Recent advances in the natural product analogues for the treatment of neurodegenerative diseases.

Neurodegenerative diseases (NDs) represent a hallmark of numerous incapacitating and untreatable conditions, the incidence of which is escalating swiftly, exemplified by Alzheimer's disease and Parkinson's disease. There is an urgent necessity to create pharmaceuticals that exhibit high efficacy and minimal toxicity in order to address these debilitating diseases. The structural complexity and diversity of natural products confer upon them a broad spectrum of biological activities, thereby significantly contributing to the history of drug discovery. Nevertheless, natural products present challenges in drug discovery, including time-consuming separation processes, low content, low bioavailability, and other related issues. To address these challenges, numerous analogs of natural products have been synthesized. This methodology enables the rapid synthesis of analogs of natural products with the potential to serve as lead compounds for drug development, thereby paving the way for the discovery of novel pharmaceuticals. This paper provides a summary of 127 synthetic analogues featuring various natural product structures, including flavonoids, alkaloids, coumarins, phenylpropanoids, terpenoids, polyphenols, and amides. The compounds are categorized based on their efficacy in treating various diseases. Furthermore, this article delves into the structure-activity relationship (SAR) of certain analogues, offering a thorough point of reference for the systematic development of pharmaceuticals aimed at addressing neurodegenerative conditions.

Identification and characteristic analysis of an extracellular signal-regulated kinase from Ostrinia furnacalis Guenée.

The extracellular signal-regulated kinase (ERK) pathway, a critical genetic determinant, controls diverse physiological functions, including innate immunity, development, and stress response. In the current study, a full-length cDNA (1592bp) encoding the ERK gene (OfERK) was cloned from Ostrinia furnacalis Guenée (GenBank accession number: MF797866). The open reading frame of the OfERK gene encoded 364 amino acids and shared 96.43%-98.08% amino acid identities with other insect mitogen-activated protein kinases. For spatiotemporal analysis of the expression pattern, OfERK exhibited a significant peak expression on the 3rd day of the pupa stage and showed the highest expression in hemocytes specifically. Indirect immunofluorescence assays and immuno-electron microscopy revealed a wide distribution of the OfERK protein in hemocytes and epidermis. Moreover, the results demonstrated that the Bt Cry1Ab-activated toxin significantly induces the expression of OfERK. Other genes related to immune response, development, and stress response exhibited dynamic changes in expression after Cry1Ab oral treatment. The expression of OfERK was downregulated through RNA interference, and the correlation of its expression with other related genes was verified using quantitative real-time polymerase chain reaction. Our study provides valuable insights into the regulatory mechanism of ERK in insects for future studies.

Optical fiber vibration signal recognition based on an efficient multidimensional feature extraction network.

In the field of optical fiber vibration signal recognition, one-dimensional signals have few features. People often used the shallow layer of a one-dimensional convolutional neural network (1D-CNN), which results in fewer features being learned by the network, leading to a poor recognition rate. There are also many complex algorithms and data processing methods, which make the whole signal recognition process more complicated. Therefore, an optical vibration signal recognition method based on an efficient multidimensional feature extraction network was proposed. Based on ResNet-50, efficient channel attention (ECA) was used to improve image features extraction ability, and a long short-term memory (LSTM) network was used to enhance the extraction of temporal features. Three different vibration signals were collected using a phase-sensitive optical time-domain reflectometry (Φ-OTDR) optical fiber sensing system. Vibration signals were converted into 128×128 grayscale images, which have more effective vibration information. The experimental results show that the three types of signals can be recognized and classified effectively by the network, and the average recognition rate is 98.67%.

Silicon-Nanomembrane-Based Broadband Synaptic Phototransistors for Neuromorphic Vision.

Neuromorphic vision has been attracting much attention due to its advantages over conventional machine vision (e.g., lower data redundancy and lower power consumption). Here we develop synaptic phototransistors based on the silicon nanomembrane (Si NM), which are coupled with lead sulfide quantum dots (PbS QDs) and poly(3-hexylthiophene) (P3HT) to form a heterostructure with distinct photogating. Synaptic phototransistors with optical stimulation have outstanding synaptic functionalities ranging from ultraviolet (UV) to near-infrared (NIR). The broadband synaptic functionalities enable an array of synaptic phototransistors to achieve the perception of brightness and color. In addition, an array of synaptic phototransistors is capable of simultaneous sensing, processing, and memory, which well mimics human vision.

