Bridging Ionic Current Rectification and Resistive-Pulse Sensing for Reliable Wide-Linearity Detection.

As two mainstream ionic detection techniques, ionic current rectification (ICR) suffers from large fluctuations in trace level detection, while resistive-pulse sensing (RPS) encounters easy clogs in high-concentration detection. By rationally matching the nanopore size with the DNA tetrahedron (TDN), this work bridges the two techniques to achieve reliable detection with wide linearity. As a representative analyte, miRNA-10b could specifically combine with and release TDN from the interior wall, which thus induced the simultaneous generation of distinct ICR and RPS signals. The ICR signals could be attributed to the balance between the effective orifice and surface charge density of the inner wall, while the RPS signals were induced by the complex of miRNA-10b and TDN passing through the nanopore. Such an operation contributed to a wide detection range of 1 fM-1 nM with a good linearity. The feasibility of this method is also validated in single-cell and real plasma detection.

High-Precision Single-Cell microRNA Therapy by a Functional Nanopipette with Sensitive Photoelectrochemical Feedback.

This work proposes the concept of single-cell microRNA (miR) therapy and proof-of-concept by engineering a nanopipette for high-precision miR-21-targeted therapy in a single HeLa cell with sensitive photoelectrochemical (PEC) feedback. Targeting the representative oncogenic miR-21, the as-functionalized nanopipette permits direct intracellular drug administration with precisely controllable dosages, and the corresponding therapeutic effects can be sensitively transduced by a PEC sensing interface that selectively responds to the indicator level of cytosolic caspase-3. The experimental results reveal that injection of ca. 4.4 × 10-20 mol miR-21 inhibitor, i.e., 26488 copies, can cause the obvious therapeutic action in the targeted cell. This work features a solution to obtain the accurate knowledge of how a certain miR-drug with specific dosages treats the cells and thus provides an insight into futuristic high-precision clinical miR therapy using personalized medicine, provided that the prerequisite single-cell experiments are courses of personalized customization.

θ-Nanopipette for Single-Cell Resistive-Pulse Profiling of DNA Repair Proteins Accompanied by Drug Evaluation.

Single-cell analysis of the DNA repair protein is important but remains unachieved. Exploration of nanopipettte technologies in single-cell electroanalysis has recently seen rapid growth, while the θ-nanopipette represents an emerging technological frontier with its potential largely veiled. Here a θ-nanopipette is first applied for single-cell resistive-pulse sensing (RPS) of the important DNA repair protein O6-alkylguanine DNA alkyltransferase (hAGT). The removal of alkyl mutations by hAGT could restore the damaged aptamer linking with a structural DNA carrier, allowing the selective binding of the aptamer to thrombin with precisely matched size to produce distinct RPS signals when passing through the orifice. Kinetic analysis of hAGT repair was studied. Meanwhile, the device shows the simultaneous on-demand infusion of inhibitors to inactivate the hAGT activity, indicative of its potential in drug screening for enhanced chemotherapy. This work provides a new paradigm for θ-nanopipette-based single-cell RPS of a DNA repair protein accompanied by drug evaluation.

Effects of probiotics in patients with morbid obesity undergoing bariatric surgery: a systematic review and meta-analysis.

BACKGROUND: Probiotics are commonly used after bariatric surgery. However, uncertainty remains regarding their effects. The purpose of this systematic review was to assess the effect of probiotics in patients with morbid obesity undergoing bariatric surgery. METHODS: PubMed, Cochrane Library, Embase, Science Direct, and Web of Science were searched from inception to April 4, 2023. No language restrictions were applied. Relevant randomized controlled trials and controlled clinical trials were included. We used the aggregated data extracted from the trials and assessed the heterogeneity. When severe heterogeneity was detected, a random effect model was used. All stages of the review were done by independent authors. RESULTS: We screened 2024 references and included 11 randomized controlled trials and controlled clinical trials. Compared with the protocol groups, probiotics showed significant effects on regulating aspartate amino transferase level (MD = -4.32 U/L; 95% CI [-7.10, -1.53], p = 0.002), triglycerides (MD = -20.16 mg/dL; 95% CI [-34.51, -5.82], p = 0.006), weight (MD = -1.99 kg; 95% CI [-3.97, -0.01], p = 0.05), vitamin B12 (MD = 2.24 pg/dL; 95% CI [-0.02, 4.51], p = 0.05), dietary energy (MD = -151.03 kcal; 95% CI [-215.68, -86.37], p < 0.00001), dietary protein (MD = -4.48 g/day, 95% CI [-8.76, -0.20], p = 0.04), dietary carbohydrate (MD = -34.25 g/day, 95% CI [-44.87, -23.62], p < 0.00001), and dietary fiber (MD = -2.17 g/day, 95% CI [-3.21, -1.14], p < 0.0001). There were no severe side effects related to probiotics. CONCLUSIONS: Our meta-analysis suggested that probiotics may delay the progression of liver function injury, improve lipid metabolism, reduce weight, and reduce food intake, although the effects on other indicators were insignificant. Probiotics may be helpful for patients undergoing bariatric surgery. The review was registered on PROSPERO (International prospective register of systematic reviews): CRD42023407970. No primary source of funding.

