The receptor binding domain of SARS-CoV-2 Omicron subvariants targets Siglec-9 to decrease its immunogenicity by preventing macrophage phagocytosis.

The development of a vaccine specific to severe acute respiratory syndrome coronavirus 2 Omicron has been hampered due to its low immunogenicity. Here, using reverse mutagenesis, we found that a phenylalanine-to-serine mutation at position 375 (F375S) in the spike protein of Omicron to revert it to the sequence found in Delta and other ancestral strains significantly enhanced the immunogenicity of Omicron vaccines. Sequence FAPFFAF at position 371-377 in Omicron spike had a potent inhibitory effect on macrophage uptake of receptor-binding domain (RBD) nanoparticles or spike-pseudovirus particles containing this sequence. Omicron RBD enhanced binding to Siglec-9 on macrophages to impair phagocytosis and antigen presentation and promote immune evasion, which could be abrogated by the F375S mutation. A bivalent F375S Omicron RBD and Delta-RBD nanoparticle vaccine elicited potent and broad nAbs in mice, rabbits and rhesus macaques. Our research suggested that manipulation of the Siglec-9 pathway could be a promising approach to enhance vaccine response.

A Mosaic Nanoparticle Vaccine Elicits Potent Mucosal Immune Response with Significant Cross-Protection Activity against Multiple SARS-CoV-2 Sublineages.

Because of the rapid mutation and high airborne transmission of SARS-CoV-2, a universal vaccine preventing the infection in the upper respiratory tract is particularly urgent. Here, a mosaic receptor-binding domain (RBD) nanoparticle (NP) vaccine is developed, which induces more RBD-targeted type IV neutralizing antibodies (NAbs) and exhibits broad cross-protective activity against multiple SARS-CoV-2 sublineages including the newly-emerged BF.7, BQ.1, XBB. As several T-cell-reactive epitopes, which are highly conserved in sarbecoviruses, are displayed on the NP surface, it also provokes potent and cross-reactive cellular immune responses in the respiratory tissue. Through intranasal delivery, it elicits robust mucosal immune responses and full protection without any adjuvants. Therefore, this intranasal mosaic NP vaccine can be further developed as a pan-sarbecovirus vaccine to block the viral entrance from the upper respiratory tract.

Performance enhancement of the soft robotic segment for a trunk-like arm.

Trunk-like continuum robots have wide applications in manipulation and locomotion. In particular, trunk-like soft arms exhibit high dexterity and adaptability very similar to the creatures of the natural world. However, owing to the continuum and soft bodies, their performance in payload and spatial movements is limited. In this paper, we investigate the influence of key design parameters on robotic performance. It is verified that a larger workspace, lateral stiffness, payload, and bending moment could be achieved with adjustments to soft materials' hardness, the height of module segments, and arrayed radius of actuators. Especially, a 55% increase in arrayed radius would enhance the lateral stiffness by 25% and a bending moment by 55%. An 80% increase in segment height would enlarge 112% of the elongation range and 70 % of the bending range. Around 200% and 150% increments in the segment's lateral stiffness and payload forces, respectively, could be obtained by tuning the hardness of soft materials. These relations enable the design customization of trunk-like soft arms, in which this tapering structure ensures stability via the stocky base for an impact reduction of 50% compared to that of the tip and ensures dexterity of the long tip for a relatively larger bending range of over 400% compared to that of the base. The complete methodology of the design concept, analytical models, simulation, and experiments is developed to offer comprehensive guidelines for trunk-like soft robotic design and enable high performance in robotic manipulation.

"Gloppiness" Phenomena and a Computer Vision Method to Quantify It.

In this study, we present a rapid, cost-effective Python-driven computer vision approach to quantify the prevalent "gloppiness" phenomenon observed in complex fluids and gels. We discovered that rheology measurements obtained from commercial shear rheometers do show some hints, but do not exhibit a strong correlation with the extent of "gloppiness". To measure the "gloppiness" level of laboratory-produced shower gel samples, we employed the rupture time of jetting flow and found a significant correlation with data gathered from the technical insight panelist team. While fully comprehending the "gloppiness" phenomenon remains a complex challenge, the Python-based computer vision technique utilizing jetting flow offers a promising, efficient, and affordable solution for assessing the degree of "gloppiness" for commercial liquid and gel products in the industry.

