Structural Designs and Mechanogating Mechanisms of the Mechanosensitive Piezo Channels.

The evolutionarily conserved Piezo channel family, including Piezo1 and Piezo2 in mammals, serves as versatile mechanotransducers in various cell types and consequently governs fundamental pathophysiological processes ranging from vascular development to the sense of gentle touch and tactile pain. Piezo1/2 possess a unique 38-transmembrane (TM) helix topology and form a homotrimeric propeller-shaped structure comprising a central ion-conducting pore and three peripheral mechanosensing blades. The unusually curved TM region of the three blades shapes a signature nano-bowl configuration with potential to generate large in-plane membrane area expansion, which might confer exquisite mechanosensitivity to Piezo channels. Here, we review the current understanding of Piezo channels with a particular focus on their unique structural designs and elegant mechanogating mechanisms.

Protein arginine methyltransferase-1 deficiency restrains depression-like behavior of mice by inhibiting inflammation and oxidative stress via Nrf-2.

Current evidence indicates that depression is accompanied by the activation of inflammatory response and oxidative stress. Protein arginine methyltransferase 1 (PRMT1) is a histone methyltransferase that methylates Arg3 on histone H4, playing crucial role in regulating various pathological processes. In the study, we attempted to explore the effects of PRMT1 on animal model with depression through a single administration of lipopolysaccharide (LPS). Our results indicated that PRMT1 knockout (PRMT1-/-) improved LPS-induced anxiety- and depressive-like behavior, along with up-regulated expression levels of brain-derived neurotrophic factor (BDNF) and PSD-95. Furthermore, PRMT1 deficiency significantly improved LPS-induced changes in dendritic spine density in the areas of prefrontal cortex (PFC), CA3 and dentate gyrus (DG), and nucleus accumbens (NAc). In addition, PRMT1 deletion ameliorated the neuroinflammatory responses, as evidenced by the reduced expression of interleukin 1ß (IL-1ß) and tumor necrosis factor (TNF)-α, which might be through repressing nuclear factor-κB (NF-κB) signaling. Moreover, oxidative stress induced by LPS was alleviated by PRMT1 knockout in hippocampus of mice at least partly via promoting Nrf-2 expressions. The anti-depressant effects of PRMT1 inhibition were verified in LPS-incubated astrocytes. Importantly, we found that PRMT1 knockout-alleviated inflammation and oxidative stress triggered by LPS were significantly recovered by the suppression of Nrf-2. Therefore, Nrf-2 was markedly involved in PRMT1-regulated depression-like behavior. Taken together, the results indicated that PRMT1 might be an important therapeutic target for developing effective treatment to prevent depressive-like behavior.

Design of foveated contact lens display for augmented reality.

We present a design of a contact lens display, which features an array of collimated light-emitting diodes and a contact lens, for the augmented reality. By building the infrastructure directly on top of the eye, eye is allowed to move or rotate freely without the need of exit pupil expansion nor eye tracking. The resolution of light-emitting diodes is foveated to match with the density of cones on the retina. In this manner, the total number of pixels as well as the latency of image processing can be significantly reduced. Based on the simulation, the device performance is quantitatively analyzed. For the real image, modulation transfer functions is 0.669757 at 30 cycle/degree, contrast ratio is 5, and distortion is 10%. For the virtual image, the field of view is 82°, best angular resolution is 0.38', modulation transfer function is above 0.999999 at 30 cycle/degree, contrast ratio is 4988, and distortion is 6%.

Exposure to an enriched environment promotes the terminal maturation and proliferation of natural killer cells in mice.