Mitochondrial metabolic dysfunction and non-alcoholic fatty liver disease: new insights from pathogenic mechanisms to clinically targeted therapy.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is among the most widespread metabolic disease globally, and its associated complications including insulin resistance and diabetes have become threatening conditions for human health. Previous studies on non-alcoholic fatty liver disease (NAFLD) were focused on the liver's lipid metabolism. However, growing evidence suggests that mitochondrial metabolism is involved in the pathogenesis of NAFLD to varying degrees in several ways, for instance in cellular division, oxidative stress, autophagy, and mitochondrial quality control. Ultimately, liver function gradually declines as a result of mitochondrial dysfunction. The liver is unable to transfer the excess lipid droplets outside the liver. Therefore, how to regulate hepatic mitochondrial function to treat NAFLD has become the focus of current research. This review provides details about the intrinsic link of NAFLD with mitochondrial metabolism and the mechanisms by which mitochondrial dysfunctions contribute to NAFLD progression. Given the crucial role of mitochondrial metabolism in NAFLD progression, the application potential of multiple mitochondrial function improvement modalities (including physical exercise, diabetic medications, small molecule agonists targeting Sirt3, and mitochondria-specific antioxidants) in the treatment of NAFLD was evaluated hoping to provide new insights into NAFLD treatment.

CXCR5+ CD8+ T cells potently infiltrate pancreatic tumors and present high functionality.

Despite continued improvement in conventional therapy, pancreatic cancer continues to be one of the deadliest tumors worldwide with abysmal 5-year survival rate. New immunotherapeutic strategies that aim at improving antitumor cytotoxic CD8+ T cell responses are being developed in solid tumors. To assist the development of immunotherapies, we investigated the CD8+ T cells in pancreatic cancer patients. Compared to healthy individuals, pancreatic cancer patients presented a significant enrichment in the frequency of CD8+CXCR5+ T cells. In the tumor microenvironment, the frequencies of CD8+CXCR5+ T cells were further increased. In most cases, over half of tumor-infiltrating CD8+ T cells were CD8+CXCR5+ T cells. Compared to the circulating population, the tumor-infiltrating CD8+CXCR5+ T cells expressed higher levels of PD-1 and TIM-3. Functional analyses demonstrated that upon CD3/CD28 activation, the percentages of TNF-expressing and IFN-γ-expressing cells in CD8+CXCR5+ T cells were significantly higher than that in CD8+CXCR5- T cells. CD8+CXCR5+ T cells also presented enhanced cytotoxicity than CD8+CXCR5- T cells. Upon PD-1 and TIM-3 blockade, the functions of CD8+CXCR5+ T cells were further improved. The disease-free survival of pancreatic cancer patients following tumor resection was positively correlated with the frequencies of circulating and tumor-infiltrating CD8+CXCR5+ T cells. Together, our study identified that CD8+CXCR5+ T cells were a potent subset of CD8+ T cells that were highly enriched in pancreatic cancer patients and could respond to anti-PD-1/anti-TIM-3 blockade by further upregulation in function.

A three-in-one point-of-care electrochemical sensing platform for accurate monitoring of diabetes.

A three-in-one electrochemical sensing platform was designed for the simultaneous detection of total hemoglobin (tHb), glycated hemoglobin (HbA1c) and HbA1c% by using a dual-aptamer sensing strategy. The developed sensing platform exhibits excellent sensitivity, selectivity, repeatability and long-term stability, and holds promising prospects in the early diagnosis and long-term monitoring of diabetes.

Cellular senescence and metabolic reprogramming: Unraveling the intricate crosstalk in the immunosuppressive tumor microenvironment.

