The emergence of machine learning force fields in drug design.

In the field of molecular simulation for drug design, traditional molecular mechanic force fields and quantum chemical theories have been instrumental but limited in terms of scalability and computational efficiency. To overcome these limitations, machine learning force fields (MLFFs) have emerged as a powerful tool capable of balancing accuracy with efficiency. MLFFs rely on the relationship between molecular structures and potential energy, bypassing the need for a preconceived notion of interaction representations. Their accuracy depends on the machine learning models used, and the quality and volume of training data sets. With recent advances in equivariant neural networks and high-quality datasets, MLFFs have significantly improved their performance. This review explores MLFFs, emphasizing their potential in drug design. It elucidates MLFF principles, provides development and validation guidelines, and highlights successful MLFF implementations. It also addresses potential challenges in developing and applying MLFFs. The review concludes by illuminating the path ahead for MLFFs, outlining the challenges to be overcome and the opportunities to be harnessed. This inspires researchers to embrace MLFFs in their investigations as a new tool to perform molecular simulations in drug design.

Rutin alleviated lipopolysaccharide-induced damage in goat rumen epithelial cells.

OBJECTIVE: Rutin, also called vitamin P, is a flavonoids from plants. Previous studies have indicated that rutin can alleviate the injury of tissues and cells by inhibiting oxidative stress and ameliorating inflammation. There is no report on the protective effects of rutin on goat rumen epithelial cells (GRECs) at present. Hence, we investigated whether rutin can alleviate lipopolysaccharide (LPS)-induced damage in GRECs. METHODS: GRECs were cultured in basal medium or basal medium containing 1 µg/mL LPS, or 1 µg/mL LPS and 20 µg/mL rutin. Six replicates were performed for each group. After 3-h culture, the GRECs were harvested to detect the relevant parameters. RESULTS: Rutin significantly enhanced the cell activity (p<0.05) and transepithelial electrical resistance (TEER) (p<0.01) and significantly reduced the apoptosis rate (p<0.05) of LPSinduced GRECs. Rutin significantly increased superoxide dismutase, glutathione peroxidase, and catalase activity (p<0.01) and significantly decreased lactate dehydrogenase activity and reactive oxygen species and malondialdehyde (MDA) levels in LPS-induced GRECs (p<0.01). The mRNA and protein levels of interleukin 6 (IL-6), IL-1ß, and C-X-C motif chemokine ligand 8 (CXCL8) and the mRNA level of tumor necrosis factor-α (TNF-α) and chemokine C-C motif ligand 5 (CCL5) were significantly increased in LPS-induced GRECs (p<0.05 or p<0.01), while rutin supplementation significantly decreased the mRNA and protein levels of IL-6, TNF-α, and CXCL8 in LPS-induced GRECs (p<0.05 or p<0.01). The mRNA level of toll-like receptor 2 (TLR2), and the mRNA and protein levels of TLR4 and nuclear factor κB (NF-κB) was significantly improved in LPS-induced GRECs (p<0.05 or p<0.01), whereas rutin supplementation could significantly reduce the mRNA and protein levels of TLR4 (p<0.05 or p<0.01). In addition, rutin had a tendency of decreasing the protein levels of CXCL6, NF-κB, and inhibitor of nuclear factor kappa-B alpha (0.05< p<0.10). Rutin could significantly decreased interferon regulatory factor 3 mRNA expression in LPS-induced GRECs (p<0.05), whereas interferon induced protein with tetratricopeptide repeats 3 (IFIT3) and toll-interacting protein (TOLLIP) mRNA expression was not significantly different between the groups. LPS reduced the tight junction protein zonula occludin 1 (ZO-1) level in GRECs whereas rutin enhanced it. Rutin significantly improved tight junction protein Claudin-1 mRNA expression in LPS-induced GRECs (p<0.01), but could not affect tight junction protein Occludin mRNA expression. CONCLUSION: Rutin alleviated LPS-induced barrier damage in GRECs by improving oxidation resistance and anti-inflammatory activity, which may be related to TLR/NF-κB signaling pathway inhibition.

Enhanced CO2 Reactive Capture and Conversion Using Aminothiolate Ligand-Metal Interface.