Lead-Chelating Intermediate for Air-Processed Phase-Pure FAPbI3 Perovskite Solar Cells.

Formamidinium-lead triiodide (FAPbI3) perovskite holds promise as a prime candidate in the realm of perovskite photovoltaics. However, the photo-active α-FAPbI3 phase, existing as a metastable state, is observable solely at elevated temperatures and is susceptible to degradation into the δ-phase in ambient air. Therefore, the attainment of phase-stable α-FAPbI3 in ambient conditions has become a crucial objective in perovskite research. Here, we proposed an efficient conversion process of PbI2 into the α-FAPbI3 perovskites in ambient air. This conversion was facilitated by the introduction of chelating molecules, which interacted with PbI2 to form an intermediate phase. Due to the reduced formation barrier resulting from the altered reaction pathway, this stable intermediate phase transitioned directly into α-FAPbI3 upon the deposition of the organic cation solution, effectively bypassing the formation of δ-FAPbI3. Consequently, the ambient-fabricated FAPbI3 perovskite solar cells (PSCs) exhibited an outstanding power conversion efficiency of 25.08 %, along with a high open-circuit voltage of 1.19 V. Furthermore, the unencapsulated devices demonstrated remarkable environmental stability. Notably, this innovative approach promises broad applicability across various chelating molecules, opening new avenues for further progress in the ambient air fabrication of FAPbI3 PSCs.

Genetic association and causal inference between lung function and venous thromboembolism.

BACKGROUND: Previous studies have indicated that lower lung function is related to a higher risk of venous thromboembolism (VTE). However, causal inferences may be affected by confounders, coheritability or reverse causality. We aimed to explore the causal association between lung function and VTE. METHODS: Summary data from public genome-wide association studies (GWAS) for lung function and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly related to exposure were filtered as proxy instruments. We adopted linkage disequilibrium score regression (LDSC) and two-sample Mendelian randomization (MR) analyses to infer the genetic backgrounds and causal associations between different lung functions and VTE events. RESULTS: LDSC showed a genetic correlation between forced expiratory volume in one second (FEV1) and deep vein thrombosis (DVT) (rg = - 0.189, P = 0.005). In univariate MR (UVMR), there was suggestive evidence for causal associations of genetically predicted force vital capacity (FVC) with DVT (odds ratio (OR) 0.774; 95% confidence interval (CI) 0.641-0.934) via forwards analysis and genetically predicted pulmonary embolism (PE) with FVC (OR 0.989; 95% CI 0.979-0.999) via reverse analysis. Multivariate MR (MVMR) analyses of lung function-specific SNPs suggested no significant direct effects of lung function on VTE, and vice versa. Of note is the borderline causal effect of PE on FEV1 (OR 0.921; 95% CI 0.848-1.000). CONCLUSIONS: Our findings identified a coheritability of FEV1 (significant) and FVC (suggestive) with DVT. There was no convincing causal relationship between lung function and the risk of VTE events. The borderline causal effect of PE on FEV1 and the significant genetic correlation of FEV1 with DVT may have clinical implications for improving the quality of existing prevention and intervention strategies.

The Effects of Perioperative Probiotics on Postoperative Gastrointestinal Function in Patients with Brain Tumors: A Randomized, Placebo-Controlled Study.

