High-resolution short-term prediction of the COVID-19 epidemic based on spatial-temporal model modified by historical meteorological data.

In the global challenge of Coronavirus disease 2019 (COVID-19) pandemic, accurate prediction of daily new cases is crucial for epidemic prevention and socioeconomic planning. In contrast to traditional local, one-dimensional time-series data-based infection models, the study introduces an innovative approach by formulating the short-term prediction problem of new cases in a region as multidimensional, gridded time series for both input and prediction targets. A spatial-temporal depth prediction model for COVID-19 (ConvLSTM) is presented, and further ConvLSTM by integrating historical meteorological factors (Meteor-ConvLSTM) is refined, considering the influence of meteorological factors on the propagation of COVID-19. The correlation between 10 meteorological factors and the dynamic progression of COVID-19 was evaluated, employing spatial analysis techniques (spatial autocorrelation analysis, trend surface analysis, etc.) to describe the spatial and temporal characteristics of the epidemic. Leveraging the original ConvLSTM, an artificial neural network layer is introduced to learn how meteorological factors impact the infection spread, providing a 5-day forecast at a 0.01° × 0.01° pixel resolution. Simulation results using real dataset from the 3.15 outbreak in Shanghai demonstrate the efficacy of Meteor-ConvLSTM, with reduced RMSE of 0.110 and increased R 2 of 0.125 (original ConvLSTM: RMSE = 0.702, R 2 = 0.567; Meteor-ConvLSTM: RMSE = 0.592, R 2 = 0.692), showcasing its utility for investigating the epidemiological characteristics, transmission dynamics, and epidemic development.

Clinical feasibility of laparoscopic left lateral segment liver resection with magnetic anchor technique: The first clinical study from China.

BACKGROUND: Magnetic anchor technique (MAT) has been applied in laparoscopic cholecystectomy and laparoscopic appendectomy, but has not been reported in laparoscopic partial hepatectomy. AIM: To evaluate the feasibility of the MAT in laparoscopic left lateral segment liver resection. METHODS: Retrospective analysis was conducted on the clinical data of eight patients who underwent laparoscopic left lateral segment liver resection assisted by MAT in our department from July 2020 to November 2021. The Y-Z magnetic anchor devices (Y-Z MADs) was independently designed and developed by the author of this paper, which consists of the anchor magnet and magnetic grasping apparatus. Surgical time, intraoperative blood loss, intraoperative accidents, operator experience, postoperative incision pain score, postoperative complications, and other indicators were evaluated and analyzed. RESULTS: All eight patients underwent a MAT-assisted laparoscopic left lateral segment liver resection, including three patients undertaking conventional 5-port and five patients having a transumbilical single-port operation. The mean operation time was 138 ± 34.32 min (range 95-185 min) and the mean intraoperative blood loss was 123 ± 88.60 mL (range 20-300 mL). No adverse events occurred during the operation. The Y-Z MADs showed good workability and maneuverability in both tissue and organ exposure. In particular, the operators did not experience either a "chopstick" or "sword-fight" effect in the single-port laparoscopic operation. CONCLUSION: The results show that the MAT is safe and feasible for laparoscopic left lateral segment liver resection, especially, exhibits its unique abettance for transumbilical single-port laparoscopic left lateral segment liver resection.

EZH2/G9a interact to mediate drug resistance in non-small-cell lung cancer by regulating the SMAD4/ERK/c-Myc signaling axis.

Drug resistance is the leading problem in non-small-cell lung cancer (NSCLC) therapy. The contribution of histone methylation in mediating malignant phenotypes of NSCLC is well known. However, the role of histone methylation in NSCLC drug-resistance mechanisms remains unclear. Here, our data show that EZH2 and G9a, two histone methyltransferases, are involved in the drug resistance of NSCLC. Gene manipulation results indicate that the combination of EZH2 and G9a promotes tumor growth and mediates drug resistance in a complementary manner. Importantly, clinical study demonstrates that co-expression of both enzymes predicts a poor outcome in patients with NSCLC. Mechanistically, G9a and EZH2 interact and promote the silencing of the tumor-suppressor gene SMAD4, activating the ERK/c-Myc signaling pathway. Finally, SU08, a compound targeting both EZH2 and G9a, is demonstrated to sensitize resistant cells to therapeutic drugs by regulating the SMAD4/ERK/c-Myc signaling axis. These findings uncover the resistance mechanism and a strategy for reversing NSCLC drug resistance.