The maturation of natural killer (NK) cells is critical for the acquisition of robust effector functions and the immune response to tumors. However, the influence of psychological stress on NK-cell maturation remains unknown. In this study, we investigated the alteration of NK-cell maturation in response to enriched environment (EE) exposure, which induced eustress, or positive stress, in mice. Analysis of markers representing distinct mature stages revealed that EE promoted the terminal maturation of NK cells both centrally in the bone marrow and peripherally in the spleen and blood. Additionally, EE increased CD27+ immature and intermediate-mature NK cell proliferation in the bone marrow. Furthermore, EE exposure brought about a similar promoting effect on NK-cell maturation in tumor-bearing mice. In tumor-bearing mice, EE substantially enhanced the proliferative potential of splenic CD27+ NK cells compared to those in the bone marrow. EE-housed mice displayed a tumor-resistant phenotype and an increased proportion of intratumoral NK cells, especially CD11b+ CD27- mature NK cells, while splenectomy abolished the tumor-retardant effect caused by EE and EE-induced NK-cell infiltration into tumors. Given that our previous study demonstrated an important role for NK cells in EE-induced tumor inhibition, the findings of this study further indicate that the enhanced maturation and proliferation of splenic NK cells may contribute to EE-induced tumor inhibition to some extent. Taken together, the results of this study suggest a positive modulating effect of environment-induced eustress on NK-cell maturation, with potential implications for understanding how eustress boosts NK-cell antitumor immunity.

Simple strategy for sensitive detection of dopamine using CdTe QDs modified glassy carbon electrode.

BACKGROUND: Cellular and brain metabolism of dopamine can be correlated with a number of neurodegenerative disorders, our study was to explore a simple and efficient method to detect dopamine in real samples. METHODS: A new quantum dots (CdTe QDs) could be prepared using the hydrothermal method, the electrochemical biosensor was established by dropping CdTe QDs on the surface of glassy carbon electrode (GCE). RESULTS: The CdTe QDs/GCE exhibited the excellent electrochemical catalytic activity toward dopamine (DA) with good stability and high sensitivity in presence of interfering substances. The detection limit of DA was calculated by differential pulse voltammetry (DPV) as low as 0.3 µmol L-1 with a linear dynamic range of 1 µmol L-1 to 400 µmol L-1 . CONCLUSION: In this paper, the proposed electrochemical biosensor could be effectively used for the direct and rapid detection of DA in human serum and urine samples.

Preparation of quantum dots CdTe decorated graphene composite for sensitive detection of uric acid and dopamine.

The assembly of quantum dots (QDs) in a simply method opens up opportunities to obtain access to the full potential of assembled QDs by virtue of the collective properties of the ensembles. In this study, quantum dots CdTe and graphene (Gr) nanocomposite was constructed for the simultaneous determination of uric acid (UA) and dopamine (DA). The CdTe QDs-Gr nanocomposite was prepared by ultrasonication and was characterized with microscopic techniques. The nanocomposite modified electrode was characterized by cyclicvoltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Due to the synergistic effects between CdTe QDs and Gr, the fabricated electrode exhibited excellent electrochemical catalytic activities, good biological compatibility and high sensitivity toward the oxidation of UA and DA. Under optimum conditions, in the co-existence system the linear calibration plots for UA and DA were obtained over the range of 3-600 µM and 1-500 µM with detection limits of 1.0 µM and 0.33 µM. The fabricated biosensor also exhibits the excellent repeatability, reproducibility, storage stability along with acceptable selectivity.

[Effects of Ligustrazine Injection on Serum Cys C Level in Scierema Neonatorum Children Patients].