The incidence of postoperative gastrointestinal dysfunction among neurosurgical patients is as high as 80%. Probiotics help to maintain gastrointestinal barrier defense, provide competitive adherence to mucus and epithelial cells, and regulate gastrointestinal motility. Therefore, the purpose of this study was to investigate whether probiotics enhance gastrointestinal health after craniotomy in patients with brain tumors. This study was a 15-day, prospective, randomized, double-blind, placebo-controlled trial for patients being treated with elective craniotomy for brain tumors. Participants were randomly divided into the probiotics group (4 g probiotics, twice daily) and placebo group. The primary outcome was the time of first stool after surgery. The secondary outcomes included assessments of the gastrointestinal function, changes in gastrointestinal permeability and clinical outcomes. We enrolled a total of 200 participants (probiotics: 100; placebo: 100) and followed the principles of intention-to-treat analysis. The time of first stool and flatus were significantly shorter in the probiotics group compared to the placebo group (P < 0.001, respectively). No significant trends were observed for any other of the secondary outcome variables. Our findings suggest that probiotics can improve the gastrointestinal mobility of patients received craniotomy, and this improvement cannot be explained by changes in gastrointestinal permeability.

Molecular beam epitaxy growth and scanning tunneling microscopy study of 2D layered materials on epitaxial graphene/silicon carbide.

Since the advent of atomically flat graphene, two-dimensional (2D) layered materials have gained extensive interest due to their unique properties. The 2D layered materials prepared on epitaxial graphene/silicon carbide (EG/SiC) surface by molecular beam epitaxy (MBE) have high quality, which can be directly applied without further transfer to other substrates. Scanning tunneling microscopy and spectroscopy (STM/STS) with high spatial resolution and high-energy resolution are often used to study the morphologies and electronic structures of 2D layered materials. In this review, recent progress in the preparation of various 2D layered materials that are either monoelemental or transition metal dichalcogenides on EG/SiC surface by MBE and their STM/STS investigations are introduced.

Mallory-Weiss syndrome in four hemodialysis patients: a case study.

BACKGROUND: Hemodialysis patients are prone to gastrointestinal bleeding, and Mallory-Weiss syndrome (MWS) is one of the causes. Mallory-Weiss syndrome is often induced by severe vomiting, manifests as upper gastrointestinal bleeding, and is self-limited with a good prognosis. However, mild vomiting in hemodialysis patients can lead to the occurrence of MWS, and the mild early symptoms are easy to misdiagnose, leading to the aggravation of the disease. CASE PRESENTATION: In this paper, we report four hemodialysis patients with MWS. All patients displayed symptoms of upper gastrointestinal bleeding. The diagnosis of MWS was confirmed by gastroscopy. One patient had a history of severe vomiting; however, the other three reported histories of mild vomiting. Three patients received the conservative hemostasis treatment, and the gastrointestinal bleeding stopped. One patient underwent the gastroscopic and interventional hemostasis treatments. The conditions of three of the patients improved. Unfortunately, one of the patients died due to the cardia insufficiency. CONCLUSIONS: We think that the mild symptoms of MWS are easily covered up by other symptoms. This may lead to delays in diagnosis and treatment. For patients with severe symptoms, gastroscopic hemostasis is still the first choice, and interventional hemostasis can also be considered. For patients with mild symptoms, drug hemostasis is the first consideration.

Real-Time Ocean Current Compensation for AUV Trajectory Tracking Control Using a Meta-Learning and Self-Adaptation Hybrid Approach.

Autonomous underwater vehicles (AUVs) may deviate from their predetermined trajectory in underwater currents due to the complex effects of hydrodynamics on their maneuverability. Model-based control methods are commonly employed to address this problem, but they suffer from issues related to the time-variability of parameters and the inaccuracy of mathematical models. To improve these, a meta-learning and self-adaptation hybrid approach is proposed in this paper to enable an underwater robot to adapt to ocean currents. Instead of using a traditional complex mathematical model, a deep neural network (DNN) serving as the basis function is trained to learn a high-order hydrodynamic model offline; then, a set of linear coefficients is adjusted dynamically by an adaptive law online. By conjoining these two strategies for real-time thrust compensation, the proposed method leverages the potent representational capacity of DNN along with the rapid response of adaptive control. This combination achieves a significant enhancement in tracking performance compared to alternative controllers, as observed in simulations. These findings substantiate that the AUV can adeptly adapt to new speeds of ocean currents.

Dredging the Charge-Carrier Transfer Pathway for Efficient Low-Dimensional Ruddlesden-Popper Perovskite Solar Cells.