Metallic catalyst modification by organic ligands is an emerging catalyst design in enhancing the activity and selectivity of electrocatalytic carbon dioxide (CO2) reactive capture and reduction to value-added fuels. However, a lack of fundamental science on how these ligand-metal interfaces interact with CO2 and key intermediates under working conditions has resulted in a trial-and-error approach for experimental designs. With the aid of density functional theory calculations, we provided a comprehensive mechanism study of CO2 reduction to multicarbon products over aminothiolate-coated copper (Cu) catalysts. Our results indicate that the CO2 reduction performance was closely related to the alkyl chain length, ligand coverage, ligand configuration, and Cu facet. The aminothiolate ligand-Cu interface significantly promoted initial CO2 activation and lowered the activation barrier of carbon-carbon coupling through the organic (nitrogen (N)) and inorganic (Cu) interfacial active sites. Experimentally, the selectivity and partial current density of the multicarbon products over aminothiolate-coated Cu increased by 1.5-fold and 2-fold, respectively, as compared to the pristine Cu at -1.16 VRHE, consistent with our theoretical findings. This work highlights the promising strategy of designing the ligand-metal interface for CO2 reactive capture and conversion to multicarbon products.

Effects of rutin supplementation on growth performance, slaughter performance, serum parameters, and meat quality of Nubian goats.

Previous studies found that rutin can improve production performance of sheep and dairy cows. However, it is not clear whether rutin has similar effects in goats. Hence, the aim of this experiment was to study the effects of rutin supplementation on growth performance, slaughter performance, serum parameters, and meat quality of Nubian goats. A total of 36 healthy Nubian ewes were randomly divided into three groups. Goats were fed the basal diet supplemented with 0 (R0), 25 (R25), and 50 (R50) mg rutin per kg of diet. The growth performance and slaughter performance of goats had no significant difference among three groups. The meat pH45min and moisture were significantly higher in the R25 group than the R50 group (p < 0.05), but the color value b* and contents of C14:0, C16:0, C18:0, C18:1n9c, C20:1, saturated fatty acid (SFA), and monounsaturated fatty acid (MSFA) in meat had an opposite outcome. The dressing percentage had an increasing tendency in the R25 group compared with the R0 group (0.05 < p < 0.10), but the shear force, water loss rate and crude protein of meat had opposite results. In conclusion, rutin could not affect the growth performance and slaughter performance of goats; low levels could possibly improve meat quality.

Quality Formation of Adzuki Bean Baked: From Acrylamide to Volatiles under Microwave Heating and Drum Roasting.

Baked adzuki beans are rich in tantalizing odor and nutritional components, such as protein, dietary fiber, vitamin B, and minerals. To analyze the final quality of baked beans, the acrylamide and volatile formation of adzuki beans were investigated under the conditions of microwave baking and drum roasting. The results indicate that the acrylamide formation in baked adzuki beans obeys the exponential growth function during the baking process, where a rapid increase in acrylamide content occurs at a critical temperature and low moisture content. The critical temperature that leads to a sudden increase in acrylamide content is 116.5 °C for the moisture content of 5.6% (w.b.) in microwave baking and 91.6 °C for the moisture content of 6.1% (w.b.) in drum roasting. The microwave-baked adzuki beans had a higher formation of the kinetics of acrylamide than that of drum-roasted beans due to the microwave volumetric heating mode. The acrylamide content in baked adzuki beans had a significant correlation with their color due to the Maillard reaction. A color difference of 11.1 and 3.6 may be introduced to evaluate the starting point of the increase in acrylamide content under microwave baking and drum roasting, respectively. Heating processes, including microwave baking and drum roasting, for adzuki beans generate characteristic volatile compounds such as furan, pyrazine, ketone, alcohols, aldehydes, esters, pyrroles, sulfocompound, phenols, and pyridine. Regarding flavor formation, beans baked via drum roasting showed better flavor quality than microwave-baked beans.

Effect of Metal Substrate on Electrocatalytic Property of Palladium Nanowire Array for High Performance Ethanol Electro-Oxidation.

