility, angiogenesis, and the establishment of immunosuppressive tumor microenvironments through kinase-dependent and kinase-independent scaffolding functions in the cytoplasm and nucleus. Mounting evidence has indicated that targeting FAK, either alone or in combination with other agents, may represent a promising therapeutic strategy for various cancers. In this review, we summarize the mechanisms underlying FAK-mediated signaling networks during tumor development. We also summarize the recent progress of FAK-targeted small-molecule compounds for anticancer activity from preclinical and clinical evidence.

Comparison between the use of hypofractionated and conventionally fractionated radiotherapy in early breast cancer: A single-center real-world study in Taiwan.

BACKGROUND/PURPOSE: This study aimed to analyze the long-term outcomes of hypofractionated whole-breast irradiation (WBI) (HF-WBI) compared with those of conventionally fractionated WBI (CF-WBI) for early breast cancer treated with breast-conservation surgery (BCS) and adjuvant WBI in Taiwan. METHODS: This study included patients treated at our institution between 2012 and 2016. All patients with early breast cancer received BCS (pT1-2, pN0, M0) and adjuvant WBI through one of two treatment schemes. Propensity score matching analysis was conducted to create comparable cohorts. The major result is ipsilateral breast tumor recurrence (IBTR) rates and overall survival rates. RESULTS: A total of 869 patients with early-stage breast cancer received adjuvant HF-WBI or CF-WBI were included. After matching, 718 patients were separated into two groups of the same number. With a median follow-up of 66 months, seven cases of IBTR were noted (three for CF, four for HF). There were no significant differences between the HF-WBI and CF-WBI groups in 5-year IBTR rates (0.9% vs 0.6%, P = 0.3887, 95% CI [0.25-7.79]) and 5-year overall survival rates (98.1% vs 98.9%, P = 0.4702, 95% CI [0.32-3.49]). In our institution, the use of HF-WBI increased significantly from 5% before 2012 (Q3) to 92% in 2016 (Q4). There was no significant difference in grade 1-2 toxicity between the two treatment groups. Fewer cases of grade 3 skin toxicity noted in the HF-WBI group (zero vs four events). CONCLUSION: HF-WBI had similar IBTR, OS and toxicity to CF-WBI.

Synthesis of Bimetallic Ni-Co Phosphide Nanosheets for Electrochemical Non-Enzymatic H2O2 Sensing.

NiCoP nanosheets (NSs) were successfully synthesized using the hydrothermal and high-temperature phosphorization process. The obtained NiCoP NSs were immobilized on a glassy carbon electrode (GCE) and used to construct a novel sensing platform for electrochemical non-enzymatic H2O2 sensing. Physicochemical characteristics of NiCoP NSs were obtained by field-emission scanning electron microscopy (FESEM), field-emission transmission electron microscope (FETEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). In addition, the electrochemical properties of NiCoP NSs were obtained by cyclic voltammetry (CV) and chronoamperometry (CA) towards the non-enzymatic detection of H2O2. FESEM and FETEM images provided a morphological insight (the unique nanosheets morphology of NiCoP) that could expose more active sites to promote mass/charge transport at the electrode/electrolyte interface. XRD and XPS results also confirmed the crystalline nature of the NiCoP nanosheets and the coexistence of multiple transitional metal oxidation states in NiCoP nanosheets. These unique physicochemical characteristics had a degree of contribution to ensuring enhancement in the electrochemical behavior. As a result, the synthesized NiCoP NSs composed of intercalated nanosheets, as well as the synergistic interaction between bimetallic Ni/Co and P atoms exhibited excellent electrocatalytical activity towards H2O2 electroreduction at neutral medium. As the results showed, the electrochemical sensing based on NiCoP NSs displayed a linear range of 0.05~4 mM, a sensitivity of 225.7 µA mM-1 cm-2, a limit of detection (LOD) of 1.190 µM, and good selectivity. It was concluded that NiCoP NSs-based electrochemical sensing might open new opportunities for future construction of H2O2 sensing platforms.

Different Tyrosine Kinase Inhibitors Used in Treating EGFR-Mutant Pulmonary Adenocarcinoma with Brain Metastasis and Intracranial Intervention Have No Impact on Clinical Outcomes.

Brain metastasis in patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations is a factor of poor prognosis. We conducted a retrospective study to determine the optimal treatment strategy for EGFR-mutant NSCLC patients with brain metastasis receiving or not receiving intracranial intervention. A total of 186 patients treated with an EGFR TKI were enrolled in the study, and 79 (42%) received intracranial intervention. Patients who received intracranial intervention and those who did not had a similar treatment response rate (RR), progression-free survival (PFS) (median PFS: 11.0 vs. 10.0 months, p = 0.4842), and overall survival (OS) (median OS: 23.0 vs. 23.2 months, p = 0.2484). Patients treated with gefitinib, erlotinib, afatinib, or osimertinib had a similar RR (63%, 76%, 81%, or 100%, respectively, p = 0.1390), but they had significantly different PFS (median PFS: 7.5, 10.0, 14.8 months, or not reached, respectively, p = 0.0081). In addition, OS tended to be different between different EGFR TKI treatments (median OS of 19.2, 23.7, or 33.0 months for gefitinib, erlotinib, or afatinib treatments, respectively, p = 0.0834). Afatinib and osimertinib both demonstrated significantly longer PFS than gefitinib in a Cox regression model. Graded prognostic assessment (GPA) versions 2017 and 2022 stratified patients with different OS; patients with higher GPA index scores had significantly longer OS (p = 0.0368 and 0.0407 for version 2017 and 2022, respectively).

Extended Graphite Supported Flower-like MnO2 as Bifunctional Materials for Supercapacitors and Glucose Sensing.