Low-dimensional Ruddlesden-Popper (LDRP) perovskites still suffer from inferior carrier transport properties. Here, we demonstrate that efficient exciton dissociation and charge transfer can be achieved in LDRP perovskite by introducing γ-aminobutyric acid (GABA) as a spacer. The hydrogen bonding links adjacent spacing sheets in (GABA)2 MA3 Pb4 I13 (MA=CH3 NH3 + ), leading to the charges localized in the van der Waals gap, thereby constructing "charged-bridge" for charge transfer through the spacing region. Additionally, the polarized GABA weakens dielectric confinement, decreasing the (GABA)2 MA3 Pb4 I13 exciton binding energy as low as ≈73 meV. Benefiting from these merits, the resultant GABA-based solar cell yields a champion power conversion efficiency (PCE) of 18.73 % with enhanced carrier transport properties. Furthermore, the unencapsulated device maintains 92.8 % of its initial PCE under continuous illumination after 1000 h and only lost 3 % of its initial PCE under 65 °C for 500 h.

Cardiac Regeneration and Stem Cells.

After decades of believing the heart loses the ability to regenerate soon after birth, numerous studies are now reporting that the adult heart may indeed be capable of regeneration, although the magnitude of new cardiac myocyte formation varies greatly. While this debate has energized the field of cardiac regeneration and led to a dramatic increase in our understanding of cardiac growth and repair, it has left much confusion in the field as to the prospects of regenerating the heart. Studies applying modern techniques of genetic lineage tracing and carbon-14 dating have begun to establish limits on the amount of endogenous regeneration after cardiac injury, but the underlying cellular mechanisms of this regeneration remained unclear. These same studies have also revealed an astonishing capacity for cardiac repair early in life that is largely lost with adult differentiation and maturation. Regardless, this renewed focus on cardiac regeneration as a therapeutic goal holds great promise as a novel strategy to address the leading cause of death in the developed world.

Phase-Stable Wide-Bandgap Perovskites for Four-Terminal Perovskite/Silicon Tandem Solar Cells with Over 30% Efficiency.

Wide-bandgap perovskite solar cells (PSCs) with an optimal bandgap between 1.7 and 1.8 eV are critical to realize highly efficient and cost-competitive silicon tandem solar cells (TSCs). However, such wide-bandgap PSCs easily suffer from phase segregation, leading to performance degradation under operation. Here, it is evident that ammonium diethyldithiocarbamate (ADDC) can reduce the detrimental I2 back to I- in precursor solution, thereby reducing the density of deep level traps in perovskite films. The resultant perovskite film exhibits great phase stability under continuous illumination and 30-60% relative humidity conditions. Due to the suppression of defect proliferation and ion migration, the PSCs deliver great operation stability which retain over 90% of the initial power conversion efficiency (PCE) after 500 h maximum power point tracking. Finally, a highly efficient semitransparent PSC with a tailored bandgap of 1.77 eV, achieving a PCE approaching 18.6% with a groundbreaking open-circuit voltage (VOC ) of 1.24 V enabled by ADDC additive in perovskite films is demonstrated. Integrated with a bottom silicon solar cell, a four-terminal (4T) TSC with a PCE of 30.24% is achieved, which is one of the highest efficiencies in 4T perovskite/silicon TSCs.

Chemerin regulates formation and function of brown adipose tissue: Ablation results in increased insulin resistance with high fat challenge and aging.

Apart from its role in inflammation and immunity, chemerin is also involved in white adipocyte biology. To study the role of chemerin in adipocyte metabolism, we examined the function of chemerin in brown adipose tissue. Brown and white adipocyte precursors were differentiated into adipocytes in the presence of Chemerin siRNA. Chemerin-deficient (Chem-/- ) mice were compared to wild-type mice when fed a high-fat diet. Chemerin is expressed during brown adipocyte differentiation and knock down of chemerin mRNA results in decreased brown adipocyte differentiation with reduced fatty acid uptake in brown adipocytes. Chem-/- mice are leaner than wild-type mice but gain more weight when challenged with high-fat diet feeding, resulting in a larger increase in fat deposition. Chem-/- mice develop insulin resistance when on a high-fat diet or due to age. Brown adipose depots in Chem-/- mice weigh more than in wild-type mice, but with decreased mitochondrial content and function. Compared to wild-type mice, male Chem-/- mice have decreased oxygen consumption, CO2 production, energy expenditure, and a lower respiratory exchange ratio. Additionally, body temperature of Chem-/- mice is lower than that of wild-type mice. These results revealed that chemerin is expressed during brown adipocyte differentiation and has a pivotal role in energy metabolism through brown adipose tissue thermogenesis.