An Enzyme-Cleavable Solubilizing-Tag Facilitates the Chemical Synthesis of Mirror-Image Proteins.

Mirror-image proteins (D-proteins) are useful in biomedical research for purposes such as mirror-image screening for D-peptide drug discovery, but the chemical synthesis of many D-proteins is often low yielding due to the poor solubility or aggregation of their constituent peptide segments. Here, we report a Lys-C protease-cleavable solubilizing tag and its use to synthesize difficult-to-obtain D-proteins. Our tag is easily installed onto multiple amino acids such as DLys, DSer, DThr, and/or the N-terminal amino acid of hydrophobic D-peptides, is impervious to various reaction conditions, such as peptide synthesis, ligation, desulfurization, and transition metal-mediated deprotection, and yet can be completely removed by Lys-C protease under denaturing conditions to give the desired D-protein. The efficacy and practicality of the new method were exemplified in the synthesis of two challenging D-proteins: D-enantiomers of programmed cell death protein 1 IgV domain and SARS-CoV-2 envelope protein, in high yield. This work demonstrates that the enzymatic cleavage of solubilizing tags under denaturing conditions is feasible, thus paving the way for the production of more D-proteins.

L-Glycosidase-Cleavable Natural Glycans Facilitate the Chemical Synthesis of Correctly Folded Disulfide-Bonded D-Proteins.

D-peptide ligands can be screened for therapeutic potency and enzymatic stability using synthetic mirror-image proteins (D-proteins), but efficient acquisition of these D-proteins can be hampered by the need to accomplish their in vitro folding, which often requires the formation of correctly linked disulfide bonds. Here, we report the finding that temporary installation of natural O-linked-ß-N-acetyl-D-glucosamine (O-GlcNAc) groups onto selected D-serine or D-threonine residues of the synthetic disulfide-bonded D-proteins can facilitate their folding in vitro, and that the natural glycosyl groups can be completely removed from the folded D-proteins to afford the desired chirally inverted D-protein targets using naturally occurring O-GlcNAcase. This approach enabled the efficient chemical syntheses of several important but difficult-to-fold D-proteins incorporating disulfide bonds including the mirror-image tumor necrosis factor alpha (D-TNFα) homotrimer and the mirror-image receptor-binding domain of the Omicron spike protein (D-RBD). Our work establishes the use of O-GlcNAc to facilitate D-protein synthesis and folding and proves that D-proteins bearing O-GlcNAc can be good substrates for naturally occurring O-GlcNAcase.

SpyDirect: A Novel Biofunctionalization Method for High Stability and Longevity of Electronic Biosensors.

Electronic immunosensors are indispensable tools for diagnostics, particularly in scenarios demanding immediate results. Conventionally, these sensors rely on the chemical immobilization of antibodies onto electrodes. However, globular proteins tend to adsorb and unfold on these surfaces. Therefore, self-assembled monolayers (SAMs) of thiolated alkyl molecules are commonly used for indirect gold-antibody coupling. Here, a limitation associated with SAMs is revealed, wherein they curtail the longevity of protein sensors, particularly when integrated into the state-of-the-art transducer of organic bioelectronics-the organic electrochemical transistor. The SpyDirect method is introduced, generating an ultrahigh-density array of oriented nanobody receptors stably linked to the gold electrode without any SAMs. It is accomplished by directly coupling cysteine-terminated and orientation-optimized spyTag peptides, onto which nanobody-spyCatcher fusion proteins are autocatalytically attached, yielding a dense and uniform biorecognition layer. The structure-guided design optimizes the conformation and packing of flexibly tethered nanobodies. This biolayer enhances shelf-life and reduces background noise in various complex media. SpyDirect functionalization is faster and easier than SAM-based methods and does not necessitate organic solvents, rendering the sensors eco-friendly, accessible, and amenable to scalability. SpyDirect represents a broadly applicable biofunctionalization method for enhancing the cost-effectiveness, sustainability, and longevity of electronic biosensors, all without compromising sensitivity.

The study on the effect of mercury pollution on soil microorganisms around mercury mining area.

