Dynamic Microcirculation Characteristics of Plantar Skin Under Metatarsal Head of Human Foot in Response to Life-Like Pressure Stimulus.

OBJECTIVE: Diabetic foot ulcer (DFU) is a severe complication with high mortality. High plantar pressure and poor microcirculation are considered main causes of DFU. The specific aims were to provide a novel technique for real-time measurement of plantar skin blood flow (SBF) under walking-like pressure stimulus and delineate the first plantar metatarsal head dynamic microcirculation characteristics because of life-like loading conditions in healthy individuals. METHODS: Twenty young healthy participants (14 male and 6 female) were recruited. The baseline (i.e., unloaded) SBF of soft tissue under the first metatarsal head were measured using laser Doppler flowmetry (LDF). A custom-made machine was utilized to replicate daily walking pressure exertion for 5 min. The exerted plantar force was adjusted from 10 N (127.3 kPa) to 40 N (509.3 kPa) at an increase of 5 N (63.7 kPa). Real-time SBF was acquired using the LDF. After each pressure exertion, postload SBF was measured for comparative purposes. Statistical analysis was performed using the R software. RESULTS: All levels of immediate-load and postload SBF increased significantly compared with baseline values. As the exerted load increased, the postload and immediate-load SBF tended to increase until the exerted load reached 35 N (445.6 kPa). However, in immediate-load data, the increasing trend tended to level off as the exerted pressure increased from 15 N (191.0 kPa) to 25 N (318.3 kPa). For postload and immediate-load SBF, they both peaked at 35 N (445.6 kPa). However, when the exerted force exceeds 35 N (445.6 kPa), both the immediate-load and postload SBF values started to decrease. CONCLUSIONS: Our study offered a novel real-time plantar soft tissue microcirculation measurement technique under dynamic conditions. For the first metatarsal head of healthy people, 20 N (254.6 kPa)-plantar pressure has a fair microcirculation stimulus compared with higher pressure. There might be a pressure threshold at 35 N (445.6 kPa) for the first metatarsal head, and soft tissue microcirculation may decrease when local pressure exceeds it.

TBC1D5 reverses the capability of HIF-2α in tumor progression and lipid metabolism in clear cell renal cell carcinoma by regulating the autophagy.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is known for abnormal lipid metabolism and widespread activation of HIF-2α. Recently, the importance of autophagy in ccRCC has been focused, and it has potential connections with HIF-2α and lipid metabolism. However, the specific regulatory mechanism between HIF-2α, autophagy, and lipid metabolism in ccRCC is still unclear. METHODS: In this study, Bioinformatics Analysis and Sequencing of the whole transcriptome were used to screen our target. The expression of TBC1D5 in renal clear cell carcinoma was confirmed by database analysis, immunohistochemistry, PCR and Western blot. The effects of TBC1D5 on tumor cell growth, migration, invasion and lipid metabolism were examined by CCK8, Transwell and oil red staining, and the mechanism of TBC1D5 on autophagy was investigated by Western blot, fluorescence microscopy and electron microscopy. Chloroquine and rapamycin were used to verified the key role of autophagy in effects of TBC1D5 on tumor cell. The regulatory mechanism of TBC1D5 in renal clear cell carcinoma (RCC) was investigated by shhif-2α, shTBC1D5, mimic, inhibitor, ChIP and Luciferase experiments. The animal model of ccRCC was used to evaluate the biological function of TBC1D5 in vivo. RESULTS: In this study, TBC1D5 was found to be an important bridge between autophagy and HIF-2α. Specifically, TBC1D5 is significantly underexpressed in ccRCC, serving as a tumor suppressor which inhibits tumor progression and lipid accumulation, and is negatively regulated by HIF-2α. Further research has found that TBC1D5 regulates the autophagy pathway to reverse the biological function of HIF-2α in ccRCC. Mechanism studies have shown that HIF-2α regulates TBC1D5 through hsa-miR-7-5p in ccRCC, thereby affecting tumor progression and lipid metabolism through autophagy. CONCLUSIONS: Our research reveals a completely new pathway, HIF-2α/hsa-miR-7-5p/TBC1D5 pathway affects ccRCC progression and lipid metabolism by regulating autophagy.

Genomic basis of the distinct biosynthesis of ß-glucogallin, a biochemical marker for hydrolyzable tannin production, in three oak species.