In this research, a high performance, ionomer-free electrocatalyst based on vertically aligned palladium (Pd) nanowire array was developed as an anode electrode toward ethanol oxidation reaction (EOR) in an alkaline environment. Using a one-step electrodeposition method, the Pd nanowires with controlled length were obtained by varying the electrodeposition current density and the synthesis time. Scanning electron microcopy (SEM), energy dispersive X-ray spectroscopy (EDS), and X-ray powder diffraction (XRD) were employed to characterize the morphology, chemical composition, and crystal structure of the Pd nanowires. The length effects of the nanowires, in the range of 0.8-4.5 µm, and various metal substrates, such as Ag, Cu, Ni, and Ti, were investigated for their electrochemical activities. The results demonstrated that Ag was the most active substrate to facilitate the ethanol oxidation reaction of the Pd nanowire array (NWA) electrocatalyst, which could be related to its good electrical conductivity. The stability test of the Pd NWA/Ag over time for EOR was also carried out, and the catalytic activity was recovered after the electrode was replaced with a new ethanol solution. Electrochemical impedance spectroscopy (EIS) measurements were performed to provide insights in the electron transfer resistance between the electrode and analyte. Gas chromatography and UV-vis spectroscopy were employed to measure the concentration of chemical species, which helped elucidate the overall reaction mechanism on the electrode surfaces.

Multisegment nanowire/nanoparticle hybrid arrays as electrochemical biosensors for simultaneous detection of antibiotics.

Antibiotics such as penicillin and tetracycline drugs are widely used in food animals to treat, control, and prevent diseases, and penicillin is approved for use to improve growth rates in pigs and poultry. However, due to the overuse of antibiotics in food and medical industry, the antimicrobial resistance is starting to show up in some developing countries. The antibiotic abuse may cause allergic reactions, resistance in microorganisms and general lowering of immunity in consumers of meat and dairy products. It is important and necessary to develop an easy, inexpensive, and quantitative sensing method to monitor and analyze the antibiotics concentration in real samples such as milk or meat. In this research, an electrochemical biosensor based on hybrid nanowire/nanoparticle array with various bio-molecular receptors was fabricated for the simultaneous detection of penicillin and tetracycline. The vertically aligned Pt-Au nanowire array has been prepared by an electrodeposition method within anodic aluminum oxide (AAO) membranes; L-cysteine was used to form a monolayer on the Au segment as the bio-receptor for tetracycline detection; electroless plating of Au nanoparticles was applied on the Pt nanowire segments, and then the penicillinase was immobilized on the Au nanoparticles using EDC/NHS cross-linker. The prepared Au(L-cysteine)-Pt(penicillinase) nanowire array electrode showed simultaneous detection ability and remarkably high sensitivity of penicillin and tetracycline, which are 41.2 µA µM-1 cm-2 for penicillin detection and 26.4 µA µM-1 cm-2 for tetracycline detection. The sensitivities of each analytes with different segment length were also investigated. Real sample tests with chicken and beef extract were conducted, which showed good recovery performance. Due to the advantages of the hybrid nanowire/nanoparticle array structure, this new sensor can serve as an enhanced platform for simultaneous detection of various bioanalytes.

Yb3+ and Yb3+/Er3+ Doping for Near-Infrared Emission and Improved Stability of CsPbCl3 Nanocrystals.

Lead halide perovskite nanocrystals (NCs) exhibit excellent tunable emissions covering the entire visible spectral region, but they do not emit near-infrared (NIR) light. We synthesized rare earth element doped CsPbCl3 NCs for NIR emission. The Yb3+ doped CsPbCl3 NCs emitted strong 986 nm NIR light; the Yb3+/Er3+ co-doped CsPbCl3 NCs emitted at 1533 nm. The total photoluminescence quantum yield (PL QY) of the CsPbCl3 NCs changed from 5.0% to 127.8% upon incorporating 2.0% Yb3+, a factor of 25.6 times enhancement. The material's stability was tested under continuous ultraviolet (365 nm) irradiation. The doped CsPbCl3 NCs exhibited a better stability than the undoped one. The PL intensity of the undoped CsPbCl3 NCs dropped to 20% of the initial value in 27 h, while the doped one took 85 h.

Treatment by ultrasound-guided local infiltration in adhesion-related abdominal pain and intractable hiccups: A case report.

