THUMPD3-AS1 inhibits ovarian cancer cell apoptosis through the miR-320d/ARF1 axis.

Ovarian cancer is one of the most common gynecologic malignancies that has a poor prognosis. THUMPD3-AS1 is an oncogenic long noncoding RNA (lncRNA) in several cancers. Moreover, miR-320d is downregulated and inhibited proliferation in ovarian cancer cells, whereas ARF1 was upregulated and promoted the malignant progression in epithelial ovarian cancer. Nevertheless, the role of THUMPD3-AS1 in ovarian cancer and the underlying mechanism has yet to be elucidated. Human normal ovarian epithelial cells (IOSE80) and ovarian cancer cell lines (CAVO3, A2780, SKOV3, OVCAR3, and HEY) were adopted for in vitro experiments. The functional roles of THUMPD3-AS1 in cell viability and apoptosis were determined using CCK-8, flow cytometry, and TUNEL assays. Western blot was performed to assess the protein levels of ARF1, Bax, Bcl-2, and caspase 3, whereas RT-qPCR was applied to measure ARF1 mRNA, THUMPD3-AS1, and miR-320d levels. The targeting relationship between miR-320d and THUMPD3-AS1 or ARF1 was validated with dual luciferase assay. THUMPD3-AS1 and ARF1 were highly expressed in ovarian cancer cells, whereas miR-320d level was lowly expressed. THUMPD3-AS1 knockdown was able to repress cell viability and accelerate apoptosis of OVCAR3 and SKOV3 cells. Also, THUMPD3-AS1 acted as a sponge of miR-320d, preventing the degradation of ARF1. MiR-320d downregulation reversed the tumor suppressive function induced by THUMPD3-AS1 depletion. Additionally, miR-320d overexpression inhibited ovarian cancer cell viability and accelerated apoptosis, which was overturned by overexpression of ARF1. THUMPD3-AS1 inhibited ovarian cancer cell apoptosis by modulation of miR-320d/ARF1 axis. The discoveries might provide a prospective target for ovarian cancer treatment.

Dynamic modulation of nodulation factor receptor levels by phosphorylation-mediated functional switch of a RING-type E3 ligase during legume nodulation.

The precise control of receptor levels is crucial for initiating cellular signaling transduction in response to specific ligands; however, such mechanisms regulating nodulation factor (NF) receptor (NFR)-mediated perception of NFs to establish symbiosis remain unclear. In this study, we unveil the pivotal role of the NFR-interacting RING-type E3 ligase 1 (NIRE1) in regulating NFR1/NFR5 homeostasis to optimize rhizobial infection and nodule development in Lotus japonicus. We demonstrated that NIRE1 has a dual function in this regulatory process. It associates with both NFR1 and NFR5, facilitating their degradation through K48-linked polyubiquitination before rhizobial inoculation. However, following rhizobial inoculation, NFR1 phosphorylates NIRE1 at a conserved residue, Tyr-109, inducing a functional switch in NIRE1, which enables NIRE1 to mediate K63-linked polyubiquitination, thereby stabilizing NFR1/NFR5 in infected root cells. The introduction of phospho-dead NIRE1Y109F leads to delayed nodule development, underscoring the significance of phosphorylation at Tyr-109 in orchestrating symbiotic processes. Conversely, expression of the phospho-mimic NIRE1Y109E results in the formation of spontaneous nodules in L. japonicus, further emphasizing the critical role of the phosphorylation-dependent functional switch in NIRE1. In summary, these findings uncover a fine-tuned symbiotic mechanism that a single E3 ligase could undergo a phosphorylation-dependent functional switch to dynamically and precisely regulate NF receptor protein levels.

Earthworm gut digestion drives the transfer behavior of antibiotic resistance genes in layers of extracellular polymeric substances during vermicomposting of dewatered sludge.