Hydrolyzable tannins (HTs), predominant polyphenols in oaks, are widely used in grape wine aging, feed additives, and human healthcare. However, the limited availability of a high-quality reference genome of oaks greatly hampered the recognition of the mechanism of HT biosynthesis. Here, high-quality reference genomes of three Asian oak species (Quercus variabilis, Quercus aliena, and Quercus dentata) that have different HT contents were generated. Multi-omics studies were carried out to identify key genes regulating HT biosynthesis. In vitro enzyme activity assay was also conducted. Dual-luciferase and yeast one-hybrid assays were used to reveal the transcriptional regulation. Our results revealed that ß-glucogallin was a biochemical marker for HT production in the cupules of the three Asian oaks. UGT84A13 was confirmed as the key enzyme for ß-glucogallin biosynthesis. The differential expression of UGT84A13, rather than enzyme activity, was the main reason for different ß-glucogallin and HT accumulation. Notably, sequence variations in UGT84A13 promoters led to different trans-activating activities of WRKY32/59, explaining the different expression patterns of UGT84A13 among the three species. Our findings provide three high-quality new reference genomes for oak trees and give new insights into different transcriptional regulation for understanding ß-glucogallin and HT biosynthesis in closely related oak species.

Plant YABBY transcription factors: a review of gene expression, biological functions, and prospects.

Transcription factors often contain several different functional regions, including DNA-binding domains, and play an important regulatory role in plant growth, development, and the response to external stimuli. YABYY transcription factors are plant-specific and contain two special domains (N-terminal C2C2 zinc-finger and C-terminal helix-loop-helix domains) that are indispensable. Specifically, YABBY transcription factors play key roles in maintaining the polarity of the adaxial-abaxial axis of leaves, as well as in regulating: vegetative and reproductive growth, hormone response, stress resistance, and secondary metabolite synthesis in plants. Recently, the identification and functional verification of YABBY transcription factors in different plants has increased. On this basis, we summarize recent advances in the: identification, classification, expression patterns, and functions of the YABBY transcription factor family. The normal expression and function of YABBY transcription factors rely on a regulatory network that is established through the interaction of YABBY family members with other genes. We discuss the interaction network of YABBY transcription factors during leaf polarity establishment and floral organ development. This article provides a reference for research on YABBY function, plant genetic improvement, and molecular breeding.

Self-adaptive and efficient propulsion of Ray sperms at different viscosities enabled by heterogeneous dual helixes.

We disclose a peculiar rotational propulsion mechanism of Ray sperms enabled by its unusual heterogeneous dual helixes with a rigid spiral head and a soft tail, named Heterogeneous Dual Helixes (HDH) model for short. Different from the conventional beating propulsion of sperm, the propulsion of Ray sperms is from both the rotational motion of the soft helical tail and the rigid spiral head. Such heterogeneous dual helical propulsion style provides the Ray sperm with high adaptability in viscous solutions along with advantages in linearity, straightness, and bidirectional motion. This HDH model is further corroborated by a miniature swimming robot actuated via a rigid spiral head and a soft tail, which demonstrates similar superiorities over conventional ones in terms of adaptability and efficiency under the same power input. Such findings expand our knowledge on microorganisms' motion, motivate further studies on natural fertilization, and inspire engineering designs.

Novel decision tree models predict the overall survival of patients with submandibular gland cancer.

BACKGROUND: While the accurate prediction of the overall survival (OS) in patients with submandibular gland cancer (SGC) is paramount for informed therapeutic planning, the development of reliable survival prediction models has been hindered by the rarity of SGC cases. The purpose of this study is to identify key prognostic factors for OS in SGC patients using a large database and construct decision tree models to aid the prediction of survival probabilities in 12, 24, 60 and 120 months. MATERIALS AND METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology and End Result (SEER) program. Demographic and peri-operative predictor variables were identified. The outcome variables overall survival at 12-, 24-, 60, and 120 months. The C5.0 algorithm was utilized to establish the dichotomous decision tree models, with the depth of tree limited within 4 layers. To evaluate the performances of the novel models, the receiver operator characteristic (ROC) curves were generated, and the metrics such as accuracy rate, and area under ROC curve (AUC) were calculated. RESULTS: A total of 1,705, 1,666, 1,543, and 1,413 SGC patients with a follow up of 12, 24, 60 and 120 months and exact survival status were identified from the SEER database. Predictor variables of age, sex, surgery, radiation, chemotherapy, tumor histology, summary stage, metastasis to distant lymph node, and marital status exerted substantial influence on overall survival. Decision tree models were then developed, incorporating these vital prognostic indicators. Favorable consistency was presented between the predicted and actual survival statuses. For the training dataset, the accuracy rates for the 12-, 24-, 60- and 120-month survival models were 0.866, 0.767, 0.737 and 0.797. Correspondingly, the AUC values were 0.841, 0.756, 0.725, and 0.774 for the same time points. CONCLUSIONS: Based on the most important predictor variables identified using the large, SEER database, decision tree models were established that predict OS of SGC patients. The models offer a more exhaustive evaluation of mortality risk and may lead to more personalized treatment strategies.