The intrinsic oncogenic mechanisms and properties of the tumor microenvironment (TME) have been extensively investigated. Primary features of the TME include metabolic reprogramming, hypoxia, chronic inflammation, and tumor immunosuppression. Previous studies suggest that senescence-associated secretory phenotypes that mediate intercellular information exchange play a role in the dynamic evolution of the TME. Specifically, hypoxic adaptation, metabolic dysregulation, and phenotypic shifts in immune cells regulated by cellular senescence synergistically contribute to the development of an immunosuppressive microenvironment and chronic inflammation, thereby promoting the progression of tumor events. This review provides a comprehensive summary of the processes by which cellular senescence regulates the dynamic evolution of the tumor-adapted TME, with focus on the complex mechanisms underlying the relationship between senescence and changes in the biological functions of tumor cells. The available findings suggest that components of the TME collectively contribute to the progression of tumor events. The potential applications and challenges of targeted cellular senescence-based and combination therapies in clinical settings are further discussed within the context of advancing cellular senescence-related research.

Current evidence on the relationship between SNP309 polymorphism in the MDM2 gene and colorectal cancer risk.

It has been demonstrated that MDM2 is a well-established negative regulator of the p53 protein and might be associated with a significantly earlier age of onset of several tumors, including colorectal cancer (CRC). In recent years, a T to G substitution (SNP309) in the promoter of MDM2 has been extensively studied as a potential CRC risk factor; however, the results are inconsistent. To derive a more precise estimation of association between MDM2 SNP309 polymorphism and CRC risk, we conducted a meta-analysis of 11 studies with 4,050 CRC cases and 3,688 controls. For MDM2 SNP309 polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis. In the subgroup analyses by ethnicity, source of controls, and Hardy-Weinberg equilibrium (HWE) in controls, a significantly increased risk was observed among Asians (heterozygous model: odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.06-1.39, P = 0.005), population-based studies (heterozygous model: OR = 1.17, 95% CI = 1.02-1.34, P = 0.027), and among studies without the HWE (recessive model: OR = 1.42, 95% CI = 1.03-1.94, P = 0.030). When excluding three studies deviated from HWE, the significant results were also observed for heterozygous model in overall population (OR = 1.16, 95% CI = 1.02-1.31, P = 0.020). No publication bias was found in the present study. In conclusion, this meta-analysis suggests that MDM2 SNP309 polymorphism was associated with CRC susceptibility, especially among Asians. Further research is needed to assess possible gene-gene or gene-environment-lifestyle interactions on CRC.

Expression, immunolocalization, and serological reactivity of a novel sphingomyelin phosphodiesterase-like protein, an excretory/secretory antigen from Clonorchis sinensis.

Clonorchiasis, caused by Clonorchis sinensis infection, is a zoonotic parasitic disease of hepatobiliary system in which the proteins released by adult are major pathogenetic factors. In this study, we first characterized a putative sphingomyelin phosphodiesterase (CsSMPase) A-like secretory protein, which was highly expressed in the adult worm. The full-length gene was cloned. The putative protein is of relatively low homology comparing with SMPase from other species, and of rich T cell and B cell epitopes, suggesting that it is an antigen of strong antigenicity. The complete coding sequence of the gene was expressed in the Escherichia coli. The recombinant CsSMPase (rCsSMPase) can be recognized by C. sinensis-infected serum, and the protein immunoserum can recognize a specific band in excretory/secretory products (ESPs) of C. sinensis adult by western blotting. Immunolocalization revealed that CsSMPase was not only localized on tegument, ventral sucker of metacercaria, and the intestine of adult but also on the nearby epithelium of bile duct of the infected Sprague-Dawley rats, implying that CsSMPase was mainly secreted and excreted through adult intestine and directly interacted with bile duct epithelium. Although immunized rats evoked high level antibody response, the antigen level was low in clonorchiasis patients. And the sensitivity and specificity of rCsSMPase were 50.0 % (12/24) and 88.4 % (61/69), in sera IgG-ELISA, respectively. It is likely due to the fact that CsSMPase binding to the plasma membrane of biliary epithelium decreases the antigen immune stimulation.

[Characteristics of Silent Alpha Thalassemia Gene in Child-Bearing Adults in Guangdong].