Application of Allogeneic Human Acellular Dermal Matrix Reduces the Incidence of Fistula in Hypospadias Repair.

Background: Urethrocutaneous fistula is one of the most common complications arising from hypospadias surgery. The purpose of our study was to investigate the effectiveness and safety of allogeneic human acellular dermal matrix (HADM) application as a means of preventing the occurrence of urethrocutaneous fistula following hypospadias surgery. Methods: This is a non-randomized study of 219 cases (out of 270 patients with hypospadias) which satisfied inclusion and exclusion criteria. These patients were divided into two groups: 101 HADM patients, and 118 control patients (who did not receive HADM). In the control group, 77 boys were treated by single-stage urethroplasty (TIP) and 41 underwent staged urethroplasty (Thiersch-Duplay). In the HADM group, 59 boys underwent the TIP and 42 underwent the Thiersch-Duplay. In the postoperative period, we recorded the incidence of infection, urethrocutaneous fistula, and urethral stricture complications in these two groups of patients. The effectiveness and safety of HADM in preventing urethrocutaneous fistula following hypospadias surgery were evaluated according to these indicators. Results: In the control group, following the operation there were 16 cases of infection, 38 cases of urethrocutaneous fistula after extubating, and 5 cases of urethral stricture. In the HADM group, there were 19 cases of postoperative infection, 12 cases of urethrocutaneous fistula after extubating, and 5 children with urethral stricture. In comparing the two groups, it was found that the postoperative infection rate (13.6 vs. 18.8%) and the incidence of urethral stricture (4.2 vs. 5.0%) were not statistically significant (P > 0.05), while the postoperative urethrocutaneous fistula rate (32.2 vs. 11.9%) was statistically significant (P < 0.001). Conclusion: It is found that HADM application can significantly reduce the incidence of urethrocutaneous fistula complications, without increasing the risk of infection and urethral stricture.

Development of Receptor Binding Domain (RBD)-Conjugated Nanoparticle Vaccines with Broad Neutralization against SARS-CoV-2 Delta and Other Variants.

The SARS-CoV-2 Delta (B.1.617.2) strain is a variant of concern (VOC) that has become the dominant strain worldwide in 2021. Its transmission capacity is approximately twice that of the original strain, with a shorter incubation period and higher viral load during infection. Importantly, the breakthrough infections of the Delta variant have continued to emerge in the first-generation vaccine recipients. There is thus an urgent need to develop a novel vaccine with SARS-CoV-2 variants as the major target. Here, receptor binding domain (RBD)-conjugated nanoparticle vaccines targeting the Delta variant, as well as the early and Beta/Gamma strains, are developed. Under both a single-dose and a prime-boost strategy, these RBD-conjugated nanoparticle vaccines induce the abundant neutralizing antibodies (NAbs) and significantly protect hACE2 mice from infection by the authentic SARS-CoV-2 Delta strain, as well as the early and Beta strains. Furthermore, the elicitation of the robust production of broader cross-protective NAbs against almost all the notable SARS-CoV-2 variants including the Omicron variant in rhesus macaques by the third re-boost with trivalent vaccines is found. These results suggest that RBD-based monovalent or multivalent nanoparticle vaccines provide a promising second-generation vaccine strategy for SARS-CoV-2 variants.

USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID.

Activation-induced cytidine deaminase (AID) initiates class-switch recombination and somatic hypermutation (SHM) in antibody genes. Protein expression and activity are tightly controlled by various mechanisms. However, it remains unknown whether a signal from the extracellular environment directly affects the AID activity in the nucleus where it works. Here, we demonstrated that a deubiquitinase USP10, which specifically stabilizes nuclear AID protein, can translocate into the nucleus after AKT-mediated phosphorylation at its T674 within the NLS domain. Interestingly, the signals from BCR and TLR1/2 synergistically promoted this phosphorylation. The deficiency of USP10 in B cells significantly decreased AID protein levels, subsequently reducing neutralizing antibody production after immunization with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or human immunodeficiency virus type 1 (HIV-1) nanoparticle vaccines. Collectively, we demonstrated that USP10 functions as an integrator for both BCR and TLR signals and directly regulates nuclear AID activity. Its manipulation could be used for the development of vaccines and adjuvants.