Combined Remediation Effects of Sewage Sludge and Phosphate Fertilizer on Pb-Polluted Soil from a Pb-Acid Battery Plant.

Pb soil pollution poses a serious health risk to both the environment and humans. Immobilization is the most common strategy for remediation of heavy metal polluted soil. In this study, municipal sewage sludge was used as an amendment for rehabilitation of Pb-contaminated soils, for agricultural use, near a lead-acid battery factory. The passivation effect was further improved by the addition of phosphate fertilizer. It was found that the leachable Pb content in soils was decreased from 49.6 mg kg-1 to 16.1-36.6 mg kg-1 after remediation of sludge for 45 d at applied dosage of municipal sewage sludge of 4-16 wt%, and further decreased to 14.3-34.3 mg kg-1 upon extension of the remediation period to 180 d. The addition of phosphate fertilizer greatly enhanced the Pb immobilization, with leachable Pb content decreased to 2.0-23.6 mg kg-1 with increasing dosage of phosphate fertilizer in range of 0.8-16 wt% after 180 d remediation. Plant assays showed that the bioavailability of Pb was significantly reduced by the soil remediation, with the content of absorbed Pb in mung bean roots decreased by as much as 87.0%. The decrease in mobility and biotoxicity of the soil Pb is mainly attributed to the speciation transformation of carbonate, Fe-Mn oxides and organic matter bound Pb to residue Pb under the synergism of reduction effect of sludge and acid dissolution and precipitation effect of phosphate fertilizer. This study suggests a new method for remediation of Pb-contaminated soil and utilization of municipal sewage sludge resources.

Genome-wide identification and molecular characterization of the AP2/ERF superfamily members in sand pear (Pyrus pyrifolia).

BACKGROUND: 'Whangkeumbae' (Pyrus pyrifolia) is a typical climacteric fruit variety of sand pear with excellent taste. However, the rapid postharvest ethylene production limits the shelf life of 'Whangkeumbae' fruit. AP2/ERF superfamily is a large family of transcription factors involved in plant growth and development, including fruit ripening and senescence through the ethylene signaling pathway. The numbers and functions of AP2/ERF superfamily members in sand pear remain largely unknown. RESULTS: In this study, a total of 234 AP2/ERF family members were identified through the transcriptome of Pyrus pyrifolia 'Whangkeumbae' (17 genes) and Pyrus pyrifolia genome (223 genes) analyses. Six genes (Accession: EVM0023062.1, EVM0034833.1, EVM0027049.1, EVM0034047.1, EVM0028755.1, EVM0015862.1) identified via genome analysis shared 100% identity with PpERF14-L, PpERF5-L, PpERF3a, PpERF3, PpERF017 and PpERF098, respectively, which were identified from transcriptome sequencing. Further, the AP2/ERF superfamily members were divided into AP2, ERF, and RAV subfamilies, each comprising 38, 188, and 8 members, respectively. Tissue-specific expression analysis showed that PpERF061, PpERF113, PpERF51L-B, PpERF5-L, and PpERF017 were predominantly expressed in fruits than in other tissues. Additionally, PpERF5-L and PpERF017 showed higher expressions at the early stage of fruit development. While, PpERF51B-L exhibited higher expression during the fruit ripening stage. Besides, PpERF061 and PpERF113 had pronounced expressions during fruit senescence. CONCLUSION: These results indicate that PpERF061, PpERF113, PpERF51L-B, PpERF5-L, and PpERF017 could play crucial roles in sand pear fruit development, ripening, and senescence. Overall, this study provides valuable information for further functional analysis of the AP2/ERF genes during fruit ripening and senescence in sand pear.