OBJECTIVE: To investigate characteristics of silent alpha thalassemia genes in child-bearing adults in Guangdong, in order to provide data for the prevention and control of hemoglobin H disease. METHODS: A total of 8 752 cases were collected from January 2016 to December 2020. Gap-PCR was used to detect the deletional of α-thalassemia mutations (-α3.7, -α4.2), while PCR reverse dot blot hybridization assay (RDB) was used to detect the non-deletional α-thalassemia mutations (Hb CS, Hb QS and Hb Westmead). RESULTS: Among 8 752 subjects, 717 cases of silent α-thalassemia were detected, the detection rate was 8.19%, including 555 cases of deletional α-thalassemia (77.41%) and 162 cases of non-deletional α-thalassemia 22.59%. The mean corpuscular volume (MCV) of deletional silent α-thalassemia was (82.09±4.10) fl, and mean corpuscular hemoglobin (MCH) was (27.03±1.37) pg, which both were over the diagnostic cut-off value for thalassemia. The MCV of non-deletional silent α-thalassemia was (81.07±4.93) fl, and MCH was (26.77±2.20) pg. According to the diagnostic criteria, if using MCV<82 fl or (and) MCH<27 pg as a positive criteria for screening thalassemia in the childbearing age, the screening sensitivity was 53.14% and different in different genotype, among which ααQS/αα was 100%, -α3.7/αα, -α4.2/αα, ααCS/αα and ααWS/αα was 62.15%, 63.41%, 44.83% and 39.62%, respectively. Namely, nearly half the carriers of such mutations might have escaped detection as a result of their screening strategy. CONCLUSION: When a couple is preparing for pregnancy, if one of them has been determined to be mild α-thalassemia or hemoglobin H disease, other half is necessary to carry out silent α thalassemia detection to prevent the birth of children with hemoglobin H disease even if MCV>82 fl and MCH>27 pg.

Fluid evolution and related fluid-rock interactions of the Oligocene Zhuhai sandstones in the Baiyun Sag, northern margin of the South China Sea.

Pore fluids control the diagenetic processes and storage spaces of deep clastic rock reservoirs and have become a major area of interest within the fields of sedimentology and petroleum geology. This paper aims to relate the diagenetic processes of the Oligocene Zhuhai sandstones in the Baiyun Sag to pore fluids varying with burial depth. The types and distribution patterns of authigenic minerals are investigated through analysis of petrographic, mineralogical, and geochemical features to illustrate the origin and flow patterns of pore fluids and their influences on reservoir diagenesis. Strong cementation of eogenetic carbonate cement near the sandstone-mudstone interface was a consequence of material migration from adjacent mudstones on a large scale. The pore fluids were mainly affected by microbial methanogenesis and carbonate mineral dissolution in adjacent mudstones during eogenesis. The pore fluids were diffusively transported in a relatively open geochemical system within a local range. Support for this model is provided by the heavier stable isotopic values present in eogenetic calcite and dolomite. Feldspar dissolution during early mesogenesis was spatially accompanied by the precipitation of authigenic quartz and ferroan carbonate cement. Pore fluids in this period were rich in organic acids and CO2, and their migration mechanism was diffusive transport. The obviously lighter carbon and oxygen isotopic compositions of the ferroan calcite support this inference. During late mesogenesis, the input of deep hydrothermal fluid might have been partly responsible for the precipitation of ankerite, barite and authigenic albite. Oil charging may have inhibited carbonate cementation and compaction, accordingly preserving porosity, and together with authigenic kaolinite, might have promoted the transition of the reservoir from water wet to oil wet to the benefit of oil entrapment. The findings reported here shed new light on the evaluation and prediction of sandstone reservoirs that have experienced multiple periods of fluid flow.

New insights into the characteristics of DRAK2 and its role in apoptosis: From molecular mechanisms to clinically applied potential.

As a member of the death-associated protein kinase (DAPK) family, DAP kinase-associated apoptosis-inducing kinase 2 (DRAK2) performs apoptosis-related functions. Compelling evidence suggests that DRAK2 is involved in regulating the activation of T lymphocytes as well as pancreatic ß-cell apoptosis in type I diabetes. In addition, DRAK2 has been shown to be involved in the development of related tumor and non-tumor diseases through a variety of mechanisms, including exacerbation of alcoholic fatty liver disease (NAFLD) through SRSF6-associated RNA selective splicing mechanism, regulation of chronic lymphocytic leukemia and acute myeloid leukemia, and progression of colorectal cancer. This review focuses on the structure, function, and upstream pathways of DRAK2 and discusses the potential and challenges associated with the clinical application of DRAK2-based small-molecule inhibitors, with the aim of advancing DRAK2 research.

Molybdenum Disulfide-Based Nanoprobes: Preparation and Sensing Application.