RATIONALE: Abdominal pain and hiccups secondary to intra-abdominal adhesion are surgical complications that are often treated by painkillers and secondary surgeries with an unsatisfactory therapeutic effect. This study presents a new treatment method that uses ultrasound-guided local infiltration in peritoneal and abdominal wall adhesions in patients with hiccups and abdominal pain. PATIENT CONCERNS: A 62-year-old patient presented to our hospital with a history of intractable hiccups and abdominal pain for 30 years. DIAGNOSES: Her abdominal examination revealed a scar with an approximate length of 10 cm on the abdominal umbilical plane; pressing the right scar area could simultaneously induce abdominal pain and hiccups. Intraperitoneal computed tomography examination clearly demonstrated that the bowel had no obvious expansion. Ultrasonographic examination found that peritoneal motility below the normal peritoneal adhesion regions was significantly slower than in the normal regions. The diagnosis of chronic postoperative pain syndrome was clear. INTERVENTIONS: The symptoms were significantly alleviated by a successful treatment with ultrasound-guided local infiltration in the peritoneal and abdominal wall scar adhesions. OUTCOMES: After 3 stages of hospitalization and 1 year of follow-up, the patient's abdominal wall pain was relieved by approximately 80% and hiccups were relieved by approximately 70%. LESSONS: The above treatment is a useful option for managing abdominal adhesion and accompanying pain or hiccups resulting from abdominal surgery. This method could ease the psychological and economic burden of patients and improve their quality of life.

Theoretical range precision obtained by maximum likelihood estimation in laser radar compared with the Cramer-Rao bound.

The waveform fitting technique has been a prevailing method for accurate extraction of a range of objects from an observed signal. Exploration of range precision then became a significant research topic to evaluate the performance of the technique with the corruption of noise. In this paper, we derive an analytical solution of the maximum likelihood estimation for the Gaussian model as the probability density function (PDF) of the range estimator. The variance of the linear version of the PDF is consistent with the Cramer-Rao bound (CRB). Thus, the variance of the PDF is regarded as the theoretical range precision (TRP) compared with the CRB. The verification results show the TRP can perfectly describe the variance of the simulation data while the CRB provides a lower bound. At a higher signal-to-noise ratio (SNR), both the TRP and CRB have the ability to provide an accurate description of the range precision. At a lower SNR, the TRP still performs well while the CRB is too loose to bound the variance on the unbiased estimation.

Phase diagram and structural evolution of tin/indium (Sn/In) nanosolder particles: from a non-equilibrium state to an equilibrium state.

A binary system of tin/indium (Sn/In) in the form of nanoparticles was investigated for phase transitions and structural evolution at different temperatures and compositions. The Sn/In nanosolder particles in the composition range of 24-72 wt% In were synthesized by a surfactant-assisted chemical reduction method under ambient conditions. The morphology and microstructure of the as-synthesized nanoparticles were analyzed by scanning electron microscopy (SEM), high resolution transmission electron microscopy (HRTEM), selected area electron diffraction (SAED) and X-ray diffraction (XRD). HRTEM and SAED identified InSn4 and In, with some Sn being detected by XRD, but no In3Sn was observed. The differential scanning calorimetry (DSC) thermographs of the as-synthesized nanoparticles exhibited an endothermic peak at around 116 °C, which is indicative of the metastable eutectic melting of InSn4 and In. When the nanosolders were subjected to heat treatment at 50-225 °C, the equilibrium phase In3Sn appeared while Sn disappeared. The equilibrium state was effectively attained at 225 °C. A Tammann plot of the DSC data of the as-synthesized nanoparticles indicated that the metastable eutectic composition is about 62% In, while that of the DSC data of the 225 °C heat-treated nanoparticles yielded a eutectic composition of 54% In, which confirmed the attainment of the equilibrium state at 225 °C. The phase boundaries estimated from the DSC data of heat-treated Sn/In nanosolder particles matched well with those in the established Sn-In equilibrium phase diagram. The phase transition behavior of Sn/In nanosolders leads to a new understanding of binary alloy particles at the nanoscale, and provides important information for their low temperature soldering processing and applications.

Polycyclopentene-Crystal-Decorated Carbon Nanotubes by Convenient Large-Scale In Situ Polymerization and their Lotus-Leaf-Like Superhydrophobic Films.