Enhancing Resistance to Chloride Corrosion by Controlling the Morphologies of PtNi Electrocatalysts for Alkaline Seawater Hydrogen Evolution.

A solvothermal method to prepare PtNi alloys that have differing morphologies is described. By adjusting the feed ratio of Pt and Ni precursors in this process, PtNi alloys with different compositions (Pt : Ni atomic ratio from 1 : 3 to 3 : 1) and morphologies (evolution from nanobranches to nanoparticles) are generated. The prepared Pt48 Ni52 alloy, which has a composite morphology comprised of nanobranches and nanoparticles, exhibits superior activity and durability towards the hydrogen evolution reaction (HER) in seawater compared to those of commercial Pt/C catalyst and other PtNi alloys that have different compositions and morphologies. The excellent seawater HER performance of Pt48 Ni52 is ascribed to its nanobranch/nanoparticle morphology that optimally facilitates electron accumulation on Pt, which enhances resistance to chloride corrosion in seawater.

Association between polymorphisms of the GSDMB gene and allergic rhinitis risk in the Chinese population: a case-control study.

BACKGROUND: Allergic rhinitis (AR) is a great risk factor for developing asthma, and its pathogenesis is affected by various factors, such as gene and environment. GSDMB is related to allergic diseases. Our purpose is to explore the correlation of single nucleotide polymorphisms (SNPs) in GSDMB and AR risk in the Chinese population. METHODS: We performed a case-control study including 1005 cases and 1004 controls. Rs2305479, rs4795400, and rs12450091 in GSDMB were geneotyped using Agena MassARRAY. The relationships between GSDMB SNPs and AR risk were assessed by logistic regression analysis in PLINK1.9. RESULTS: Our study showed that rs4795400 was a protective factor for AR in overall (TT vs. CC: OR = 0.66, p = 0.009; TT vs. CC/TC: OR = 0.67, p = 0.008; additive: OR = 0.87, p = 0.042 males, people with BMI ≤ 24, and living in wind-blown sand area. Rs2305479 was associated with a reduced AR risk in males (TT vs. CC: OR = 0.47, p = 0.014; TT vs. CC/TC: OR = 0.43, p = 0.004). However, rs12450091 was a risk factor for AR in people living in the loess hilly region (CC: OR = 4.75, p = 0.047). The levels of EO and EO_per in the case group were significantly higher than those in the control group (p < 0.05). CONCLUSION: This study indicated that GSDMB polymorphisms (rs4795400, rs2305479, and rs12450091) were associated with AR susceptibility. Further studies are required to confirm our findings and to clarify the functional relationship.

Robotic versus Laparoscopic Total Mesorectal Excision Surgery in Rectal Cancer: Analysis of Medium-Term Oncological Outcomes.

Background. Robotic systems can overcome some limitations of laparoscopic total mesorectal excision (L-TME), thus improving the quality of the surgery. So far, many studies have reported the technical feasibility and short-term oncological results of robotic total mesorectal excision (R-TME) in treating rectal cancer (RC); however, only a few evaluated the survival and long-term oncological outcomes. The following study compared the medium-term oncological data, 3-year overall survival (OS), and disease-free survival (DFS) of L-TME and R-TME in patients with rectal cancer. Methods. In this retrospective study, records of patients (patients with stage I-III rectal cancer) who underwent surgery (127 cases of L-TME and 148 cases of R-TME) at the Gansu Provincial Hospital between June 2016 and March 2018 were included in the analysis. Kaplan-Meier analysis evaluated the 3-year OS and DFS for all patients treated with curative intent. Results. The conversion rate was significantly higher, and the postoperative hospital stay was significantly longer in the L-TME group than in the R-TME group (all P<.05). Major complications were significantly lower in the robotic group (P<.05). The 3-year DFS rate (for all stages) was 74.8% for L-TME and 85.8% for R-TME (P = .021). For disease stage III, the 3-year DFS and OS were significantly higher in the R-TME group (P<.05). Conclusion. R-TME can achieve better oncological outcomes and is more beneficial for RC patients compared with L-TME, especially for those with stage III rectal cancers. Nevertheless, further randomized controlled trials and a longer follow-up period are needed to confirm these findings.