Objective To observe the effects of Ligustrazine Injection (LI) on serum cystatin C (Cys C) level in sclerema neonatorum (SN) children patients. Methods Totally 69 SN children patients were recrui- ted as the SN group, 39 with mild SN and 30 with moderate-severe SN. Another 30 neonates were recruited as a control group. Mild SN children patients and moderate-severe SN children patients were respectively assigned to the treatment group and the routine group according to random digit table. Children patients in the routine group received routine supportive treatment and symptomatic treatment, while those in the treatment group were additionally injected with LI (6 mg/kg, adding in 30 mL 5% glucose injection; once per day). All treatment lasted for 7 successive days. Serum level of Cys C, blood urea nitrogen (BUN) , and creatinine (Cr) were detected. The abnormality rate of Cys C, BUN, and Cr was respectively calculated, and their correlations analyzed. Meanwhile, scleroma subsidence time was observed in each group. Results The serum level of Cys C was obviously elevated more in the SN group than in the control group (t =10. 55, P <0. 01). There was no statistical difference in serum level of BUN or Cr between the control group and the SN group (t =1.50, 1. 73; P >0. 05). Serum Cys C level obviously increased in moderate-severe SN children patients than in mild SN children patients (t =2. 11 , P <0. 05); serum levels of BUN and Cr showed increasing tendency in moderate-severe SN children patients and mild SN children patients, but with no statistical difference (t =2. 07, 1. 92; P >0. 05). Linear correlation showed that serum Cys C level was respectively positively correlated with serum BUN level and serum Cr level in the SN group (r =0. 314,0. 287,P <0. 05). The abnormality rate of serum Cys C, BUN, and Cr was 72. 5% (50/69), 27. 5% (19/69), and 36. 2% (25/69), respectively. The abnormality rate of serum Cys C was significantly higher than that of BUN or Cr (x² =41. 04; P <0. 01). Compared with the routine group, serum Cys C level and scleroma subsidence time were obviously lowered in moderate-severe SN chil- dren patients and mild SN children patients of the treatment group (P <0. 05), but with no statistical difference in serum level of BUN or Cr (P >0. 05). Conclusions Serum Cys C level could reflect early renal injury in SN children patients. But LI could obviously reduce serum Cys C level, promote the recovery of renal injury of SN neonates, and shorten scleroma subsidence time.

Upregulation of miR-125b by estrogen protects against non-alcoholic fatty liver in female mice.

BACKGROUND & AIMS: Due to the protective effect of estrogen against hepatic fat accumulation, the prevalence of non-alcoholic fatty liver disease (NAFLD) in premenopausal women is lower than that in men at the same age and in postmenopausal women. Our study was to further elucidate an underlying mechanism by which estrogen prevents NAFLD from miRNA perspective in female mice. METHODS: miRNA expression was evaluated by TaqMan miRNA assay. Luciferase and ChIP assay were done to validate regulation of miR-125b by estrogen via estrogen receptor alpha (ERα). Nile red and Oil red O staining were used to check lipid content. Overexpressing or inhibiting the physiological role of miR-125b in the liver of mice through injecting adenovirus were used to identify the function of miR-125b in vivo. RESULTS: miR-125b expression was activated by estrogen via ERα in vitro and in vivo. miR-125b inhibited lipid accumulation both in HepG2 cells and primary mouse hepatocytes. Consistently, ovariectomized or liver-specific ERα knockdown mice treated with miR-125b overexpressing adenoviruses were resistant to hepatic steatosis induced by high-fat diet, due to decreased fatty acid uptake and synthesis and decreased triglyceride synthesis. Conversely, inhibiting the physiological role of miR-125b with a sponge decoy slightly promoted liver steatosis with a high-fat diet. Notably, we provided evidence showing that fatty acid synthase was a functional target of miR-125b. CONCLUSION: Our findings identify a novel mechanism by which estrogen protects against hepatic steatosis in female mice via upregulating miR-125b expression.

Invasive pneumococcal diseases in Chinese children: a multicentre hospital-based active surveillance from 2019 to 2021.