Stationary monitoring and source apportionment of VOCs in a chemical industrial park by combining rapid direct-inlet MSs with a GC-FID/MS.

Fast and comprehensive monitoring of VOCs, required for air quality management in large-scale chemical industrial parks in China, cannot be accomplished by stationary measurements using conventional GC-FID or GC-MS alone due to their low temporal resolutions and limited detectable ranges. Novel direct-inlet mass spectrometry (DI-MS) has been widely applied for real-time monitoring of VOCs. To verify its applicability in industrial settings, high mass-resolution proton-transfer-reaction time-of-flight MS (HMR-PTR-TOFMS), single-photon ionization time-of-flight MS (SPI-TOFMS), together with online GC-FID/MS were simultaneously deployed at the boundary of one of the largest chemical industrial parks in eastern China. Aromatics, acetonitrile, acetic acid, ethyl acetate, aliphatic hydrocarbons, 1,2-dichloroethane, and acetone were detected as the main pollutants. These three instruments detected 12 common species, among which ethyl acetate, toluene, C8-aromatics, and methyl ethyl ketone showed similar time series and levels. Acetone, benzene, chlorobenzene, styrene, and C9-aromatics showed only similar time series. The HMR-PTR-TOFMS uniquely detected 14 species, mainly oxidized VOCs, nitriles, and amines, which greatly helps acknowledge the pollutants in the chemical industrial area. Positive matrix factorization, using the HMR-PTR-TOFMS and GC-FID/MS datasets, was used to identify eight sources. Four of the identified sources were mainly detected by the HMR-PTR-TOFMS, with pollutants mainly comprised of nitriles, amines, carbonyls, and organic acids, most of which were hazardous and/or odorous. These four sources accounted for 41.5% and 33.2% of the total VOCs and ozone formation potential, respectively. The complementary nature of GC-FID/MS and HMR-PTR-TOFMS in VOC source apportionment in industrial settings is of great practical use for advanced VOCs abatement. Thus, the high mass resolution DI-MSs are suggested to be a supplementary measurement for fence-line monitoring. Although with a relatively short period attempt, this study has wide implications for the fence-line stationary observational modes and source apportion methods combining with traditional observations.

Simulated aeromedical evacuation exacerbates burn induced lung injury: targeting mitochondrial DNA for reversal.

BACKGROUND: Aeromedical evacuation of patients with burn trauma is an important transport method in times of peace and war, during which patients are exposed to prolonged periods of hypobaric hypoxia; however, the effects of such exposure on burn injuries, particularly on burn-induced lung injuries, are largely unexplored. This study aimed to determine the effects of hypobaric hypoxia on burn-induced lung injuries and to investigate the underlying mechanism using a rat burn model. METHODS: A total of 40 male Wistar rats were randomly divided into four groups (10 in each group): sham burn (SB) group, burn in normoxia condition (BN) group, burn in hypoxia condition (BH) group, and burn in hypoxia condition with treatment intervention (BHD) group. Rats with 30% total body surface area burns were exposed to hypobaric hypoxia (2000 m altitude simulation) or normoxia conditions for 4 h. Deoxyribonuclease I (DNase I) was administered systemically as a treatment intervention. Systemic inflammatory mediator and mitochondrial deoxyribonucleic acid (mtDNA) levels were determined. A histopathological evaluation was performed and the acute lung injury (ALI) score was determined. Malonaldehyde (MDA) content, myeloperoxidase (MPO) activity, and the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome level were determined in lung tissues. Data among groups were compared using analysis of variance followed by Tukey's test post hoc analysis. RESULTS: Burns resulted in a remarkably higher level of systemic inflammatory cytokines and mtDNA release, which was further heightened by hypobaric hypoxia exposure (P < 0.01). Moreover, hypobaric hypoxia exposure gave rise to increased NLRP3 inflammasome expression, MDA content, and MPO activity in the lung (P < 0.05 or P < 0.01). Burn-induced lung injuries were exacerbated, as shown by the histopathological evaluation and ALI score (P < 0.01). Administration of DNase I markedly reduced mtDNA release and systemic inflammatory cytokine production. Furthermore, the NLRP3 inflammasome level in lung tissues was decreased and burn-induced lung injury was ameliorated (P < 0.01). CONCLUSIONS: Our results suggested that simulated aeromedical evacuation further increased burn-induced mtDNA release and exacerbated burn-induced inflammation and lung injury. DNase I reduced the release of mtDNA, limited mtDNA-induced systemic inflammation, and ameliorated burn-induced ALI. The intervening mtDNA level is thus a potential target to protect from burn-induced lung injury during aeromedical conditions and provides safer air evacuations for severely burned patients.