Gut digestion by earthworms (GDE) is a crucial step in vermicomposting, affecting the fate of antibiotic resistance genes (ARGs) in vermicompost sludge. The extracellular polymeric substance (EPS) matrix of sludge is an important space for ARG transfer. However, the effect of GDE on EPS-associated ARGs remains unclear. Therefore, this study explored the role of GDE in driving the transfer of ARGs within different EPS layers in sludge. For this, the changes in intracellular ARGs and EPS-associated ARGs in sludge were analyzed after 5 days of the GDE process. The results showed that after the GDE process, both nitrate and dissolved organic carbon significantly increased in all EPS layers of sludge, while the proteins and polysaccharides only enhanced in soluble and loosely bound EPS of sludge. In addition, a 7.0% decrease in bacterial diversity was recorded after the GDE process, with a functional bacterial community structure emerging. Moreover, the absolute abundance of total ARGs and mobile genetic elements decreased by 90.71% and 61.83%, respectively, after the GDE process. Intracellular ARGs decreased by 92.1%, while EPS-associated ARGs increased by 4.9%, indicative of intracellular ARG translocation into the EPS during the GDE process. Notably, the ARGs exhibited significant enrichment in both the soluble and loosely bound EPS, whereas they were reduced in the tightly bound EPS. The structural equation modeling revealed that the GDE process effectively mitigated the ARG dissemination risk by modulating both the EPS structure and microenvironment, with the organic structure representing a primary factor influencing ARGs in the EPS.

Enhancing CO2 Electroreduction to C2 Products on Metal-Nitrogen Sites by Regulating H2O Dissociation.

Water dissociation remarkably affects the CO2 reduction to CO and HCOOH, but whether it is effective for two-carbon product formation on M-Nx-containing catalysts is still ambiguous. Herein, by using a fluorinated metal phthalocyanine (MPc-F) as the M-N4-based model electrocatalyst, experimental and theoretical results reveal that the H2O-dissociation-induced active H species decrease the overpotential of the *CO hydrogenation to *CHO and facilitate the C-C coupling between *CHO and neighboring CO. Such an effect is strengthened by an increase in the *CO binding strength on the metal center. By introducing CuPc as the H2O dissociation catalyst into MPc-F (MPc-F/CuPc) to accurately regulate the H2O dissociation, the faradic efficiency of C2 products on FePc-F/CuPc and MnPc-F/CuPc increases from 0% (FePc-F and MnPc-F) to 26 and 36%, respectively. This work develops a novel strategy for enhancing the selectivity of M-Nx-containing catalysts to C2 products and reveals the correlation between H2O dissociation and C2 product formation.

Ultrasound­guided erector spinae plane block in posterior lumbar surgery (Review).

The erector spinae plane block (ESPB) is a novel fascial planar block technique, which is used to reduce postoperative pain in several surgical procedures, including breast, thoracic, spine and hip surgery. Due to its recognizable anatomy and low complication rate, the application of ESPB has been significantly increased. However, it is rarely used in clinical practice for postoperative analgesia after posterior lumbar spine surgery, while the choice of adjuvant drugs, block levels and drug doses remain controversial. Based on the current literature review, ropivacaine and dexmedetomidine could be considered as the best available drug combination. The present review aimed to analyze the currently available clinical evidence and summarize the benefits and challenges of ESPB in spinal surgery, thus providing novel insights into the application of ESPB in the postoperative management of posterior lumbar surgery.

Predictive Value of 5-Methoxytryptophan on Long-Term Clinical Outcome after PCI in Patients with Acute Myocardial Infarction-a Prospective Cohort Study.

BACKGROUND: In recent years, 5-Methoxytryptophan (5-MTP) has been identified as an endothelial factor with vaso-protective and anti-inflammatory properties. METHODS: In this prospective cohort study, a total of 407 patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI) successfully were enrolled. A 1-year follow-up Kaplan-Meier survival analysis was used for evaluating the correlation between 5-MTP and major adverse cardiovascular event (MACE) while Cox proportional-hazards regression was used to identify predictive values of 5-MTP on MACE after AMI. RESULTS: Increased 5-MTP level led to a significant downtrend in the incidence of MACE (All Log-rank p < 0.05). Thus, a high baseline 5-MTP could reduce the 1-year incidence of MACE (HR = 0.33, 95%Cl 0.17-0.64, p = 0.001) and heart failure (HF) (HR = 0.28, 95% Cl 0.13-0.62, p = 0.002). Subgroup analysis indicated the predictive value of 5-MTP was more significant in patients aged ≤ 65 years and those with higher baseline NT-proBNP, T2DM, STEMI, and baseline HF with preserved LVEF (HFpEF) characteristics. CONCLUSIONS: Plasma 5-MTP is an independent and protective early biomarker for 1-year MACE and HF events in patients with AMI, especially in younger patients and those with T2DM, STEMI, and baseline HFpEF characteristics.