Vascular endothelial growth factor and the risk of venous thromboembolism: a genetic correlation and two-sample Mendelian randomization study.

BACKGROUND: The relationship between vascular endothelial growth factor (VEGF) and the risk of venous thromboembolism (VTE) has always been one of the concerns in the medical field. However, the causal inferences from published observational studies on this issue may be affected by confounders or reverse causality. We performed a two-sample bidirectional Mendelian randomization (MR) to infer the associations between VEGF and VTE. METHODS: Summary statistics from genome-wide association studies (GWAS) for VEGF and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly associated with exposure were selected as instrumental variables. Linkage disequilibrium score regression (LDSC) and five robust MR analytical approaches were conducted to estimate the genetic correlations and causal inference. The MR-Egger intercept, Cochran's Q, and MR pleiotropy residual sum and outlier (MR-PRESSO) were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on outcomes. Notably, replication analyses were performed using different subgroups of VTE. RESULTS: LDSC failed to identify genetic correlations between VEGF and VTE. Based on 9 SNPs, the circulating VEGF level was positively related to the risk of VTE using inverse variance weighting (IVW) method (odds ratio (OR) = 1.064, 95% confidence interval (CI), 1.009-1.122). Reverse MR analyses showed that genetic liability for VTE was not associated with increased VEGF level (ß = -0.021, 95% CI, -0.087-0.045). Pleiotropy-robust methods indicated no bias in any estimates. CONCLUSIONS: Our findings failed to detect coheritability between VEGF and VTE. The suggestive positive effect of the higher VEGF level on the VTE risk may have clinical implications, suggesting that VEGF as a possible predictor and therapeutic target for VTE prevention need to be further warranted.

Causal associations between COVID-19 and atrial fibrillation: A bidirectional Mendelian randomization study.

BACKGROUND AND AIMS: Observational studies showed that coronavirus disease (2019) (COVID-19) attacks universally and its most menacing progression uniquely endangers the elderly with cardiovascular disease (CVD). The causal association between COVID-19 infection or its severity and susceptibility of atrial fibrillation (AF) remains unknown. METHODS AND RESULTS: The bidirectional causal relationship between COVID-19 (including COVID-19, hospitalized COVID-19 compared with not hospitalized COVID-19, hospitalized COVID-19 compared with the general population, and severe COVID-19) and AF are determined by using two-sample Mendelian randomization (MR) analysis. Genetically predicted severe COVID-19 was not significantly associated with the risk of AF [odds ratio (OR), 1.037; 95% confidence interval (CI), 1.005-1.071; P = 0.023, q = 0.115]. In addition, genetically predicted AF was also not causally associated with severe COVID-19 (OR, 0.993; 95% CI, 0.888-1.111; P = 0.905, q = 0.905). There was no evidence to support the association between genetically determined COVID-19 and the risk of AF (OR, 1.111; 95% CI, 0.971-1.272; P = 0.127, q = 0.318), and vice versa (OR, 1.016; 95% CI, 0.976-1.058; P = 0.430, q = 0.851). Besides, no significant association was observed for hospitalized COVID-19 with AF. MR-Egger analysis indicated no evidence of directional pleiotropy. CONCLUSION: Overall, this MR study provides no clear evidence that COVID-19 is causally associated with the risk of AF.

From Structural Design to Functional Construction: Amine Molecules in High-Performance Formamidinium-Based Perovskite Solar Cells.