A simple, efficient, and cost-effective extended graphite as a supporting platform further supported the MnO2 growth for the construction of hierarchical flower-like MnO2/extended graphite. MnO2/extended graphite exhibited an increase in sp2 carbon bonds in comparison with that of extended graphite. It can be expected to display better electrical conductivity and further promote electron/ion transport kinetics for boosting the electrochemical performance in supercapacitors and glucose sensing. In supercapacitors, MnO2/extended graphite delivered an areal capacitance value of 20.4 mF cm-2 at 0.25 mA cm-2 current densities and great cycling stability (capacitance retention of 83% after 1000 cycles). In glucose sensing, MnO2/extended graphite exhibited a good linear relationship in glucose concentration up to about 5 mM, sensitivity of 43 µA mM-1cm-2, and the limit of detection of 0.081 mM. It is further concluded that MnO2/extended graphite could be a good candidate for the future design of synergistic multifunctional materials in electrochemical techniques.

First-Line Anaplastic Lymphoma Kinase (ALK) Inhibitors for ALK-Positive Lung Cancer in Asian Populations: Systematic Review and Network Meta-Analysis.

Various anaplastic lymphoma kinase inhibitors (ALKIs) have been approved for first-line use in treating anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). To date, no head-to-head comparison of these newer generation ALKIs has been made, and different efficacies of ALKIs may present across ethnicity. This study aims to compare newer generation ALKIs for treatment efficacy in Asian groups using network meta-analysis. Phase II/III trials that enrolled treatment-naïve Asian ALK-rearranged NSCLC patients treated by ALKIs were included. Progression-free survival (PFS) and overall response rate (ORR) of each trial were extracted as indicators of drug efficacy. Surfaces under cumulative ranking curves (SUCRAs) were calculated as a numeric presentation of the overall ranking associated with each agent. After a systematic literature review, six phase III clinical trials were included. Our results showed that newer generation ALKIs, such as alectinib, brigatinib, ensartinib, and lorlatinib, all demonstrated superior efficacy to crizotinib. Among those, ensartinib exhibited the best overall SUCRA value and ranked first among all agents. According to our network meta-analysis, ensartinib may currently be the most effective first-line treatment for Asian patients with ALK-positive NSCLC. However, this conclusion needs further validation by a larger scale of clinical trials or posthoc analysis of Asian populations. Moreover, in our comparison, low-dose alectinib (300 mg twice daily) exhibited an efficacy profile similar to a higher dose regimen in Asian populations.

Construction of a Label-Free Electrochemical Immunosensor Based on Zn-Co-S/Graphene Nanocomposites for Carbohydrate Antigen 19-9 Detection.

Nanocomposites of the binary transition metal sulfide Zn-Co-S/graphene (Zn-Co-S@G) were synthesized through a one-step hydrothermal method. They may be useful in the construction of an electrochemical immunosensor for carbohydrate antigen 19-9 (CA19-9) detection. Zn-Co-S dot-like nanoparticles uniformly covered the surface of graphene to form an interconnected conductive network, ensuring strong interaction between transition metal sulfide and graphene, which can expose numerous electroactive sites leading to the improvement of the amplified electrochemical signal toward a direct reduction of H2O2. Thus, the construction of an electrochemical immunosensor using Zn-Co-S@G nanocomposites showed outstanding sensing properties for detecting CA19-9. The constructed electrochemical immunosensor exhibited a good linear relationship in the range of 6.3 U·mL-1-300 U·mL-1, with the limit of detection at 0.82 U·mL-1, which makes it a promising candidate for an electrochemical immunosensor.

Loss of Fis1 impairs proteostasis during skeletal muscle aging in Drosophila.

Increased levels of dysfunctional mitochondria within skeletal muscle are correlated with numerous age-related physiopathological conditions. Improving our understanding of the links between mitochondrial function and muscle proteostasis, and the role played by individual genes and regulatory networks, is essential to develop treatments for these conditions. One potential player is the mitochondrial outer membrane protein Fis1, a crucial fission factor heavily involved in mitochondrial dynamics in yeast but with an unknown role in higher-order organisms. By using Drosophila melanogaster as a model, we explored the effect of Fis1 mutations generated by transposon Minos-mediated integration. Mutants exhibited a higher ratio of damaged mitochondria with age as well as elevated reactive oxygen species levels compared with controls. This caused an increase in oxidative stress, resulting in large accumulations of ubiquitinated proteins, accelerated muscle function decline, and mitochondrial myopathies in young mutant flies. Ectopic expression of Fis1 isoforms was sufficient to suppress this phenotype. Loss of Fis1 led to unbalanced mitochondrial proteostasis within fly muscle, decreasing both flight capabilities and lifespan. Fis1 thus clearly plays a role in fly mitochondrial dynamics. Further investigations into the detailed function of Fis1 are necessary for exploring how mitochondrial function correlates with muscle health during aging.

Targeting Pin1 for Modulation of Cell Motility and Cancer Therapy.

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) specifically binds and isomerizes the phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif, which leads to changes in protein conformation and function. Pin1 is widely overexpressed in cancers and plays an important role in tumorigenesis. Mounting evidence has revealed that targeting Pin1 is a potential therapeutic approach for various cancers by inhibiting cell proliferation, reducing metastasis, and maintaining genome stability. In this review, we summarize the underlying mechanisms of Pin1-mediated upregulation of oncogenes and downregulation of tumor suppressors in cancer development. Furthermore, we also discuss the multiple roles of Pin1 in cancer hallmarks and examine Pin1 as a desirable pharmaceutical target for cancer therapy. We also summarize the recent progress of Pin1-targeted small-molecule compounds for anticancer activity.