[Characteristics of Microorganisms and Antibiotic Resistance Genes of the Riparian Soil in the Lanzhou Section of the Yellow River].

Riparian soil is a critical area of watersheds. The characteristics of biological contaminants in riparian soil affect the pollution control of the watershed water environment. Thus, the microbial community structure, antibiotic resistance genes (ARGs), and mobile genetic elements (MGEs) in the riparian soil of the Lanzhou section of the Yellow River were investigated by analyzing the characteristics of soil samples collected from farmland, mountains, and industrial land. The results showed that the Proteobacteria, Bacteroidetes, and Actinobacteria were the dominant phyla in the riparian soil of Lanzhou section of the Yellow River. The microbial structure in the riparian soil was significantly correlated with the land use type (P < 0.05). The α diversity index of bacterial communities in land types was in the order of farmland > mountain > industry. Sulfonamide-typed ARGs were the most dominant genes in the soil of the Lanzhou section of the Yellow River Basin, among which the sul1 gene had the highest abundance, 20-36 000 times that of other detected ARGs. Moreover, the total absolute abundance of ARGs in industrial soil was the highest. Principal coordinate analysis (PCoA) displayed that the ARGs characteristics had a significant correlation with land types (P < 0.05), and intl1 and tnpA-04 drove the diffuseness of sulfonamide and tetracycline ARGs, respectively. Redundancy analysis (RDA) demonstrated that the content of inorganic salt ions and total phosphorus in the soil of the riparian zone of the Yellow River Lanzhou section were the main environmental factors, modifying the distribution of the microbial structure. Halobacterota and Acidobacteriota were the main microflora that drove the structural change in ARGs.

Phenotype-considered kinematically aligned total knee arthroplasty for windswept-deformity-associated osteoarthritis: surgical strategy and clinical outcomes.

BACKGROUND: Windswept deformity (WSD) in relation to advanced osteoarthritis (OA) presents a significant surgical challenge in total knee arthroplasty (TKA). The primary goal of this study is to investigate the Prevalance of WSD associated osteoarthritis who have undergone total knee arthroplasty. The secondary goal is to explore the causes of WSD and its association with spinal deformity or leg length discrepancy in these patients. Finally, we evaluate the surgical outcomes of phenotype-considered kinematically aligned TKA (KA-TKA) in treating patients with WSD. METHODS: A review was conducted on data from 40 knees of 33 WSD patients who underwent phenotype-considered KA-TKA from August 2016 to December 2020. Patient demographics, associated diseases, preoperative and postoperative knee alignment angles, range of motion (ROM), Oxford Knee Score (OKS), and Knee Society Score (KSS) were collected and analyzed. Subgroup analysis for comparing the results between valgus and varus knees were also performed. RESULTS: Within the studied cohort of WSD patients, a substantial 64% displayed concomitant coronal spinal imbalance and 21% evidenced leg length discrepancy. Postoperative improvements were notable in knee alignments, ROM, OKS, and KSS following the application of the phenotype-considered KA-TKA approach. There were significant differences in the knee alignment angles, including mHKA, LDFA, and MPTA, between the valgus and varus side of knees (P = 0.018). However, no statistically significant difference were observed in the functional scores, comprising ROM, OKS, and KSS, between valgus and varus knees. CONCLUSIONS: A high percentage of patients with WSD exhibited coronal spinal imbalance and leg length discrepancy. Phenotype-considered KA-TKA effectively provided alignment targets for the treatment of both varus and valgus knees in patients with WSD, achieving excellent short-term outcomes and acceptable knee alignment.

Bacterial dispersal enhances the elimination of active fecal coliforms during vermicomposting of fruit and vegetable wastes: The overlooked role of earthworm mucus.