Formamidinium (FA) based perovskites are considered as one of the most promising light-absorbing perovskite materials owing to their narrower band gap and better thermal stability compared to conventional methylammonium-based perovskites. Constant improvement by using various additives stimulates the potential application of these perovskites. Amine molecules with different structures have been widely used as typical additives in FA-based perovskite solar cells, and decent performances have been achieved. Thus, a systematic review focusing on structural regulation and functional construction of amines in FA-based perovskites is of significance. Herein, we analyze the construction mechanism of different structural amines on the functional perovskite crystals. The influence of amine molecules on specific perovskite properties including defect conditions, charge transfer, and moisture resistance are evaluated. Finally, we summarize the design rules of amine molecules for the application in high-performance FA-based perovskites and propose directions for the future development of additive molecules.

Vacuum-Assisted Thermal Annealing of CsPbI3 for Highly Stable and Efficient Inorganic Perovskite Solar Cells.

Inorganic cesium lead iodide perovskite CsPbI3 is attracting great attention as a light absorber for single or multi-junction photovoltaics due to its outstanding thermal stability and proper band gap. However, the device performance of CsPbI3 -based perovskite solar cells (PSCs) is limited by the unsatisfactory crystal quality and thus severe non-radiative recombination. Here, vacuum-assisted thermal annealing (VATA) is demonstrated as an effective approach for controlling the morphology and crystallinity of the CsPbI3 perovskite films formed from the precursors of PbI2 , CsI, and dimethylammonium iodide (DMAI). By this method, a large-area and high-quality CsPbI3 film is obtained, exhibiting a much reduced trap-state density with prolonged charge lifetime. Consequently, the solar cell efficiency is raised from 17.26 to 20.06 %, along with enhanced stability. The VATA would be an effective approach for fabricating high-performance thin-film CsPbI3 perovskite optoelectronics.

Design of Low Bandgap CsPb1- x Snx I2 Br Perovskite Solar Cells with Excellent Phase Stability.

Novel all-inorganic Sn-Pb alloyed perovskites are developed aiming for low toxicity, low bandgap, and long-term stability. Among them, CsPb1- x Snx I2 Br is predicted as an ideal perovskite with favorable band gap, but previously is demonstrated unable to convert to perovskite phase by thermal annealing. In this report, a series of CsPb1- x Snx I2 Br perovskites with tunable bandgaps from 1.92 to 1.38 eV are successfully prepared for the first time via low annealing temperature (60 °C). Compared to the pure CsPbI2 Br, these Sn-Pb alloyed perovskites show superior stability. Furthermore, a novel α-phase-stabilization mechanism of the inorganic Sn-Pb alloyed perovskite by reconfiguring the perovskite crystallization process with chloride doping is provided. Simultaneously, a dense protection layer is formed by the coordination reaction between the surface lead dangling bonds and sulfate ion to retard the permeation of external oxygen and moisture, leading to less oxidation of Sn2+ in perovskite film. As a result, the fabricated all-inorganic Sn-Pb perovskite solar cells (PSCs) show a champion power conversion efficiency of 10.39% with improved phase stability and long-term ambient stability against light, heat, and humidity. This work provides a viable strategy in fabricating high-performance narrow-bandgap all-inorganic PSCs.

Low-temperature processed tantalum/niobium co-doped TiO2electron transport layer for high-performance planar perovskite solar cells.

A low-temperature preparation process is significantly important for scalable and flexible devices. However, the serious interface defects between the normally used titanium dioxide (TiO2) electron transport layer (ETL) obtained via a low-temperature method and perovskite suppress the further improvement of perovskite solar cells (PSCs). Here, we develop a facile low-temperature chemical bath method to prepare a TiO2ETL with tantalum (Ta) and niobium (Nb) co-doping. Systematic investigations indicate that Ta/Nb co-doping could increase the conduction band level of TiO2and could decrease the trap-state density, boosting electron injection efficiency and reducing the charge recombination between the perovskite/ETL interface. A superior power conversion efficiency of 19.44% can be achieved by a planar PSC with a Ta/Nb co-doped TiO2ETL, which is much higher than that of pristine TiO2(17.60%). Our achievements in this work provide new insights on low-temperature fabrication of low-cost and highly efficient PSCs.