In situ Pd-catalyzed cyclopentene polymerization in the presence of multi-walled carbon nanotubes (MWCNTs) is demonstrated to effectively render, on a large scale, polycyclopentene-crystal-decorated MWCNTs. Controlling the catalyst loading and/or time in the polymerization offers a convenient tuning of the polymer content and the morphology of the decorated MWCNTs. Appealingly, films made of the decorated carbon nanotubes through simple vacuum filtration show the characteristic lotus-leaf-like superhydrophobicity with high water contact angle (>150°), low contact angle hysteresis (<10°), and low water adhesion, while being electrically conductive. This is the first demonstration of the direct fabrication of lotus-leaf-like superhydrophobic films with solution-grown polymer-crystal-decorated carbon nanotubes.

Rapid degradation of azo dye methyl orange using hollow cobalt nanoparticles.

A rapid and efficient method for methyl orange degradation using hollow cobalt (Co) nanoparticles is reported. Hollow Co nanoparticles were fabricated by a galvanic replacement reaction using aluminum (Al) nanoparticles as the template material. The methyl orange degradation characteristics were investigated by measuring the time dependent UV-Vis absorption of the dye solution, which showed a very fast degradation rate under acidic conditions. At an initial methyl orange concentration of 100 mg/L (pH = 2.5) and Co nanoparticle dosage of 0.5 g/L, the azo dye degradation efficiency reached up to 99% within 4 min, and the degradation constant rate was up to 2.444 min(-1), which is the highest value among other studies. A comparison of the decolorization rates at similar conditions with several other azo dyes, including Congo red, Amaranth, and Orange G, showed that the dye with a simpler structure and lower molecular mass decolorized considerably faster than the ones having a more complicated structure (higher molecular mass). The methyl orange degradation was also conducted using hollow nickel (Ni) nanoparticles and commercially available solid spherical Co and Ni nanoparticles. The results showed that Co-based nanoparticles outperformed Ni-based nanoparticles, with the hollow Co nanoparticles exhibiting the fastest degradation rate. Using the hollow Co nanoparticles is a very promising approach for the remediation of methyl orange dye containing wastewater due to the fast degradation rate and high degradation efficiency. In addition, these hollow Co nanoparticles are easily recycled because of their magnetic property.

Effects of Nanowire Length and Surface Roughness on the Electrochemical Sensor Properties of Nafion-Free, Vertically Aligned Pt Nanowire Array Electrodes.

In this paper, vertically aligned Pt nanowire arrays (PtNWA) with different lengths and surface roughnesses were fabricated and their electrochemical performance toward hydrogen peroxide (H2O2) detection was studied. The nanowire arrays were synthesized by electroplating Pt in nanopores of anodic aluminum oxide (AAO) template. Different parameters, such as current density and deposition time, were precisely controlled to synthesize nanowires with different surface roughnesses and various lengths from 3 µm to 12 µm. The PtNWA electrodes showed better performance than the conventional electrodes modified by Pt nanowires randomly dispersed on the electrode surface. The results indicate that both the length and surface roughness can affect the sensing performance of vertically aligned Pt nanowire array electrodes. Generally, longer nanowires with rougher surfaces showed better electrochemical sensing performance. The 12 µm rough surface PtNWA presented the largest sensitivity (654 µA·mM⁻¹·cm⁻²) among all the nanowires studied, and showed a limit of detection of 2.4 µM. The 12 µm rough surface PtNWA electrode also showed good anti-interference property from chemicals that are typically present in the biological samples such as ascorbic, uric acid, citric acid, and glucose. The sensing performance in real samples (river water) was tested and good recovery was observed. These Nafion-free, vertically aligned Pt nanowires with surface roughness control show great promise as versatile electrochemical sensors and biosensors.

In situ visualization of metallurgical reactions in nanoscale Cu/Sn diffusion couples.

The Cu-Sn metallurgical soldering reaction in two-segmented Cu-Sn nanowires is studied by in situ transmission electron microscopy. By varying the relative lengths of Cu and Sn segments, we show that the metallurgical reaction results in a Cu-Sn solid solution for small Sn/Cu length ratio while Cu-Sn intermetallic compounds (IMCs) for larger Sn/Cu length ratios. Upon heating the nanowires to ∼500 °C, two phase transformation pathways occur, η-Cu6Sn5 → ε-Cu3Sn → δ-Cu41Sn11 for nanowires with a long Cu segment and η-Cu6Sn5 → ε-Cu3Sn → γ-Cu3Sn with a short Cu segment. The evolution of Kirkendall voids in the nanowires demonstrates that Cu diffuses faster than Sn in IMCs. Void growth results in the nanowire breakage that shuts off the inter-diffusion of Cu and Sn and thus leads to changes in the phase transformation pathway in the IMCs.