Earthworms play a pivotal role in the elimination of fecal coliforms during vermicomposting of fruit and vegetable waste (FVWs). However, the specific mechanisms underlying the action of earthworm mucus remain unclear. This study investigated the mechanisms of fecal coliform reduction related to earthworm mucus during FVWs vermicomposting by comparing treatments with and without earthworms. The results show that the secretion of earthworm mucus decreased by 13.93 % during the startup phase, but significantly (P < 0.001) increased by 57.80 % during the degradation phase. Compared to the control without earthworms, vermicomposting led to a significant (P < 0.05) 1.22 -fold increase in the population of active bacteria, with a strong positive correlation between mucus characteristics and dominant bacterial phyla. As the dominant fecal coliforms, Escherichia coli and Klebsiella pneumoniae significantly (P < 0.05) declined by 86.20 % and 93.38 %, respectively, in the vermi-reactor relative to the control. Bacterial dispersal limitation served as a key factor constraining the elimination of E. coli (r = 0.73, P < 0.01) and K. pneumoniae (r = 0.77, P < 0.001) during vermicomposting. This study suggests that earthworm mucus increases the active bacterial abundance and cooperation by weakening the bacterial dispersal limitation, thus intensifying competition and antagonism between fecal coliforms and other bacteria.

Toward Unified AI Drug Discovery with Multimodal Knowledge.

Background: In real-world drug discovery, human experts typically grasp molecular knowledge of drugs and proteins from multimodal sources including molecular structures, structured knowledge from knowledge bases, and unstructured knowledge from biomedical literature. Existing multimodal approaches in AI drug discovery integrate either structured or unstructured knowledge independently, which compromises the holistic understanding of biomolecules. Besides, they fail to address the missing modality problem, where multimodal information is missing for novel drugs and proteins. Methods: In this work, we present KEDD, a unified, end-to-end deep learning framework that jointly incorporates both structured and unstructured knowledge for vast AI drug discovery tasks. The framework first incorporates independent representation learning models to extract the underlying characteristics from each modality. Then, it applies a feature fusion technique to calculate the prediction results. To mitigate the missing modality problem, we leverage sparse attention and a modality masking technique to reconstruct the missing features based on top relevant molecules. Results: Benefiting from structured and unstructured knowledge, our framework achieves a deeper understanding of biomolecules. KEDD outperforms state-of-the-art models by an average of 5.2% on drug-target interaction prediction, 2.6% on drug property prediction, 1.2% on drug-drug interaction prediction, and 4.1% on protein-protein interaction prediction. Through qualitative analysis, we reveal KEDD's promising potential in assisting real-world applications. Conclusions: By incorporating biomolecular expertise from multimodal knowledge, KEDD bears promise in accelerating drug discovery.

A pathogenesis-related protein, PRP1, negatively regulates root nodule symbiosis in Lotus japonicus.

The legume-rhizobium symbiosis represents a unique model within the realm of plant-microbe interactions. Unlike typical cases of pathogenic invasion, the infection of rhizobia and their residence within symbiotic cells do not elicit a noticeable immune response in plants. Nevertheless, there is still much to uncover regarding the mechanisms through which plant immunity influences rhizobial symbiosis. In this study, we identify an important player in this intricate interplay: Lotus japonicus PRP1, which serves as a positive regulator of plant immunity but also exhibits the capacity to decrease rhizobial colonization and nitrogen fixation within nodules. The PRP1 gene encodes an uncharacterized protein and is named Pathogenesis-Related Protein1, owing to its orthologue in Arabidopsis thaliana, a pathogenesis-related family protein (At1g78780). The PRP1 gene displays high expression levels in nodules compared to other tissues. We observed an increase in rhizobium infection in the L. japonicus prp1 mutants, whereas PRP1-overexpressing plants exhibited a reduction in rhizobium infection compared to control plants. Intriguingly, L. japonicus prp1 mutants produced nodules with a pinker colour compared to wild-type controls, accompanied by elevated levels of leghaemoglobin and an increased proportion of infected cells within the prp1 nodules. The transcription factor Nodule Inception (NIN) can directly bind to the PRP1 promoter, activating PRP1 gene expression. Furthermore, we found that PRP1 is a positive mediator of innate immunity in plants. In summary, our study provides clear evidence of the intricate relationship between plant immunity and symbiosis. PRP1, acting as a positive regulator of plant immunity, simultaneously exerts suppressive effects on rhizobial infection and colonization within nodules.

Spatial Contraction Based on Velocity Variation for Natural Walking in Virtual Reality.