Linear versus branched: flow of a wormlike micellar fluid past a falling sphere.

We report experiments on flow of wormlike micellar solutions past a falling sphere. By increasing the salt-to-surfactant concentration ratio, and beyond a viscosity peak, wormlike micelles experience a transition from linear to branched microstructure. Two viscoelastic wormlike micelles with salt to surfactant concentrations on each side of the viscosity peak are considered. Our results indicate three significant differences in flows of branched and linear micelles. First, while the sphere drag correction factor rapidly decreases upon increasing Weissenberg number in linear micelles, it shows an apparent local maximum at Wi ≈ 3 in branched micelles. Second, despite its high viscoelasticity, the time-averaged flow of branched micelles around the falling sphere exhibits a fore-and-aft symmetry, while a strong negative wake is observed in linear micelles at relatively weaker flows. Third, branched micelles exhibit a stronger flow-induced birefringence than linear micelles in an otherwise identical condition. Our hypothesis is that subject to strong flows around the falling sphere, branched micelles can relax much more efficiently than linear wormlike micelles through sliding of the branched junctions. This additional stress relaxation mechanism may facilitate micellar orientation, produce a marginal sphere drag reduction and a Newtonian-like flow profile around the falling sphere. Finally, unsteady flow is observed in both linear and branched micellar solutions beyond some critical thresholds of the extensional Weissenber number. Our results corroborate a recently proposed criterion for onset of instability in flow of wormlike micelles past a falling sphere, thereby, suggesting that micellar branching does not affect the mechanism of flow instability.

Genetic association between cluster of differentiation 86 variations and sepsis risk: A case-control study.

The aim of this study was to investigate the correlation between cluster of differentiation 86 (CD86) gene rs1129055 and rs2715267 single nucleotide polymorphisms and sepsis susceptibility.One hundred twenty-five sepsis patients and 120 healthy controls were enrolled in this case-control study. CD86 polymorphisms rs1129055 and rs2715267 were genotyped through polymerase chain reaction-restriction fragment length polymorphism approach. Chi-square test was used to analyze differences in genotype and allele frequencies of the 2 polymorphisms between case and control groups. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to present the association strength of the polymorphisms with sepsis susceptibility.AA genotype and A allele frequencies of CD86 rs1129055 were significantly lower in sepsis patients than in healthy controls (P < .05), revealing their significant associations with decreased disease susceptibility (OR = 0.351, 95% CI = 0.169-0.728; OR = 0.593, 95% CI = 0.415-0.847). Nevertheless, rs2715267 had no significant association with sepsis susceptibility (P > .05).AA genotype and A allele of CD86 polymorphism rs1129055 might be correlated with decreased sepsis susceptibility in Chinese Han population, but not rs2715267. Further study should be performed to verify our findings.

Characterization of rabbit urine-derived stem cells for potential application in lower urinary tract tissue regeneration.