Synthesis of surface roughed Pt nanowires and their application as electrochemical sensors for hydrogen peroxide detection.

In this paper, platinum nanowires with roughed surface textures were fabricated by a galvanostatic electrodeposition method for electrochemical sensors toward hydrogen peroxide detection. The electrochemical behavior of the glassy carbon electrode modified with these nanowires has been studied for oxidation of hydrogen peroxide by using cyclic voltammetry and amperometry in phosphate buffer solution. Surface roughness was found to enhance the sensitivity of the Pt nanowire based electrochemical sensor towards H2O2. The Pt nanowires with rough surfaces displayed higher electrocatalytic response compared to nanowires with smooth surfaces, with a sensitivity of 171 µA mM(-1) cm(-2), and linear dynamic range up to 35 mM. The nanowire concentration effect on the sensing behavior was investigated with the best sensitivity output found at a nanowire concentration of roughly 8.6 x 10(7) number of nanowires/cm2. The new sensor also showed good anti-interference property and exhibited high accuracy when a real water sample containing H2O2 was measured.

Paclitaxel/sirolimus combination coated drug-eluting stent: in vitro and in vivo drug release studies.

Paclitaxel and sirolimus are the two major drugs for the treatment of coronary arterial disease in current drug-eluting stents. The two drugs can effectively inhibit the in-stent restenosis through their independent pathways and show synergistic effect in preventing tumor tissue growth. We hypothesize that the combination of the two drugs in a drug-eluting stent (DES) can also effectively suppress the neointima growth in the stented artery. The present work was focused on the investigation of paclitaxel/sirolimus combination release profiles from a novel biodegradable polymer (poly (D, L-lactide-co-glycolide)/amorphous calcium phosphate, PLGA/ACP) coated stent both in vitro and in vivo. For the in vitro, the drug releasing profiles were characterized by measuring the drug concentration in a drug release medium (Dulbecco's phosphate buffered saline, DPBS, pH 7.4) at predetermined time points. For the in vivo, a rat aorta stenting model was employed. The results showed that both paclitaxel and sirolimus had a two-phase release profile both in vitro and in vivo, which is similar to the drug release profile of their individual coated DESs, and there is no evident of interference between two drugs. The data suggest that paclitaxel and sirolimus can be combined pharmacokinetically in a DES for the treatment of coronary arterial diseases.

Formation of PbSe/CdSe Core/Shell Nanocrystals for Stable Near-Infrared High Photoluminescence Emission.

PbSe/CdSe core/shell nanocrystals with quantum yield of 70% were obtained by the "successive ion layer adsorption and reaction" technology in solution. The thickness of the CdSe shell was exactly controlled. A series of spectral red shifts with the CdSe shell growth were observed, which was attributed to the combined effect of the surface polarization and the expansion of carriers' wavefunctions. The stability of PbSe nanocrystals was tremendously improved with CdSe shells.

Nano-soldering of magnetically aligned three-dimensional nanowire networks.

It is extremely challenging to fabricate 3D integrated nanostructures and hybrid nanoelectronic devices. In this paper, we report a simple and efficient method to simultaneously assemble and solder nanowires into ordered 3D and electrically conductive nanowire networks. Nano-solders such as tin were fabricated onto both ends of multi-segmented nanowires by a template-assisted electrodeposition method. These nanowires were then self-assembled and soldered into large-scale 3D network structures by magnetic field assisted assembly in a liquid medium with a high boiling point. The formation of junctions/interconnects between the nanowires and the scale of the assembly were dependent on the solder reflow temperature and the strength of the magnetic field. The size of the assembled nanowire networks ranged from tens of microns to millimeters. The electrical characteristics of the 3D nanowire networks were measured by regular current-voltage (I-V) measurements using a probe station with micropositioners. Nano-solders, when combined with assembling techniques, can be used to efficiently connect and join nanowires with low contact resistance, which are very well suited for sensor integration as well as nanoelectronic device fabrication.