Virtual Reality (VR) offers an immersive 3D digital environment, but enabling natural walking sensations without the constraints of physical space remains a technological challenge. Previous VR locomotion methods, including game controller, teleportation, treadmills, walking-in-place, and redirected walking (RDW), have made strides towards overcoming this challenge. However, these methods also face limitations such as possible unnaturalness, additional hardware requirements, or motion sickness risks. This paper introduces "Spatial Contraction (SC)", an innovative VR locomotion method inspired by the phenomenon of Lorentz contraction in Special Relativity. Similar to the Lorentz contraction, our SC contracts the virtual space along the user's velocity direction in response to velocity variation. The virtual space contracts more when the user's speed is high, whereas minimal or no contraction happens at low speeds. We provide a virtual space transformation method for spatial contraction and optimize the user experience in smoothness and stability. Through SC, VR users can effectively traverse a longer virtual distance with a shorter physical walking. Different from locomotion gains, the spatial contraction effect is observable by the user and aligns with their intentions, so there is no inconsistency between the user's proprioception and visual perception. SC is a general locomotion method that has no special requirements for VR scenes. The experimental results of our live user studies in various virtual scenarios demonstrate that SC has a significant effect in reducing both the number of resets and the physical walking distance users need to cover. Furthermore, experiments have also demonstrated that SC has the potential for integration with existing locomotion techniques such as RDW.

Understanding AAV vector immunogenicity: from particle to patient.

Gene therapy holds promise for patients with inherited monogenic disorders, cancer, and rare genetic diseases. Naturally occurring adeno-associated virus (AAV) offers a well-suited vehicle for clinical gene transfer due to its lack of significant clinical pathogenicity and amenability to be engineered to deliver therapeutic transgenes in a variety of cell types for long-term sustained expression. AAV has been bioengineered to produce recombinant AAV (rAAV) vectors for many gene therapies that are approved or in late-stage development. However, ongoing challenges hamper wider use of rAAV vector-mediated therapies. These include immunity against rAAV vectors, limited transgene packaging capacity, sub-optimal tissue transduction, potential risks of insertional mutagenesis and vector shedding. This review focuses on aspects of immunity against rAAV, mediated by anti-AAV neutralizing antibodies (NAbs) arising after natural exposure to AAVs or after rAAV vector administration. We provide an in-depth analysis of factors determining AAV seroprevalence and examine clinical approaches to managing anti-AAV NAbs pre- and post-vector administration. Methodologies used to quantify anti-AAV NAb levels and strategies to overcome pre-existing AAV immunity are also discussed. The broad adoption of rAAV vector-mediated gene therapies will require wider clinical appreciation of their current limitations and further research to mitigate their impact.

Revealing a Double-Volcano-Like Structure-Activity Relationship for Substitution-Functionalized Metal-Phthalocyanine Catalysts toward Electrochemical CO2 Reduction.

Electron-donating/-withdrawing groups (EDGs/EWGs) substitution is widely used to regulate the catalytic performance of transition-metal phthalocyanine (MPc) toward electrochemical CO2 reduction, but the corresponding structure-activity relationships and regulation mechanisms are still ambiguous. Herein, by investigating a series of substitution-functionalized MPc (MPc-X), this work reveals a double-volcano-like relationship between the electron-donating/-withdrawing abilities of the substituents and the catalytic activities of MPc-X. The weak-EDG/-EWG substitution enhances whereas the strong-EDG/-EWG substitution mostly lowers the CO selectivity of MPc. Experimental and calculation results demonstrate that the electronic properties of the substituents influence the symmetry and energy of the highest occupied molecular orbitals of MPc-X, which in turn determine the CO2 adsorption/activation and lead to diverse CO2 reduction pathways on the EWG or EDG substituted MPc via different CO2 adsorption modes. This work provides mechanism insights that could be guidance for the design and regulation of molecular catalysts.

Wnt10b regulates osteogenesis of adipose-derived stem cells through Wnt/ß-catenin signalling pathway in osteoporosis.

