Ultrasensitive 3D Stacked Silicon Nanosheet Field-Effect Transistor Biosensor with Overcoming Debye Shielding Effect for Detection of DNA.

Silicon nanowire field effect (SiNW-FET) biosensors have been successfully used in the detection of nucleic acids, proteins and other molecules owing to their advantages of ultra-high sensitivity, high specificity, and label-free and immediate response. However, the presence of the Debye shielding effect in semiconductor devices severely reduces their detection sensitivity. In this paper, a three-dimensional stacked silicon nanosheet FET (3D-SiNS-FET) biosensor was studied for the high-sensitivity detection of nucleic acids. Based on the mainstream Gate-All-Around (GAA) fenestration process, a three-dimensional stacked structure with an 8 nm cavity spacing was designed and prepared, allowing modification of probe molecules within the stacked cavities. Furthermore, the advantage of the three-dimensional space can realize the upper and lower complementary detection, which can overcome the Debye shielding effect and realize high-sensitivity Point of Care Testing (POCT) at high ionic strength. The experimental results show that the minimum detection limit for 12-base DNA (4 nM) at 1 × PBS is less than 10 zM, and at a high concentration of 1 µM DNA, the sensitivity of the 3D-SiNS-FET is approximately 10 times higher than that of the planar devices. This indicates that our device provides distinct advantages for detection, showing promise for future biosensor applications in clinical settings.

The development of a clinical nomogram to predict medication nonadherence in patients with knee osteoarthritis.

Knee osteoarthritis (KOA) is a common bone disease in older patients. Medication adherence is of great significance in the prognosis of this disease. Therefore, this study analyzed the high-risk factors that lead to medication nonadherence in patients with KOA and constructed a nomogram risk prediction model. The basic information and clinical characteristics of inpatients diagnosed with KOA at the Department of Orthopedics, The Affiliated Hospital of Chengde Medical University, were collected from January 2020 to January 2022. The Chinese version of the eight-item Morisky scale was used to evaluate medication adherence. The Kellgren-Lawrence (KL) classification was performed in combination with the imaging data of patients. Least absolute shrinkage and selection operator regression analysis and logistic multivariate regression analysis were used to analyze high-risk factors leading to medication nonadherence, and a prediction model of the nomogram was constructed. The model was internally verified using bootstrap self-sampling. The index of concordance (C-index), area under the operating characteristic curve (AUC), decision curve, correction curve, and clinical impact curve were used to evaluate the model. A total of 236 patients with KOA were included in this study, and the non-adherence rate to medication was 55.08%. Seven influencing factors were included in the nomogram prediction: age, underlying diseases, diabetes, age-adjusted Charlson comorbidity index (aCCI), payment method, painkillers, and use of traditional Chinese medicine. The C-index and AUC was 0.935. The threshold probability of the decision curve analysis was 0.02-0.98. The nomogram model can be effectively applied to predict the risk of medication adherence in patients with KOA, which is helpful for medical workers to identify and predict the risk of individualized medication adherence in patients with KOA at an early stage of treatment, and then carry out early intervention.

Regulation of capsule spine formation in castor.

Castor (Ricinus communis L.) is a dicotyledonous oilseed crop that can have either spineless or spiny capsules. Spines are protuberant structures that differ from thorns or prickles. The developmental regulatory mechanisms governing spine formation in castor or other plants have remained largely unknown. Herein, using map-based cloning in 2 independent F2 populations, F2-LYY5/DL01 and F2-LYY9/DL01, we identified the RcMYB106 (myb domain protein 106) transcription factor as a key regulator of capsule spine development in castor. Haplotype analyses demonstrated that either a 4,353-bp deletion in the promoter or a single nucleotide polymorphism leading to a premature stop codon in the RcMYB106 gene could cause the spineless capsule phenotype in castor. Results of our experiments indicated that RcMYB106 might target the downstream gene RcWIN1 (WAX INDUCER1), which encodes an ethylene response factor known to be involved in trichome formation in Arabidopsis (Arabidopsis thaliana) to control capsule spine development in castor. This hypothesis, however, remains to be further tested. Nevertheless, our study reveals a potential molecular regulatory mechanism underlying the spine capsule trait in a nonmodel plant species.

A Polarization-Switching, Charge-Trapping, Modulated Arithmetic Logic Unit for In-Memory Computing Based on Ferroelectric Fin Field-Effect Transistors.

Nonvolatile logic devices are crucial for the development of logic-in-memory (LiM) technology to build the next-generation non-von Neumann computing architecture. Ferroelectric field-effect transistors (Fe FET) are one of the most promising candidates for LiMs because of high compatibility with mainstream silicon-based complementary metal-oxide semiconductor processes, nonvolatile memory, and low power consumption. However, because of the unipolar characteristics of a Fe FET, a nonlinear XOR or XNOR logic gate function is difficult to realize with a single device. In addition, because single Fe polarization switch modulation is available in the devices, a reconfigurable logic gate usually needs multiple devices to construct and realize fewer logic functions. Here, we introduced polarization-switching (PS) and charge-trapping (CT) effects in a single Fe FET and fabricated a multi-field-effect transistor with bipolar-like characteristics based on advanced 10 nm node fin field-effect transistors (PS-CT FinFET) with 9 nm thick Hf0.5Zr0.5O2 films. The special hybrid effects of charge-trapping and polarization-switching enabled eight Boolean logic functions with a single PS-CT FinFET and 16 Boolean logic functions with two complementary PS-CT FinFETs were obtained with three operations. Furthermore, reconfigurable full 1 bit adder and subtractor functions were demonstrated by connecting only two n-type and two p-type PS-CT FinFET devices, indicating that the technology was promising for LiM applications.