The use of nanoprobes in sensors is a popular way to amplify their analytical performance. Coupled with two-dimensional nanomaterials, nanoprobes have been widely used to construct fluorescence, electrochemical, electrochemiluminescence (ECL), colorimetric, surface enhanced Raman scattering (SERS) and surface plasmon resonance (SPR) sensors for target molecules' detection due to their extraordinary signal amplification effect. The MoS2 nanosheet is an emerging layered nanomaterial with excellent chemical and physical properties, which has been considered as an ideal supporting substrate to design nanoprobes for the construction of sensors. Herein, the development and application of molybdenum disulfide (MoS2)-based nanoprobes is reviewed. First, the preparation principle of MoS2-based nanoprobes was introduced. Second, the sensing application of MoS2-based nanoprobes was summarized. Finally, the prospect and challenge of MoS2-based nanoprobes in future were discussed.

Translocation of Specific DNA Nanocarrier through an Ultrasmall Nanopipette: Toward Single-Protein-Molecule Detection with Superior Signal-to-Noise Ratio.

The use of functional DNA nanostructures as carriers to ship proteins through solid-state nanopores has recently seen substantial growth in single-protein-molecule detection (SPMD), driven by the potential of this methodology and implementations that it may enable. Ultrasmall nanopores have exhibited obvious advantages in spatiotemporal biological detection due to the appropriate nanoconfined spaces and unique properties. Herein, a 6.8 nm DNA tetrahedron (TDN) with a target-specific DNA aptamer (TDN-apt) was engineered to carry the representative target of acetylcholinesterase (AChE) through an ultrasmall nanopipet with a 30 nm orifice, underpinning the advanced SPMD of AChE with good performance in terms of high selectivity, low detection limit (0.1 fM), and especially superior signal-to-noise ratio (SNR). The kinetic interaction between TDN-apt and AChE was studied and the practical applicability of the as-developed SPMD toward real samples was validated using serum samples from patients with Alzheimer's disease. This work not only presented a feasible SPMD solution toward low-abundance proteins in complex samples and but also was envisioned to inspire more interest in the design and implementation of synergized DNA nanostructure-ultrasmall nanopore systems for future SPMD development.

Sensitive detection of telomerase activity in cells using a DNA-based fluorescence resonance energy transfer nanoprobe.

Telomerase activity is inhibited in normal somatic cells but abnormally high in the majority of cancer cells. Maintenance of active telomerase in cancer cells promotes proliferation and immortalization. With the difference in telomerase activity between cancer and normal cells in mind, we designed a nanoprobe based on quantum dot (QD) and fluorescence resonance energy transfer (FRET). The nanoprobe consisted of a specific sequence of DNA with the two ends labeled with QD as a fluorescent donor and Alexa488 as a fluorescent acceptor, respectively. FRET signal tracking was performed by adjusting the distance between donors and acceptors, and changes in the FRET signal shown to be related to telomerase activity. Incubation of cells with the nanoprobe facilitated sensing of intracellular telomerase activity, and consequent discrimination between normal and cancer cells. Our novel DNA nanoprobe based on QD-FRET achieved sensitive detection of telomerase in cells up to a detection limit of one cell, and quantitative detection of telomerase activity in different numbers of cells. The nanoprobe generated in this study is expected to allow dynamically monitoring of the changes in telomerase activity in cells under treatment with drugs, providing a potential basis for early diagnosis and management of cancer.

Paclitaxel induces apoptosis through the TAK1-JNK activation pathway.

Paclitaxel (PTX) has previously been used to treat tumours of various tissue origins, such as lung, breast, ovarian, prostate cancers and leukemia. PTX-induced apoptosis is associated with p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), nuclear factor-kappa B (NF-κB) and c-Jun N-terminal kinase or stress-activated protein kinase (JNK/ SAPK) pathways. Transforming growth factor-beta-activated kinase 1 (TAK1) and TAK1-binding protein 1 (TAB1) play an important role in cell apoptosis through the p38, ERK, NF-κB and JNK signal transduction pathways. To investigate the role of TAK1 in PTX-induced cell apoptosis, we treated HEK293 and 8305C cells with 0-20 µM PTX for 6, 12 or 24 h. To investigate whether TAK1 can cooperate with PTX for cancer treatment, we transfected cells with TAK1, TAB1 or control plasmid and treated them with PTX (3-10 µM) for 9-24 h. Apoptosis rates were analysed by flow cytometry (Annexin V/PI). Endogenous TAK1 and TAB1, caspase-7 cleavage, poly ADP-ribose polymerase (PARP) cleavage, Bcl-xL level, phospho-p44/42, phospho-JNK and phospho-p38 were detected by western blot. We show that in HEK293 and 8305C cells, PTX enhanced the endogenous TAK1/TAB1 level and induced cell apoptosis in a dose- and time-dependent manner. Upon TAK1 overexpression in HEK293 cells treated with PTX, apoptosis rate, JNK phosphorylation and PARP cleavage increased contrary to heat-shocked or untreated cells. CRISPR editing of the tak1 gene upon PTX treatment resulted in lower phospho-JNK and PARP cleavage levels than in cells transfected with the control or the TAK1- or TAB1 + TAK1-containing plasmids. TAK1-K63A could not induce JNK phosphorylation or PARP cleavage. We conclude that PTX induces HEK293 and 8305C cell apoptosis through the TAK1-JNK activation pathway, potentially highlighting TAK1's role in chemosensitivity.