Progress of Artificial Intelligence in Drug Synthesis and Prospect of Its Application in Nitrification of Energetic Materials.

Artificial intelligence technology shows the advantages of improving efficiency, reducing costs, shortening time, reducing the number of staff on site and achieving precise operations, making impressive research progress in the fields of drug discovery and development, but there are few reports on application in energetic materials. This paper addresses the high safety risks in the current nitrification process of energetic materials, comprehensively analyses and summarizes the main safety risks and their control elements in the nitrification process, proposes possibilities and suggestions for using artificial intelligence technology to enhance the "essential safety" of the nitrification process in energetic materials, reviews the research progress of artificial intelligence in the field of drug synthesis, looks forward to the application prospects of artificial intelligence technology in the nitrification of energetic materials and provides support and guidance for the safe processing of nitrification in the propellants and explosives industry.

High-efficiency electrochemical removal of Cd(II) from wastewater using birnessite-biochar composites: Performance and mechanism.

Birnessite has been widely used for electrochemical removal of heavy metals due to its high pseudocapacitance. Incorporation of carbon-based materials into birnessite can enhance its conductivity and stability, and synergistically improve the electrochemical adsorption capacity due to the double-layer capacitor reaction derived from carbon-based materials. In this study, biochar was successfully incorporated with birnessite at various ratios to synthesize composites (BC-Mn) for effective electrochemical removal of cadmium (Cd(II)) from water. The effects of cell voltage, initial pH, and recycling performance of BC-Mn were evaluated. As a result, the electrosorption capacity of BC-Mn for Cd(II) exhibited gradual increases with increasing birnessite content and reached equilibrium at a Mn content of 20% (BC-Mn20). The Cd(II) adsorption capacity of BC-Mn20 rose at higher cell voltage, and reached the maximum at 1.2 V. At pH 3.0-6.0, the electrosorption capacity initially rose until pH 5.0 and then approached equilibrium with a further increase in pH value. The Cd(II) electrochemical adsorption capacity of BC-Mn20 in the solution could reach 104.5 mg g-1 at pH 5.0 for 8 h at 1.2 V. Moreover, BC-Mn20 exhibited excellent reusability with a stability of 95.4% (99.7 mg g-1) after five cycles of reuse. Due to its superior heavy metal adsorption capacity and reusability, BC-Mn20 may have a promising prospect in the remediation of heavy metal polluted water.

Orexin-A Intensifies Mouse Pupillary Light Response by Modulating Intrinsically Photosensitive Retinal Ganglion Cells.

We show for the first time that the neuropeptide orexin modulates pupillary light response, a non-image-forming visual function, in mice of either sex. Intravitreal injection of the orexin receptor (OXR) antagonist TCS1102 and orexin-A reduced and enhanced pupillary constriction in response to light, respectively. Orexin-A activated OX1Rs on M2-type intrinsically photosensitive retinal ganglion cells (M2 cells), and caused membrane depolarization of these cells by modulating inward rectifier potassium channels and nonselective cation channels, thus resulting in an increase in intrinsic excitability. The increased intrinsic excitability could account for the orexin-A-evoked increase in spontaneous discharges and light-induced spiking rates of M2 cells, leading to an intensification of pupillary constriction. Orexin-A did not alter the light response of M1 cells, which could be because of no or weak expression of OX1Rs on them, as revealed by RNAscope in situ hybridization. In sum, orexin-A is likely to decrease the pupil size of mice by influencing M2 cells, thereby improving visual performance in awake mice via enhancing the focal depth of the eye's refractive system.SIGNIFICANCE STATEMENT This study reveals the role of the neuropeptide orexin in mouse pupillary light response, a non-image-forming visual function. Intravitreal orexin-A administration intensifies light-induced pupillary constriction via increasing the excitability of M2 intrinsically photosensitive retinal ganglion cells by activating the orexin receptor subtype OX1R. Modulation of inward rectifier potassium channels and nonselective cation channels were both involved in the ionic mechanisms underlying such intensification. Orexin could improve visual performance in awake mice by reducing the pupil size and thereby enhancing the focal depth of the eye's refractive system.

SO2/NO2 Separation Driven by NO2 Dimerization on SSZ-13 Zeolite Membrane.