In order to further explore the effects of soil mercury pollution on soil microbial diversity and community structure, soil samples were randomly collected from 2 m, 20 m, 30 m, 500 m and 650 m periphery of Wanshan mining area, as 5 different treatments. Each treatment had 4 replicates. Soil microbial DNA was extracted from 20 soil samples, and then high-throughput sequencing technology was used to analyse the structure and distribution of bacterial and fungal communities. The results showed that the number of bacterial and fungal communities in T0-T30 treatments was significantly larger than that in T500-T650 treatments at order, family and genus level. Whatever, the number of uniquely distributed bacterial and fungal communities among 4 replicates soil samples was quite different at order, family and genus level. The results of the effect on the microbial community structure showed that there were both the same dominant bacterial and fungal communities, and the different dominant bacterial and fungal communities at any classification level, moreover, the number of same dominant bacterial and fungal communities was larger than that of different dominant bacterial and fungal communities. The results of relationship between soil environment factors and bacterial and fungal community structure showed that distance (Hg2+), EC and pH had a high correlation with community structure, especially the distance factor, that is, the content of mercury in soil had the highest effects on community structure. The internal heterogeneity of soil caused significant differences in bacterial and fungal community structure, and the emergence of dominant bacterial and fungal communities was a manifestation of better adaptability to long-term mercury stress and other stresses in soil, which will provide a scientific reference for further exploring the mechanism of mercury enrichment between microorganisms and plants.

Identifying multi-target drugs for prostate cancer using machine learning-assisted transcriptomic analysis.

Prostate cancer is a leading cause of cancer death in men, and the development of effective treatments is of great importance. This study explored to identify the candidate drugs for prostate cancer by transcriptomic data and CMap database analysis. After integrating the results of omics analysis, bisoprolol is confirmed as a promising drug. Moreover, cell experiment reveals its potential inhibitory effect on the proliferation of prostate cancer cells. Importantly, machine learning methods are employed to predict the targets of bisoprolol, and the dual-target ADRB3 and hERG are explored by dynamic simulation. The findings of this study demonstrate the potential of bisoprolol as a multi-target drug for prostate cancer treatment and the feasibility of using beta-adrenergic receptor inhibitors in prostate cancer treatment. In addition, the proposed research approach is promising for discovering potential drugs for cancer treatment by leveraging the concept of drug side effects leading to anticancer effects. Further research is necessary to investigate the pharmacological action, potential toxicity, and underlying mechanisms of bisoprolol in treating prostate cancer with ADRB3.Communicated by Ramaswamy H. Sarma.

Primary animal experiment to test the feasibility of a novel Y-Z magnetic hepatic portal blocking band.

BACKGROUND: Hepatic portal blood flow occlusion is a common technique for reducing hepatic hemorrhage during hepatectomy. We designed a novel Y-Z magnetic hepatic portal blocking band (Y-Z MHPBB) based on the principle of magnetic compression technique. AIM: To introduce the Y-Z MHPBB device and verify the feasibility of this device for hepatic portal blood flow occlusion in dogs. METHODS: Ten beagles were randomly divided into the experimental group and control group. The operation time, intraoperative blood loss, the number of portal blood flow occlusions, the total time spent on adjusting the blocking band, and the average time spent on adjusting the blocking band were recorded. The surgeons evaluated the feasibility and flexibility of the two portal occlusion devices. RESULTS: Laparoscopic hepatectomy was successfully performed in both the experimental group and control group. There was no statistical difference between the two groups in the operation time, intraoperative blood loss, and the number of hepatic portal blood flow occlusions. With respect to the total time spent on adjusting the blocking band and the average time spent on adjusting the blocking band, the experimental group showed significantly better outcomes than the control group, with a statistical difference (P < 0.05). The operators found that the Y-Z MHPBB was superior to the modified T-tube in terms of operational flexibility. CONCLUSION: The Y-Z MHPBB seems to be an ingenious design, accurate blood flow occlusion effect, and good flexibility; and it can be used for hepatic portal blood flow occlusion during laparoscopic hepatectomy.

The pattern of collagen production may contribute to the gluteal muscle contracture pathogenic process.