Systematic characterization of the metabolites of defatted walnut powder extract in vivo and screening of the mechanisms against NAFLD by UPLC-Q-Exactive Orbitrap MS combined with network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Walnut kernel, a well-known TCM, is often used after being defatted in tradition. And defatted walnut powder extract (DWPE) has the actions of tonifying the liver and kidney, dissipating stagnation and removing blood stasis, which has the effect on non-alcoholic fatty liver disease (NAFLD). However, the effective components of DWPE in vivo were unclear and the multiple mechanisms of DWPE against NAFLD have not been explored. AIM OF THE STUDY: The studies were performed to screen the effective substances in vivo by identification of the metabolites of DWPE in rats and to seek the potential mechanisms of DWPE on NAFLD by construction of the network pharmacology based on metabolites and verification of the highly correlated pathway. MATERIALS AND METHODS: To explore the effective substances in vivo, the metabolites of DWPE were identified in SD rats' bio-samples through UPLC-Q-Exactive Orbitrap MS. To analyze the mechanisms of DWPE on NAFLD, a Metabolite-Target-Disease network was established and the potential mechanisms were predicted. Then, highly correlated pathway was verified in animal and cells studies. RESULTS: A total of 52 metabolites of DWPE were identified in vivo, which were derived from gallic acid, ellagic acid (EA) and glansreginin A (Gla A). The possible metabolic pathways were phase Ⅰ (hydroxylation, hydrolyzation, etc) and phase Ⅱ metabolic reactions (methylation, sulfation and glucuronidation). Furthermore, in the network pharmacology, 54 core targets were enriched into pathways in cancer, nitrogen metabolism and other 9 pathways, which were essential pathways of DWPE against NAFLD. And the mechanism of nitrogen metabolism was verified in both of animal and cells studies. The results showed that DWPE could decline the concentration of ammonia and increase the expressions of carbonic anhydrase 2 (CA2) and carbamoylphosphate synthetase (CPS1) in nitrogen metabolism. CONCLUSION: Taken together, the study revealed the absorption components and their metabolic pathways and demonstrated the mechanism of nitrogen metabolism of DWPE on anti-NAFLD.

Anti-NAFLD effect of defatted walnut powder extract in high fat diet-induced C57BL/6 mice by modulating the gut microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Walnut kernel has the actions of removing meteorism, dissipating stagnation and removing blood stasis and is used after being defatted in TCM. Defatted walnut powder extract (DWPE) has the abilities of anti-oxidation and lowering lipid levels in vivo. However, the effects and the potential mechanisms of DWPE on NAFLD have not been explored. AIM OF THE STUDY: The study were to investigate the anti-NAFLD effect of DWPE in high fat diet-induced C57BL/6 mice and demonstrate that whether DWPE developed the effect on anti-NAFLD by remodeling the compositions and abundances of gut microbiota. MATERIALS AND METHODS: The inhibitory effect of DWPE on the development of NAFLD was conducted on C57BL/6 mice with a high fat diet and the regulation effect of DWPE on gut microbiota was verified on pseudo-sterile mice with treatment of broad spectrum antibiotics. RESULTS: The results showed that the oral administration of DWPE remarkably alleviated hepatic lipid accumulation by decreasing the levels of TG, TC, LDL, MDA and increasing HDL. Meanwhile, the expressions of NF-κB and MAPKs family proteins were reduced by DWPE compared with HFD group. Otherwise, the efficacy of anti-NAFLD of DWPE was significantly decreased after treatment of antibiotics, which indicated the key role of gut microbiota in the therapeutic process. Furthermore, sequencing of 16S rRNA gene revealed that DWPE could revert the decreased relative abundance of gut microbiota caused by the long term of a high fat diet. And the disordered microflora was remodeled by DWPE including the reduction of Erysipelotrichia, Firmicutes and Actinobacteria as well as the increment of Bacteroidetes, Clostridiales, Bacteroidales S24-7, Prevotellaceae and Bacteroides. CONCLUSION: Taken together, DWPE had a preventing effect on NAFLD, which might be associated with the regulation of gut microbiota.

[Effect of Bushen Gujin Recipe on serum and synovia interleukin-1 and tumor necrosis factor-alpha of knee osteoarthritis model rabbits].

OBJECTIVE: To explore the effect of Bushen Gujin Recipe (BGR) on serum and synovial expression of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α) in knee osteoarthritis (KOA) model rabbits. METHODS: Totally 36 8-month-old healthy male New Zealand white rabbits were randomly divided into 4 groups, i.e., the normal control group, the model group, the Western medicine group (Meloxicam, at the daily dose of 6 mg/kg), and the TCM group (BGR, at the daily dose of 53 g/kg), 9 in each group. Modeling was performed in all rabbits except those in the normal control group by using Hulth A method. All medication was performed for 8 consecutive weeks. Contents of IL-1 and TNF-α were detected using ELISA from serum, partial synovial tissue of the front knee joint, cartilage and subchondral bone of the medial femoral condyle. RESULTS: The joint space became narrowed in the Western medicine group, ranging between the model group and the TCM group. The articular surface was rough with obvious osteophytes. The joint space was slightly narrower in the TCM group; the articular surface was slightly rough with mild osteophytes. Compared with the normal control group, contents of IL-1 and TNF-α in serum and synovial increased in the model group (P < 0.01). Compared with the model group, contents of IL-1 and TNF-α in serum and the synovial fluid decreased in the two treatment groups (P < 0.01). There was no statistical difference in contents of IL-1 and TNF-α between the Western medicine group and the TCM group. CONCLUSION: BGR promoted the synthesis of cartilage matrix and carti- lage repair through inhibiting the secretion of IL-1 and TNF-α, and prolonging cartilage degeneration.