The molecular state is crucial for precise gas separation using a zeolite membrane, yet the state control remains a big challenge. Herein, we report a NO2 dimerization facilitated high performance SO2/NO2 separation on a SSZ-13 zeolite membrane. The NO2 dimerization is triggered by temperature and pressure to form N2O4 with big molecular size, and N2O4 diffusion into the zeolite pore is inhibited on the basis of size exclusion, leading to high separation selectivity. Consequently, SO2 rather than NO2 preferentially permeates through the SSZ-13 membrane with a high SO2 permeance of 2 × 10-7 mol m-2 s-1 Pa-1 and high SO2/NO2 separation factor of 22, ∼50-fold of that measured without dimerization. The dimerization effect for SO2/NO2 separation prevails in other small-pore zeolites such as NaA. This advanced function is revealed through membrane separation using single and mixture gases.

Separation of SO2 and NO2 with the Zeolite Membrane: Molecular Simulation Insights into the Advantageous NO2 Dimerization Effect.

NO2 and SO2, as valuable chemical feedstock, are worth being recycled from flue gases. The separation of NO2 and SO2 is a key process step to enable practical deployment. This work proposes SO2 separation from NO2 using chabazite zeolite (SSZ-13) membranes and provides insights into the feasibility and advantages of this process using molecular simulation. Grand canonical ensemble Monte Carlo and equilibrium molecular dynamics methods were respectively adopted to simulate the adsorption equilibria and diffusion of SO2, NO2, and N2O4 on SSZ-13 at varying Si/Al (1, 5, 11, 71, +∞), temperatures (248-348 K), and pressures (0-100 kPa). The adsorption capacity and affinity (SO2 > N2O4 > NO2) demonstrated strong competitive adsorption of SO2 based on dual-site interactions and significant reduction in NO2 adsorption due to dimerization in the ternary gas mixture. The simulated order of diffusivity (NO2 > SO2 > N2O4) on SSZ-13 demonstrated rapid transport of NO2, strong temperature dependence of SO2 diffusion, and the impermeability of SSZ-13 to N2O4. The membrane permeability of each component was simulated, rendering a SO2/NO2 membrane separation factor of 26.34 which is much higher than adsorption equilibrium (6.9) and kinetic (2.2) counterparts. The key role of NO2-N2O4 dimerization in molecular sieving of SO2 from NO2 was addressed, providing a facile membrane separation strategy at room temperature.

To roll or not to roll: nyctinastic behavior in young leaves of sacred lotus, Nelumbo nucifera.

Foliar nyctinasty refers to the daily rhythm in leaf orientation that occurs in evolutionarily diverse taxa. Traditionally, two mechanisms have been identified for the sleep movement of leaves, namely pulvinar and non-pulvinar. Here, we report upon some novel aspects of the nyctinastic behavior of leaves of the sacred lotus (Nelumbo nucifera Gaertn., Nelumbonaceae). We discovered that expanding leaves underwent daily oscillations in leaf orientation with a more vertical position at night, which is similar to many nyctinastic species. Additionally, however, the immature leaves were observed to exhibit a second type of nyctinasty that involved nocturnal rolling of leaf blades, which has not previously been reported. These two distinct mechanisms acted synergistically to make the young leaves more compact at night during a brief period (6 days) of leaf ontogenesis, during which petiole and blade showed substantial growth. We propose that the nyctinastic behavior of immature N. nucifera leaves is an adaptation that facilitates leaf growth at night by reducing mechanical interference with other leaves and plants.

A novel Fe/Mo co-catalyzed graphene-based nanocomposite to activate peroxymonosulfate for highly efficient degradation of organic pollutants.

A novel 3D α-FeOOH@MoS2/rGO nanocomposite was successfully fabricated by a simple in situ hydrothermal method. It is a highly efficient heterogeneous catalyst in activation of peroxymonosulfate (PMS) for rapid degradation of rhodamine B (RhB), with 99.9% of RhB removed within 20 min. The introduction of rGO contributes to uniform dispersion and sufficient contact of α-FeOOH and MoS2 nanosheets. Highly active Mo(IV) enhances the reduction of Fe(III), improves Fe(III)/Fe(II) conversion and promotes the generation of O21, which ensures an improved catalytic activity. MoS2/rGO hybrid can effectively solve the problem of material reunion and make α-FeOOH exhibit excellent catalytic performance. The α-FeOOH@MoS2-rGO/PMS system is a co-catalytic system based on the active components of α-FeOOH and MoS2. The main reactive oxygen species in the α-FeOOH@MoS2-rGO/PMS system are O21, SO4.- and ⋅O2-, which contribute to a high reactivity over a wide range of pH (5-9). Besides, this system is highly resistant to anions (Cl-, SO42-) and natural organic matter (humic acid), and can be widely used for degradation of common organic pollutants. The α-FeOOH@MoS2/rGO is a promising Fenton-like catalyst for refractory organic wastewater treatment.