INTRODUCTION: Arthroscopic release is now the gold standard globally for gluteal muscle contracture (GMC) treatment. However, some patients fail to improve after the first operation and are forced to undergo a second operation. This study explores the essential role collagen fibers may play in muscle contracture in GMC. METHODS: From February 2010 to May 2018, 1041 hips of 543 GMC patients underwent arthroscopic release. Among them, 498 (91.7%) patients had bilateral GMC and were admitted to the retrospective cohort study. Pathological testing and type III collagen testing were used in contracture tissue studies. Single-cell RNA-sequencing analysis was applied to explore the role of fibroblasts in muscle repair. RESULTS: Compared with GMC II patients, GMC III patients displayed higher clinical symptoms (P < 0.05). Six weeks after the surgery, the patients in GMC II had a lower prominent hip snap rate, higher JOA score, and better hip range of motion (P < 0.05). Compared with normal muscle tissue, contracture-affected tissue tended to have more type III collagen and form shorter fibers. Recurrent GMC patients seemed to have a higher type III collagen ratio (P < 0.05). In contrast to normally repairable muscle defects, fibroblasts in non-repairable defects were shown to downregulate collagen-related pathways at the early and late stages of tissue repair. DISCUSSION: This study describes the arthroscopic release of GMC. Study findings include the suggestion that the collagen secretion function of fibroblasts and collagen pattern might influence the muscle repair ability and be further involved in the GMC pathogenic process.

Magnetic anchor technique assisted laparoscopic cholecystectomy in swine.

Magnetic anchor device based on the principle of magnet heteropolar attraction can assist laparoscopic surgery and reduce abdominal wall trauma. This study explored the feasibility of use of our self-designed magnetic anchor device for reduced-port laparoscopic cholecystectomy (LC) through animal experiments. Twelve experimental pigs (15-20 kg) were randomly divided into study group (magnetic anchor technique assisted 2-port LC, n = 6) and control group (conventional 3-port LC, n = 6). Operative time, intraoperative blood loss, and postoperative complications were compared between the two groups. LC was successfully performed in all 12 pigs. There was no significant between-group difference with respect to operative time (study group: 35.83 ± 5.12 min; control group: 34.50 ± 5.13 min, P = 0.662) or intraoperative blood loss (< 50 mL per animal in both groups). In the experimental group, there was no malfunction of the magnetic anchoring device, the use process was smooth, and the tissue traction and surgical field exposure were satisfactory. There were no perioperative complications such as bile duct injury, bile leakage, or bleeding in both groups. We demonstrated the feasibility of use of the self-designed magnetic anchor device in reduced-port LC. The device has important clinical application value.

Clinical application of magnetic anchor technique in laparoscopic cholecystectomy: the first retrospective study in China.

Background and objectives: Magnetic anchor technique (MAT) is frequently used in laparoscopic cholecystectomy. However, there are few reports on its clinical application in China. In this study, we retrospectively analyzed the clinical application of MAT in laparoscopic cholecystectomy in China. Materials and methods: 25 patients (4 males, 21 females) who underwent laparoscopic cholecystectomy assisted by MAT at the First Affiliated Hospital of Xi'an Jiaotong University were enrolled from November 2020 to March 2021. Their records were retrospectively analyzed. The magnetic anchor device was independently designed and developed by the authors and consisted of the anchor magnet and magnetic grasping apparatus. Surgical time, intraoperative blood loss, intraoperative accidents, operator experience, postoperative incision pain score, postoperative complications, and other indicators were evaluated and analyzed. Results: All patients successfully underwent laparoscopic cholecystectomy, including 3 cases of MAT-assisted transumbilical single-port LC, 16 cases of MAT-assisted 2-port LC and 6 cases of conventional 3-port LC. The median operation time was 50 min (range 30-95 min); intraoperative bleeding was less than 30 ml. The median score of surgical incision on day 1 and 3 after the operation was 3 (range 1-4) and 1 (range 1-3), respectively. All patients had no intraoperative bile duct injury, vascular injury, postoperative bleeding, bile leakage, biliary stricture and other complications. No adverse events (such as injury to adjacent organs or failure of the magnetic anchor device) occurred either during or after the operation. Conclusions: The MAT-assisted laparoscopic cholecystectomy appears to be safe, feasible and effective and exhibits unique assistance in transumbilical single-port laparoscopic cholecystectomy.