Tissue-engineered urethra with autologous cells seeded on biodegradable scaffolds offers an alternative for lower urinary tract reconstruction. Rabbit is most commonly used as an animal model in urethra and bladder tissue repair. The goal of this study is to characterize rabbit urine-derived stem cells (rUSC) and induce these cells to differentiate into urothelial and smooth muscle cells as an autologous cell source for potential use in lower urinary tract tissue regeneration in a rabbit model. We successfully cultured rUSC from 12 urine samples and 13 bladder wash samples of six rabbits. rUSC colonies appeared more in the bladder wash solution (2-4/15 ml) than those in the urine samples (1-2 clones/15 ml urine). The cells displayed rice grain-like in morphology. Mean population doubling of rUSC was 48.5 ± 6.2 and average doubling time was 25.7 ± 8.4 h, indicating that a single of rUSC clone generated about 4 × 1014 cells in 50 days. The rUSC were positive for CD29, CD90 and CD105 but negative for CD31, CD34 and CD45 in flow cytometry. When exposed to PDGF-BB and TGF-ß1, these cells could differentiate into spindle-like cells, expressing smooth muscle-specific proteins, including α-smooth muscle action, desmin and myosin. Urothelially differentiated rUSC expressed urothelial-specific proteins, i.e., AE1/AE3 and E-cadherin when exposed to epidermal growth factor (EGF). Osteogenic-differentiated rUSC expressed osteogenic marker, i.e., alkaline phosphatase when exposed to serum containing DMEM low-glucose medium with osteogenic supplements. In conclusion, rUSC can be isolated from bladder wash or urine samples and cultured in vitro. There stem cells possess strong proliferative ability and are capable of differentiating in urothelial, myogenic and osteogenic lineages. Thus, rUSC are a potential alternative autologous cell source for lower urinary tract repair with tissue engineering technology in a rabbit model.

Colorimetric aptasensor for progesterone detection based on surfactant-induced aggregation of gold nanoparticles.

This paper proposes an aptasensor for progesterone (P4) detection in human serum and urine based on the aggregating behavior of gold nanoparticles (AuNPs) controlled by the interactions among P4-binding aptamer, target P4 and cationic surfactant hexadecyltrimethylammonium bromide (CTAB). The aptamer can form an aptamer-P4 complex with P4, leaving CTAB free to aggregate AuNPs in this aptasensor. Thus, the sensing solution will turn from red (520 nm) to blue (650 nm) in the presence of P4 because P4 aptamers are used up firstly owing to the formation of an aptamer-P4 complex, leaving CTAB free to aggregate AuNPs. However, in the absence of P4, CTAB combines with aptamers so that AuNPs still remain dispersed. Therefore, this assay makes it possible to detect P4 not only by absorbance measurement but also through naked eyes. By monitoring the variation of absorbance and color, a CTAB-induced colorimetric assay for P4 detection was established with a detection limit of 0.89 nM. Besides, the absorbance ratio A650/A520 has a linear correlation with the P4 concentration of 0.89-500 nM. Due to the excellent recoveries in serum and urine, this biosensor has great potential with respect to the visual and instrumental detection of P4 in biological fluids.

Radical Departure: Thermally-Triggered Degradation of Azo-Containing Poly(ß-thioester)s.

The design and synthesis of a new class of thermally-labile poly(ß-thioester)s is reported. Aliphatic azo linkages were incorporated into the main chain of the polymers to allow for degradation to lower molecular weights upon heating. These polymers displayed a temperature-dependent degradation profile with a significant increase in decomposition rate as the temperature was raised from 60 to 95 °C. This approach was further extended to prepare amphiphilic triblock copolymers containing poly(ß-thioester)s and poly(ethylene glycol) (PEG). The resulting block copolymers were capable of self-assembly into micelles in water. Moreover, the assembled nanoparticles underwent dissociation as a result of exposure to heat.

Multiresidue determination of organophosphorus pesticides in solid waste environmental samples by gas chromatography.

The method for the determination of 12 organophosphorus pesticides in solid waste was established. The organophosphorus pesticides were analyzed by Soxhlet extraction or accelerated solvent extraction (ASE)-SPE cartridge-flame photometric detector (FPD), and leaching solution by rotary oscillation-positive pressure filtration-liquid-liquid extraction-SPE cartridge-FPD. The differences of extraction efficiencies between Soxhlet and ASE were compared. Solvent of Soxhlet extraction, purification and recovery of organophosphorus pesticides in leaching conditions were also studied. The recoveries were 54.2-119.8%, and the average recovery was 87.7%. The RSD was 1.89-9.10% (n = 6), the average RSD was 6.88%, and the detection limit was 0.27-0.69 µg/kg.