A potent synthetic nanobody with broad-spectrum activity neutralizes SARS-CoV-2 virus and the Omicron variant BA.1 through a unique binding mode.

The major challenge to controlling the COVID pandemic is the rapid mutation rate of the SARS-CoV-2 virus, leading to the escape of the protection of vaccines and most of the neutralizing antibodies to date. Thus, it is essential to develop neutralizing antibodies with broad-spectrum activity targeting multiple SARS-CoV-2 variants. Here, we report a synthetic nanobody (named C5G2) obtained by phage display and subsequent antibody engineering. C5G2 has a single-digit nanomolar binding affinity to the RBD domain and inhibits its binding to ACE2 with an IC50 of 3.7 nM. Pseudovirus assays indicated that monovalent C5G2 could protect the cells from infection with SARS-CoV-2 wild-type virus and most of the viruses of concern, i.e., Alpha, Beta, Gamma and Omicron variants. Strikingly, C5G2 has the highest potency against Omicron BA.1 among all the variants, with an IC50 of 4.9 ng/mL. The cryo-EM structure of C5G2 in complex with the spike trimer showed that C5G2 binds to RBD mainly through its CDR3 at a conserved region that does not overlap with the ACE2 binding surface. Additionally, C5G2 binds simultaneously to the neighboring NTD domain of the spike trimer through the same CDR3 loop, which may further increase its potency against viral infection. Third, the steric hindrance caused by FR2 of C5G2 could inhibit the binding of ACE2 to RBD as well. Thus, this triple-function nanobody may serve as an effective drug for prophylaxis and therapy against Omicron as well as future variants.

Effect of loading history on material properties of human heel pad: an in-vivo pilot investigation during gait.

BACKGROUND: This study was aimed to develop a novel dynamic measurement technique for testing the material properties and investigating the effect of continuous compression load on the structural and mechanical properties of human heel pad during actual gait. METHODS: The dual fluoroscopic imaging system (DFIS) and dynamic foot-ground contact pressure-test plate were used for measuring the material properties, including primary thickness, peak strain, peak stress, elastic modulus, viscous modulus and energy dissipation rate (EDR), both at time zero and following continuous loading. Ten healthy pilot subjects, aged from 23 to 72 (average: 46.5 ± 17.6), were enrolled. A "three-step gait cycle" is performed for all subjects, with the second step striking at a marked position on the force plate with the heel to maintain the location of the tested foot to be in the view of fluoroscopes. The subjects were measured at both relaxed (time-zero group) and fatigue (continuous-loading group) statuses, and the left and right heels were measured using the identical procedures. RESULTS: The peak strain, peak stress, elastic modulus, and EDR are similar before and after continuous load, while the viscous modulus was significantly decreased (median: 43.9 vs. 20.37 kPa•s; p < 0.001) as well as primary thicknesses (median: 15.99 vs. 15.72 mm; p < 0.001). Age is demonstrated to be moderately correlated with the primary thicknesses both at time zero (R = -0.507) and following continuous load (R = -0.607). The peak stress was significantly correlated with the elastic modulus before (R = 0.741) and after continuous load (R = 0.802). The peak strain was correlated with the elastic modulus before (R = -0.765) and after continuous load (R = -0.801). The correlations between the viscous modulus and peak stress/ peak strain are similar to above(R = 0.643, 0.577, - 0.586 and - 0.717 respectively). The viscous modulus is positively correlated with the elastic modulus before (R = 0.821) and after continuous load (R = 0.784). CONCLUSIONS: By using dynamic fluoroscopy combined with the plantar pressure plate, the in vivo viscoelastic properties and other data of the heel pad in the actual gait can be obtained. Age was negatively correlated with the primary thickness of heel pad and peak strain, and was positively correlated with viscous modulus. Repetitive loading could decrease the primary thickness of heel pad and viscous modulus.