The Acyl-CoA Specificity of Human Lysine Acetyltransferase KAT2A.

Protein post-translational modifications serve to regulate a broad range of cellular functions including signal transduction, transcription, and metabolism. Protein lysine residues undergo many post-translational acylations and are regulated by a range of enzymes, such as histone acetyl transferases (HATs) and histone deacetylases (HDACs). KAT2A, well characterized as a lysine acetyltransferase for both histone and nonhistone substrates, has been reported to tolerate additional acyl-CoA substrates, such as succinyl-CoA, and shows nonacetyl transferase activity in specific biological contexts. In this work, we investigate the acyl-CoA substrate preference of KAT2A and attempt to determine whether and to what extent additional acyl-CoA substrates may be utilized by KAT2A in a cellular context. We show that while KAT2A can bind and utilize malonyl-CoA, its activity with succinyl-CoA or glutaryl-CoA is very weak, and acetylation is still the most efficient activity for KAT2A in vitro and in cells.

A novel magnetic compression technique for cystostomy in rabbits.

Magnetic compression technique (MCT) is a popular new anastomosis method. In this paper, we aimed to explore the feasibility of use of MCT for performing cystotomy in rabbits. The parent magnets and daughter magnets for rabbit cystostomy were designed and manufactured according to the anatomical characteristics of rabbit lower urinary tract. Twelve female New Zealand rabbits were used as animal models. After anesthesia, a daughter magnet was inserted into the bladder through the urethra, and the parent magnet was placed on the body surface projection of the bladder over the abdominal wall. The two magnets automatically attract each other. Postoperatively, the state of magnets was monitored daily, and the time when the magnets fell off was recorded. Cystostomy with MCT was successfully performed in all twelve rabbits. The mean operation time was 4.46 ± 0.75 min. The magnets fell off from the abdominal wall after a mean duration of 10.08 ± 1.62 days, resulting in the formation of bladder fistula. Macroscopic and microscopic examination showed that the fistula was well formed and unobstructed. The junction between bladder and abdominal wall was tight and smooth. We provide preliminary experimental evidence of the safety and feasibility of cystostomy based on MCT.

Tunable Transmissive Terahertz Linear Polarizer for Arbitrary Linear Incidence Based on Low-Dimensional Metamaterials.

In this work, we propose a structure consisting of three metamaterial layers and a metallic grating layer to rotate the polarization of arbitrary linearly polarized incidence to the y-direction with high transmissivity by electrically tuning these metamaterials. The transfer matrix method together with a harmonic oscillator model is adopted to theoretically study the proposed structure. Numerical simulation based on the finite difference time-domain method is performed assuming that the metamaterial layers are constituted by graphene ribbon arrays. The calculation and simulation results show that the Drude absorption is responsible for the polarization rotation. Fermi level and scattering rate of graphene are important for the transmissivity. For a polarization rotation of around 90°, the thickness of either the upper or lower dielectric separations influences the transmission window. For a polarization rotation of around 45° and 135°, the lower dielectric separations decide the frequency of the transmission window, while the upper dielectric separations just slightly influence the transmissivity.

Anatomical knee variables result in worse outcomes of lateral meniscal allograft transplantation with discoid lateral menisci than with nondiscoid lateral menisci.

PURPOSE: To compare the clinical results of meniscal allograft transplantation (MAT) between patients with discoid lateral meniscus (DLM) and non-DLM (NDLM) and to analyse whether anatomical deformities cause worse clinical results in DLM patients. METHODS: Patients who underwent unilateral MAT from 2005 to 2017, including 115 patients with DLMs or NDLMs, were included in this study. Clinical outcomes [International Knee Documentation Committee (IKDC) scores, Lysholm scores, Tegner scores, and visual analogue scale (VAS) scores] and radiographic and MRI data were assessed. Clinical outcomes and anatomical knee variables were analysed by multivariate stepwise regression. RESULTS: After more than 2 years of follow-up, 9 patients were lost to follow-up, and 59 patients with DLM and 47 patients with NDLM were included. The mean postoperative results were significantly better than the preoperative data (P < 0.05) in both the DLM and NDLM groups. In addition, postoperative IKDC, Lysholm, and VAS scores but not Tegner scores were better in the NDLM group than in the DLM group. Several anatomical knee variables differed significantly between the NDLM and DLM groups and were associated with MAT outcomes. The condylar prominence ratio of the lateral and medial femoral condyles adjacent to the intercondylar notch and squaring of the lateral femoral condyle (the distance of the straight articular condylar surface) were independent factors significantly correlated with the Lysholm scores for MAT at last follow-up. CONCLUSION: MAT improved knee function in both patients with DLM and patients with NDLM, but patients NDLM had better clinical outcomes than patients with DLM. The condylar prominence ratio and squaring of the lateral femoral condyle may underlie this result. LEVEL OF EVIDENCE: III.