[Analysis and prevention of postoperative complications of tubularized incised plate urethroplasty for hypospadia].

OBJECTIVE: To explore the reasons and preventions of complications of tubularized incised plate urethroplasty technique for hypospadia repair. METHODS: In the study, 54 patients of 247 hypospadia patients were analyzed who had complications, using SPSS 13.0 statistics to compare their complications with anatomy reasons including positions of the meatus, development of urethral mucous membrane and glans penis and degrees of ventral curvature. RESULTS: (1) Postoperative complications were relative to the position of meatus. The closer urinary meatus was to the coronary sulcus, the higher complication rate would be(χ(2)=26.309, P<0.01).( 2) The complication rate of normal glans penis was lower than that of the small glans penis (χ(2)=23.709, P<0.01). (3) The well developed urethral mucous membrane had a lower complication rate(χ(2)=12.086, P<0.01). (4) When the angle of ventral curvature was larger than 30°, a higher complication rate occurred(χ(2)=10.233, P<0.01). CONCLUSION: Tubularized incised plate urethroplasty procedure for single-stage urethroplasty is the first choice for patients with big glans penis, normal development of urethral plate and slight curvature so as to achieve high curing rates and good shape of penis.

[Combination of compound Xuanju Capsule and sildenafil for erectile dysfunction that progressively fails to respond to sildenafil].

OBJECTIVE: To explore the clinical effects of Compound Xuanju Capsule (CXC) combined with sildenafil on erectile dysfunction (ED) that progressively fails to respond to sildenafil. METHODS: Totally, 36 ED patients who progressively failed to respond to sildenafil were randomly divided into a trial and a control group of equal number, the former treated with oral CXC at 3 g tid plus sildenafil at 50 mg an hour before sexual activity, while the latter with sildenafil alone at 100 mg an hour before sexual activity. After 2 months of treatment, we compared the patients' scores on IIEF-5 and their partners' scores on Treatment Satisfaction Scale (TSS) between the two groups. RESULTS: The total rate of erectile function improvement was 94.44% in the trial and 88.89% in the control group (P > 0.05). The IIEF-5 score was 20.888 9 +/- 3.833 1 in the former and 18. 777 8 +/- 4.008 2 in the latter after treatment, significantly higher than 13. 166 7 +/- 3.601 5 and 13. 055 6 +/- 2.775 4 before treatment (P < 0.05). The post-treatment IIEF-5 scores of the patients and the TSS scores of their partners were markedly higher in the trial than in the control group (P < 0.05). CONCLUSION: Compound Xuanju Capsule combined with sildenafil is effective for erectile dysfunction that progressively fails to respond to sildenafil.

[Application of tubularized incised plate in one-stage urethroplasty for hypospadia accompanied with anatomic kak-factors].

OBJECTIVE: To investigate the application of tubularized incised plate (TIP) in urethroplasty for hypospadia accompanied with anatomic kak-factors. METHODS: We retrospectively studied 191 cases of hypospadia treated by one-stage TIP urethroplasty. Taking the position of the urinary meatus, the development of the glans penis and urethral plate, and the degree of penile ventral curvature as anatomic kak-factors inducing postoperative complications and affecting the appearance, we conducted correlation analyses on the clinical effects of the procedure using SPSS 10.0 statistics. RESULTS: Postoperative complications were closely correlated with the position of the urinary meatus, the nearer its position to the coronary sulcus, the higher the incidence of complications (chi2 = 24.291, P < 0.01). And so were they with the development of the glans penis and urethral plate and the degree of penile ventral curvature. The incidence of postoperative complications was significantly higher in the hypospadia patients with small glans, maldeveloped urethral plate and severe penile ventral curvature than in those with straight penis and well-developed glans and urethral plate (chi2 = 25.419, P < 0.01). CONCLUSION: Tubularized incised plate urethroplasty for hyper-spadias should be chosen according to the position of the meatus, the development of urethral mucous membrane, the degree of ventral curvature and surgery experience in order to achieve a high cure rate and good cosmetic effect.