This study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of Streptococcus pneumoniae isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed. Serotypes, antibiotic susceptibility, and multi-locus sequence typing (MLST) of pneumococcal isolates were also detected. A total of 478 IPD cases and 355 pneumococcal isolates were enrolled. Among the patients, 260 were male, and the median age was 35 months (interquartile range, 12-46 months). Septicaemia (37.7%), meningitis (32.4%), and pneumonia (27.8%) were common disease types, and 46 (9.6%) patients died from IPD. Thirty-four serotypes were detected, 19F (24.2%), 14 (17.7%), 23F (14.9%), 6B (10.4%) and 19A (9.6%) were common serotypes. Pneumococcal isolates were highly resistant to macrolides (98.3%), tetracycline (94.1%), and trimethoprim/sulfamethoxazole (70.7%). Non-sensitive rates of penicillin were 6.2% and 83.3% in non-meningitis and meningitis isolates. 19F-ST271, 19A-ST320 and 14-ST876 showed high resistance to antibiotics. This multi-centre study reports the clinical features of IPD and demonstrates serotype distribution and antibiotic resistance of pneumococcal isolates in Chinese children. There exists the potential to reduce IPD by improved uptake of pneumococcal vaccination, and continued surveillance is warranted.

Tethering Piezo channels to the actin cytoskeleton for mechanogating via the cadherin-ß-catenin mechanotransduction complex.

The mechanically activated Piezo channel plays a versatile role in conferring mechanosensitivity to various cell types. However, how it incorporates its intrinsic mechanosensitivity and cellular components to effectively sense long-range mechanical perturbation across a cell remains elusive. Here we show that Piezo channels are biochemically and functionally tethered to the actin cytoskeleton via the cadherin-ß-catenin mechanotransduction complex, whose perturbation significantly impairs Piezo-mediated responses. Mechanistically, the adhesive extracellular domain of E-cadherin interacts with the cap domain of Piezo1, which controls the transmembrane gate, while its cytosolic tail might interact with the cytosolic domains of Piezo1, which are in close proximity to its intracellular gates, allowing a direct focus of adhesion-cytoskeleton-transmitted force for gating. Specific disruption of the intermolecular interactions prevents cytoskeleton-dependent gating of Piezo1. Thus, we propose a force-from-filament model to complement the previously suggested force-from-lipids model for mechanogating of Piezo channels, enabling them to serve as versatile and tunable mechanotransducers.

Preparation of chitosan-cellulose-benzyl isothiocyanate nanocomposite film for food packaging applications.

To improve the mechanical and barrier properties of cellulose and chitosan (CS) and to allow the application of volatile antibacterial benzyl isothiocyanate (BITC) in active packaging, a double-layer nanocomposite film was prepared. Cellulose nanofibers (CNF) were crosslinked with CS via genipin to build the substrate. Quaternized cellulose nanocrystals (QCNC) were synthesized for carrying BITC as the coating material. By the layer-by-layer self-assembly approach, CS-CNF/QCNC-BITC film was fabricated. This film possessed the tensile strength of 33.75 MPa, low permeabilities of oxygen (6.9 × 10-17 m3/s·m·Pa) and moisture (1.2 × 10-11 g/s·m·Pa), and good antibacterial activity with the inhibition zone diameters of 4.9, 4.2 and 2.7 cm against Escherichia coli, Salmonella typhimurium and Staphylococcus aureus. The total viable count, total volatile basic nitrogen and thiobarbituric acid-reactive substances of the chicken wrapped CS-CNF/QCNC-BITC were only 4.4 log CFU/g, 17.7 mg/100 g and 0.44 mg/kg at 14 days, indicating a potential application of CS-CNF/QCNC-BITC for food packaging.

Astrocytic Piezo1-mediated mechanotransduction determines adult neurogenesis and cognitive functions.