Our previous finding revealed that the Wnt10b RNA expression of osteoporotic adipose-derived stem cells (OP-ASCs) with impaired osteogenic capacity was significantly reduced than that of ASCs. There are no ideas that the relationship between the OP-ASCs' impaired osteogenic potential and Wnt10b expression. This study aimed to indicate the potential molecular mechanisms and functional role of Wnt10b in OP-ASCs, as well as to investigate a potential application to reverse the OP-ASCs' impaired osteogenic differentiation potential. The OP-ASCs and ASCs were harvested from the inguinal fat of osteoporosis (OP) mice with bilateral ovariectomy (OVX) and normal mice. qPCR and WB were used to detect the different levels of the expression of the Wnt10b RNA in both OP-ASCs and ASCs. Lentiviral-mediated regulation of Wnt10b expression was employed for OP-ASCs, and the detection of the expression levels of key molecules in the Wnt signalling pathway and key osteogenic factors was performed through qPCR and WB in vitro experiments. The capacity of OP-ASCs to osteogenesis was determined using alizarin red staining. Lastly, the repair effect of the BCP scaffolds incorporating modified OP-ASCs on the critical-sized calvarial defects (CSCDs) in OP mice was scanned and detected by micro-computed tomography, haematoxylin and eosin staining, Masson's trichrome staining and immunohistochemistry. First, we discovered that both the RNA and protein expression levels of Wnt10b were significantly lower in OP-ASCs than that in ASCs. In vitro experiments, upregulation of Wnt10b could activate the Wnt signalling pathway, and increase expression of ß-catenin, Lef1, Runx2 and osteopontin (Opn), thereby enhancing the osteogenic ability of OP-ASCs. In addition, the OP-ASCs with Wnt10b-overexpressing could promote the repair of CSCD in osteoporotic mice with increasing new bone volume, bone mineral density, and increased expression of Opn in new bone in vivo. Taken together, overexpression of Wnt10b could partially facilitate the differentiation of OP-ASCs towards osteogenesis and accelerated the healing of bone defects by activating the Wnt/ß-catenin signalling pathway in vitro and in vivo experiments. This study confirmed the important role of Wnt10b in regulating the osteogenic differentiation capability of OP-ASCs and indicated Wnt10b could be a potential therapeutic target for reversing the impaired osteogenic capabilities of OP-ASCs to therapy bone defects of OP patients.

Exogenous mobile genetic elements and their associated integrons drive the enrichment of antibiotic-resistant genes in the river of a valley basin city (Lanzhou, China).

River is a unique source of drinking water in valley-type cities, affecting local urban development and human lifestyles. However, the key driving factors for dissemination of antibiotic-resistant genes (ARGs) in valley-type urban environments remain unclear. This study aimed to investigate the distribution of ARGs in the Yellow River and to clarify the driving factors of ARGs in a typical valley basin city (Lanzhou, China). The seven selected ARGs with higher abundances including tetracycline resistance genes (tetM, tetX), macrolide resistance genes (ermB, ermF, ereA), and sulfonamide resistance genes (sul1, sul2) were detected. The results showed that the total absolute abundance of all the selected ARGs varied from 9.97 × 1012 to 1.04 × 1015 copies/L in the water body, with higher abundances in the wet season, relative to the dry season. Among these, sulfonamide resistance genes (sul1, sul2) displayed the highest absolute abundance in the river and soil. The ARGs and mobile genetic elements (MGEs) were significantly correlated with bacterial abundance, dissolved organic carbon (DOC), ammonia nitrogen (NH4+), and total nitrogen (TN) levels in the water environment (Mantel test, P < 0.01). Structural equation modeling revealed the direct input of point-source and nonpoint-source ARGs in this area contributed less to the overall level of the ARGs in the water. Among the multiple drivers, the MGEs derived from wastewater treatment plant and anthropogenic nonpoint area positively and directly affected the ARG profiles in water (P < 0.01), rather than the factors of bacterial abundance and physicochemical properties. According to this study, the exogenous MGEs from anthropogenic activities are the main driver for the enrichment of ARGs in the valley-type urban river environment.

A Retrospective Comparison of Clinical Efficacy between Multimodal Analgesia and Patient-Controlled Epidural Analgesia in Patients Undergoing Total Knee Arthroplasty.