Anomalous insertion of the anterior horn of the medial meniscus combined with anterior horn hypertrophy and a synovial cyst: case report and literature review.

OBJECTIVE: To gain a greater understanding of anomalous insertions of the anterior horn of the medial meniscus through evaluation of a rare case and a review of the existing literature on medial meniscus malformations. METHODS: This report describes a 26-year-old man with an anomalous insertion of the anterior horn of the medial meniscus combined with symptomatic hypertrophy of the anterior horn and a synovial cyst. We also conducted a review of the existing literature on medial meniscus malformations using five major scholarly literature databases and search engines. RESULTS: The literature review revealed that the incidence of anomalous insertions of the anterior horn of the medial meniscus is 0.5% to 2.8%. Not all patients undergo surgical excision; some are only symptomatically treated. In our patient, the arthroscopic view was consistent with the imaging characteristics. No special operation was performed to treat the anomalous insertion. At the 18-month follow-up, the patient had no symptom recurrence and had returned to practicing sports. CONCLUSION: The pain during hyperextension in our patient was caused by a cyst and anterior horn hypertrophy. If the symptoms in such cases are not caused by the anomalous insertion, no special treatment is needed.

Arsenic behavior across soil-water interfaces in paddy soils: Coupling, decoupling and speciation.

The sharp redox gradient at soil-water interfaces (SWI) plays a key role in controlling arsenic (As) translocation and transformation in paddy soils. When Eh drops, As is released to porewater from solid iron (Fe) and manganese (Mn) minerals and reduced to arsenite. However, the coupling or decoupling processes operating within the redox gradient at the SWI in flooded paddy soils remain poorly constrained due to the lack of direct evidence. In this paper, we reported the mm-scale mapping of Fe, As and other associated elements across the redox gradient in the SWI of five different paddy soils. The results showed a strong positive linear relationship between dissolved Fe, Mn, As, and phosphorus (P) in 4 out of the 5 paddy soils, indicating the general coupling of these elements. However, decoupling of Fe, Mn and As was observed in one of the paddy soils. In this soil, distinct releasing profiles of Mn, As and Fe were observed, and the releasing order followed the redox ladder. Further investigation of As species showed the ratio of arsenite to total As dropped from 100% to 75.5% and then kept stable along depth of the soil profile, which indicates a dynamic equilibrium between arsenite oxidization and arsenate reduction. This study provides direct evidence of multi-elements' interaction along redox gradient of SWI in paddy soils.

Terahertz Broadband Polarization Conversion for Transmitted Waves Based on Graphene Plasmon Resonances.

We applied the harmonic oscillator model combined with the transfer matrix method to study the polarization conversion for transmitted waves in metallic grating/plasmon-excitation layer/metallic grating structure in the terahertz (THz) region. By comparing the calculated spectra and the simulated (by the finite-difference-time-domain method) ones, we found that they correspond well with each other. Both methods show that the Drude background absorption and the excited plasmon resonances are responsible for polarization conversion. The transmission is close to 0 when the distance between the top/bottom metallic gratings and gated graphene is an integer multiple of half the wavelength of the incident wave (in the dielectrics), at which points the plasmon resonances are greatly suppressed by the destructive interference between the backward/forward electromagnetic waves and that reflected by the top/bottom metallic gratings. Away from these points, the transmission can be higher than 80%. The electron density and the excitation efficiency of the plasmon-excitation layer were found to be important for the bandwidth of the polarization conversion window, while the scattering rate was found to influence mainly the polarization conversion rate. Multi-broadband polarization conversion is realized by exciting plasmon modes between the 0 transmission points in the THz region.