Antibodies against Schistosoma japonicum lactate dehydrogenase B enhance enzyme active.

Lactate dehydrogenase (LDH) is a key enzyme in glycolysis process. It catalyzes the interconversion between pyruvic acid and lactic acid. Schistosoma japonicum adult worms largely rely on glycolysis for energy production when they parasitize in human. S. japonicum may be killed if energy production is suppressed. So, we wonder whether antibody against S. japonicum LDH is a harmful factor for S. japonicum surviving. In this study, we cloned and characterized S. japonicum lactate dehydrogenase B (SjLDHB) to evaluate its role in parasite survival. We found SjLDHB was highly similar to S. japonicum lactate dehydrogenase A (SjLDHA) which is another LDH subtype in S. japonicum in amino acid sequence. The optimal temperature of SjLDHB catalytic activity was 37 °C, the optimal pH values for pyruvate reduction and lactate oxidation were 7.0 and 6.0 and Km values of pyruvate and lactate were 0.2752 and 0.2339 mM respectively. Then, we identified SjLDHB expression in male and female S. japonicum. Finally, we evaluated the influence of antibodies on SjLDHB enzymatic activity. Interestingly, we found anti-SjLDHA antibody suppressed SjLDHB enzymatic activity, while anti-SjLDHB antibody and mixed antibody enhanced SjLDHB enzymatic activity in vitro. Although further investigation is needed, we suggest that anti-SjLDHB antibody may be not a negative factor, but a valuable compensation for S. japonicum adult worm surviving and pathogenicity.

[Identification of a new 3.8kb deletional α thalassemia and detection of the deletion fragment].

OBJECTIVE: To report the identification of a novel 3.8-kb deletion that caused α thalassemia and establish the method for detecting the deletion fragment. METHODS: Peripheral blood samples were collected from the proband and his mother for analysis of the hematological parameters and routine test for thalassemia genes. For the sample with an inconsistency between the genotyping results and phenotypic analysis results, a specific gap-PCR was employed to identify the rare or novel mutations. RESULTS: A novel 3814-bp deletion causing α thalassemia was found in the proband and his mother, who had genotypes of -α4.2/-α3.8 and αα/-α3.8, respectively. CONCLUSION: We identified a 3.8-kb deletion in the α-globin gene cluster that caused α thalassemia, and this finding enriches the α thalassemia gene mutation spectrum. Specific gap-PCR offers a convenient and efficient means for for detecting this deletion fragment.

Shaping synaptic learning by the duration of postsynaptic action potential in a new STDP model.

Single spikes and their timing matter in changing synaptic efficacy, which is known as spike-timing-dependent plasticity (STDP). Most previous studies treated spikes as all-or-none events, and considered their duration and magnitude as negligible. Here we explore the effects of action potential (AP) duration on synaptic plasticity in a simplified model neuron using computer simulations. We propose a novel STDP model that depresses synapses using an AP duration dependent LTD window and induces potentiation of synaptic strength when presynaptic spikes arrive before and during a postsynaptic AP (dSTDP). We demonstrate that AP duration is another key factor for insensitizing the postsynaptic neural firing and for controlling the shape of synaptic weight distribution. Extended AP durations produce a wide unimodal weight distribution that resembles the ones reported experimentally and make the postsynaptic neuron tranquil when disturbed by poisson noise spike trains, while equivalently sensitive to the synchronized. Our results suggest that the impact of AP duration, modeled here as an AP-dependent STDP window, on synaptic plasticity can be dramatic and should motivate future STDP studies.