Adult brain activities are generally believed to be dominated by chemical and electrical transduction mechanisms. However, the importance of mechanotransduction mediated by mechano-gated ion channels in brain functions is less appreciated. Here, we show that the mechano-gated Piezo1 channel is expressed in the exploratory processes of astrocytes and utilizes its mechanosensitivity to mediate mechanically evoked Ca2+ responses and ATP release, establishing Piezo1-mediated mechano-chemo transduction in astrocytes. Piezo1 deletion in astrocytes causes a striking reduction of hippocampal volume and brain weight and severely impaired (but ATP-rescuable) adult neurogenesis in vivo, and it abolishes ATP-dependent potentiation of neural stem cell (NSC) proliferation in vitro. Piezo1-deficient mice show impaired hippocampal long-term potentiation (LTP) and learning and memory behaviors. By contrast, overexpression of Piezo1 in astrocytes sufficiently enhances mechanotransduction, LTP, and learning and memory performance. Thus, astrocytes utilize Piezo1-mediated mechanotransduction mechanisms to robustly regulate adult neurogenesis and cognitive functions, conceptually highlighting the importance of mechanotransduction in brain structure and function.

Epidemiology of Cardiopulmonary Arrest and Outcome of Resuscitation in PICU Across China: A Prospective Multicenter Cohort Study.

Objective: To investigate the epidemiology and the effectiveness of resuscitation from cardiopulmonary arrest (CPA) among critically ill children and adolescents during pediatric intensive care unit (PICU) stay across China. Methods: A prospective multicenter study was conducted in 11 PICUs in tertiary hospitals. Consecutively hospitalized critically ill children, from 29-day old to 18-year old, who had suffered from CPA and required cardiopulmonary resuscitation (CPR) in the PICU were enrolled (December 2017-October 2018). Data were collected and analyzed using the "in-hospital Utstein style." Neurological outcome was assessed with the Pediatric Cerebral Performance Category (PCPC) scale among children who had survived. Factors associated with the return of spontaneous circulation (ROSC) and survival at discharge were evaluated using multivariate logistic regression. Results: Among 11,599 admissions to PICU, 372 children (3.2%) had CPA during their stay; 281 (75.5%) received CPR, and 91 (24.5%) did not (due to an order of "Do Not Resuscitate" requested by their guardians). Cardiopulmonary disease was the most common reason for CPA (28.1% respiratory and 19.6% circulatory). The most frequent initial dysrhythmia was bradycardia (79%). In total, 170 (60.3%) of the total children had an ROSC, 91 had (37.4%) survived till hospital discharge, 28 (11.5%) had survived 6 months, and 19 (7.8%) had survived for 1 year after discharge. Among the 91 children who were viable at discharge, 47.2% (43/91) received a good PCPC score (1-3). The regression analysis results revealed that the duration of CPR and the dose of epinephrine were significantly associated with ROSC, while the duration of CPR, number of CPR attempts, ventricular tachycardia/ventricular fibrillation (VT/VF), and the dose of epinephrine were significantly associated with survival at discharge. Conclusion: The prevalence of CPA in critically ill children and adolescents is relatively high in China. The duration of CPR and the dose of epinephrine are associated with ROSC. The long-term prognosis of children who had survived after CPR needs further improvement.

TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells.

TMEM120A, a member of the transmembrane protein 120 (TMEM120) family, has a pivotal function in adipocyte differentiation and metabolism, and may also contribute to sensing mechanical pain by functioning as an ion channel named TACAN. Here we report that expression of TMEM120A is not sufficient in mediating poking- or stretch-induced currents in cells and have solved cryo-electron microscopy (cryo-EM) structures of human TMEM120A (HsTMEM120A) in complex with an endogenous metabolic cofactor (coenzyme A, CoASH) and in the apo form. HsTMEM120A forms a symmetrical homodimer with each monomer containing an amino-terminal coiled-coil motif followed by a transmembrane domain with six membrane-spanning helices. Within the transmembrane domain, a CoASH molecule is hosted in a deep cavity and forms specific interactions with nearby amino acid residues. Mutation of a central tryptophan residue involved in binding CoASH dramatically reduced the binding affinity of HsTMEM120A with CoASH. HsTMEM120A exhibits distinct conformations at the states with or without CoASH bound. Our results suggest that TMEM120A may have alternative functional roles potentially involved in CoASH transport, sensing, or metabolism.