Background and Objectives: Adequate pain management during early rehabilitation is mandatory for improving the outcomes of patients undergoing total knee arthroplasty (TKA). Conventional pain management, mainly comprising opioids and epidural analgesia, may result in certain adverse effects such as dizziness, nausea, and motor blockade. We proposed a multimodal analgesic (MA) strategy involving the use of peripheral nerve block (NB), periarticular injection (PAI), and intravenous patient-controlled analgesia (IVPCA). This study compared the clinical efficacy and adverse effects of the proposed MA strategy and patient-controlled epidural analgesia (PCEA). Materials and Methods: We enrolled 118 patients who underwent TKA under spinal anesthesia. The patients followed either the MA protocol or received PCEA after surgery. The analgesic effect was examined using a numerical rating scale (NRS). The adverse effects experienced by the patients were recorded. Results: A lower proportion of patients in the MA group experienced motor blockade (6.45% vs. 22.98%) compared to those in the PCEA group on the first postoperative day. Furthermore, a lower proportion of patients in the MA group experienced numbness (18.52% vs. 43.33%) than those in the PCEA group on the first postoperative day. Conclusions: The MA strategy can be recommended for reducing the occurrence of motor blockade and numbness in patients following TKA. Therefore, the MA strategy ensures early rehabilitation while maintaining adequate pain relief.

Genetic newborn screening and digital technologies: A project protocol based on a dual approach to shorten the rare diseases diagnostic path in Europe.

Since 72% of rare diseases are genetic in origin and mostly paediatrics, genetic newborn screening represents a diagnostic "window of opportunity". Therefore, many gNBS initiatives started in different European countries. Screen4Care is a research project, which resulted of a joint effort between the European Union Commission and the European Federation of Pharmaceutical Industries and Associations. It focuses on genetic newborn screening and artificial intelligence-based tools which will be applied to a large European population of about 25.000 infants. The neonatal screening strategy will be based on targeted sequencing, while whole genome sequencing will be offered to all enrolled infants who may show early symptoms but have resulted negative at the targeted sequencing-based newborn screening. We will leverage artificial intelligence-based algorithms to identify patients using Electronic Health Records (EHR) and to build a repository "symptom checkers" for patients and healthcare providers. S4C will design an equitable, ethical, and sustainable framework for genetic newborn screening and new digital tools, corroborated by a large workout where legal, ethical, and social complexities will be addressed with the intent of making the framework highly and flexibly translatable into the diverse European health systems.

Cis-trans isomerization of peptoid residues in the collagen triple-helix.

Cis-peptide bonds are rare in proteins, and building blocks less favorable to the trans-conformer have been considered destabilizing. Although proline tolerates the cis-conformer modestly among all amino acids, for collagen, the most prevalent proline-abundant protein, all peptide bonds must be trans to form its hallmark triple-helix structure. Here, using host-guest collagen mimetic peptides (CMPs), we discover that surprisingly, even the cis-enforcing peptoid residues (N-substituted glycines) form stable triple-helices. Our interrogations establish that these peptoid residues entropically stabilize the triple-helix by pre-organizing individual peptides into a polyproline-II helix. Moreover, noting that the cis-demanding peptoid residues drastically reduce the folding rate, we design a CMP whose triple-helix formation can be controlled by peptoid cis-trans isomerization, enabling direct targeting of fibrotic remodeling in myocardial infarction in vivo. These findings elucidate the principles of peptoid cis-trans isomerization in protein folding and showcase the exploitation of cis-amide-favoring residues in building programmable and functional peptidomimetics.

Optimal real-time power dispatch of power grid with wind energy forecasting under extreme weather.

With breakthroughs in the power electronics industry, the stability and rapid power regulation of wind power generation have been improved. Its power generation technology is becoming more and more mature. However, there are still weaknesses in the operation and control of power systems under the influence of extreme weather events, especially in real-time power dispatch. To optimally distribute the power of the regulation resources in a more stable manner, a wind energy forecasting-based power dispatch model with time-control intervals optimization is proposed. In this model, the outage of the wind energy under extreme weather is analyzed by an autoregressive integrated moving average model (ARIMA). Additionally, the other regulation resources are used to balance the corresponding wind power drop and power mismatch. Meanwhile, an algorithm names weighted mean of vectors (INFO) is employed to solve the real-time power dispatch and minimize the power deviation between the power command and real output. Lastly, the performance of the proposed optimal real-time power dispatch is executed in a simulation model with ten regulation resources. The simulation tests show that the combination of ARIMA and INFO can effectively improve the power control performance of the PD-WEF system.