Antibacterial Activity and Potential Application in Food Packaging of Peptides Derived from Turbot Viscera Hydrolysate.

As a good choice for food preservation, antimicrobial peptides (AMPs) have received much attention in recent years. In this paper, peptides derived from the turbot viscera hydrolysate were identified by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS), and the physicochemical properties and structural characteristics were analyzed by in silico tools. Furthermore, three cationic peptides with potential hydrophobicity and amphipathy were synthesized; their cytotoxicity, hemolysis, and antibacterial activities were investigated. In particular, Sm-A1 (GITDLRGMLKRLKKMK), a peptide with 16 amino acids, showed an outstanding antibacterial activity against both Gram-positive and Gram-negative bacteria by damaging the cell membrane integrity. Moreover, Sm-A1 was successfully loaded into hydroxyl-rich poly(vinyl alcohol) (PVA)/chitosan (CS) hydrogel to improve the antibacterial activity and biofilm inhibition effect. PVA/CS+7.5‰ Sm-A1 hydrogel can satisfactorily protect the salmon muscle from the microbiological contamination and texture deterioration.

Electrochemical strategy with zeolitic imidazolate framework-8 and ordered mesoporous carbon for detection of xanthine.

An accurate, safe, environmentally friendly, fast and sensitive electrochemical biosensors were developed to detect xanthine in serum. The metal-organic framework ZIF-8 was synthesised and elemental gold was supported on the surface of ZIF-8 by reduction method to synthesise Ag-ZIF-8. The mesoporous carbon material and the synthesised Ag-ZIF-8 were, respectively, applied to a glassy carbon electrode to construct biosensors. The constructed biosensor has a good linear relation in the range of 1-280 µmol l-1 of xanthine and the detection limit is 0.167 µmol l-1. The relative standard deviation value in serum samples was <5%, and the recoveries were 96-106%, indicating the good selectivity, stability and reproducibility of this electrochemical biosensor.

Adiponectin Suppresses Human Pancreatic Cancer Growth through Attenuating the ß-Catenin Signaling Pathway.

Adipokines are emerging as a link between obesity and obesity-related cancers, including pancreatic cancer. Adiponectin is an abundant adipokine with pleiotropic beneficial roles in metabolic disorders. Low adiponectin levels are commonly observed in human obesity and have been associated with increased pancreatic cancer risk in prospective epidemiologic studies. Here, we investigated the direct effect of adiponectin on human pancreatic cancer in vitro and in vivo. Our results showed that adiponectin treatment significantly inhibited the proliferation of human pancreatic cancer cells. Knockdown of adiponectin receptors completely eliminated the antiproliferation effect of adiponectin and markedly promoted the growth of human pancreatic cancer xenografts in nude mice. Further analysis revealed that adiponectin blocked the phosphorylation/inactivation of GSK-3ß, suppressed the intracellular accumulation of ß-catenin, reduced the expression of cyclin D1, and consequently caused cell cycle accumulation at the G0-G1 phase in pancreatic cancer cells. Adiponectin-mediated attenuation of cell proliferation was abrogated by the GSK-3ß inhibitor. In addition, a microarray analysis revealed that adiponectin also downregulated the expression of TCF7L2, a coactivator of ß-catenin, at the transcriptional level in pancreatic cancer cells. These results indicated that the protective role of adiponectin against human pancreatic cancer might be attributed to its attenuating effect on the ß-catenin signaling pathway. Taken together, our findings support a causal link between hypoadiponectinemia and increased pancreatic cancer risk, and suggest that activating adiponectin signaling could be a novel therapeutic strategy for obesity-related pancreatic cancer.

Implantable sandwich PHBHHx film for burst-free controlled delivery of thymopentin peptide.

Sustained release and non-parental formulations of peptides and protein drugs are highly desirable because of enhanced therapeutic effects as well as improved patient compliance. This is especially true for small peptides such as thymopentin (TP5). To this end, implantable sandwich poly (hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) films were designed to prolong release time and to inhibit burst release phenomenon of TP5 by a simple volatilization method. In vitro release studies revealed that sandwich films had nearly no burst release. In vivo release time of sandwich films was prolonged to 42 days. Pharmacodynamic evaluation demonstrated that TP5 sandwich films significantly increased survival rates in a rat immunosuppressive model and normalized CD4+/CD8+ values. These results suggest that TP5 released from sandwich films can attenuate cyclophosphamide's immunosuppressive activity, and possibly achieve results comparable to daily TP5 injection therapy. Thus, sandwich PHBHHx films show excellent potential as a sustained, burst-free release system for small molecular weight, hydrophilic peptide drugs.

Meta-analysis of SIRT1 expression as a prognostic marker for overall survival in gastrointestinal cancer.

Sirtuin 1 (SIRT1), a well-characterized NAD+-dependent histone deacetylase, is generally up-regulated in gastrointestinal cancers. However, the prognostic value of SIRT1 in gastrointestinal cancer remains inconclusive. Therefore, we report a meta-analysis of the association of SIRT1 expression with overall survival (OS) in gastrointestinal cancer. PubMed was systematically searched for studies evaluating the expression of SIRT1 and OS in patients with gastrointestinal cancer. Fifteen studies (six evaluating colorectal cancer, three evaluating hepatocellular carcinoma, three evaluating gastric cancer, and one each evaluating pancreatic cancer, esophageal squamous cell carcinoma, and gastroesophageal junction cancer) with 3,024 patients were finally included. The median percentage of gastrointestinal cancers with high SIRT1 expression was 52.5%. Overall analysis showed an association between high SIRT1 expression and worse OS [summary hazard ratio (sHR) 1.54, 95% confidence intervals (CI) 1.21-1.96] in gastrointestinal cancer. However, heterogeneity was observed across studies, which was mainly attributed to cancer type. Subgroup analysis revealed that SIRT1 was significantly associated with worse OS in non-colorectal gastrointestinal cancer (sHR 1.82, 95% CI 1.50-2.21), in particular in gastric cancer (sHR 3.19, 95% CI 1.97-5.16) and hepatocellular carcinoma (sHR 1.53, 95% CI 1.16-2.01), with no evidence of heterogeneity or bias. However, no association was observed in colorectal cancer (sHR 1.15, 95% CI 0.81-1.62). In conclusion, high SIRT1 expression is a potential marker for poor survival in non-colorectal gastrointestinal cancer, but not in colorectal cancer.

A Label-Free Electrochemical Biosensor Based on a Reduced Graphene Oxide and Indole-5-Carboxylic Acid Nanocomposite for the Detection of Klebsiella pneumoniae.

A label-free DNA hybridization electrochemical sensor for the detection of Klebsiella pneumoniae was developed, which could be helpful in the diagnosis of bacterial infections. Indole-5-carboxylic acid (ICA) and graphene oxide (GO) were electrodeposited on a glassy carbon electrode, and the resulting reduced GO (rGO)-ICA hybrid film served as a platform for immobilizing oligonucleotides on a single-stranded DNA (ssDNA) sequence. The conditions were optimized, with excellent electrochemical performance. A significant change was observed after hybridization of ssDNA with the target probe under optimum conditions. Hybridization with complementary, noncomplementary, one-base mismatched, and three-base mismatched DNA targets was studied effectively by differential pulse voltammetry. The proposed strategy could detect target DNA down to 3 × 10-11 M, with a linear range from 1 × 10-6 M to 1 × 10-10 M, showing high sensitivity. This electrochemical method is simple, free from indicator, and shows good selectivity. Hence, electrochemical biosensors are successfully demonstrated for the detection of K. pneumoniae.