Adverse effect of TWPs on soil fungi and the contribution of benzothiazole rubber additives.

Tire wear particles (TWPs) pollution is widely present in soil, especially in areas severely affected by traffic. Herein, regular variation of fungal biomass with TWPs was found in soils with different distances from the highway. In addition, the concentrations of benzothiazole compounds (BTHs), an important class of rubber vulcanization accelerators, were found to be positively correlated to the TWPs abundance. Sixty days' soil microcosm experiments were conducted to further confirm the adverse effect of TWPs and BTHs on soil fungi. TWPs spiking at 1000 mg/kg, a detectable level in the roadside, resulted in significant reduction of biomass and significant changes of soil fungal community structure, with Eurotium and Polyporales being the sensitive species. BTH+ 2-hydroxybenzothiazole (OHBT) (the dominant BTHs in soil) spiking at 200 ng/kg, the dose equivalent to 1000 mg/kg TWPs pollution, also caused a similar magnitude of soil fungal biomass reduction. Adonis demonstrated no significant difference of fungal community structure between TWPs and BTH+OHBT spiked soil, suggesting the adverse effect of TWPs on soil fungi may be explained by the act of BTHs. Pure culture using the representative soil fungi Eurotium and Polyporales also confirmed that BTHs were the main contributors to the adverse effect of TWPs on soil fungi.

Hydrogels with high sacrifice efficiency of sacrificial bonds and with high strength and toughness due to dense entanglements of polymer chains.

Introducing sacrificial bonds is a common method for increasing the toughness of hydrogels. Many sacrificial bonds have been extensively investigated, but the sacrifice efficiency has never been studied. In this study, polyacrylamide hydrogels with highly entangled polymer chains containing carboxyl-zirconium (-COO--Zr4+) sacrificial bonds are prepared to study the effect of polymer chain entanglement on the sacrificial bond efficiency. Unlike chemical crosslinking points, the dense physical entanglements do not affect the toughness (∼43 MJ/m3) of hydrogels but significantly improve the tensile strength (by two times) and Young's modulus (by six times). Physical entanglements enable the chains to slide and adjust the network structure under stress, which enables more polymer chains and sacrificial bonds to participate in the deformation process. Therefore, dense entanglements will greatly improve the sacrifice efficiency. However, a high density of chemical crosslinking points will limit the improvement in the sacrifice efficiency, which is attributed to the sliding limitations because of physical entanglement. The highly entangled polyacrylamide hydrogels toughened by -COO--Zr4+ have an excellent load-bearing capacity. This study provides a novel strategy for designing hydrogels with ultra-high strength and toughness, which paves the way for the development of many hydrogels used in engineering materials.

Alpaca-derived nanobody targeting the hydrophobic pocket of the HIV-1 gp41 NHR broadly neutralizes HIV-1 by blocking six-helix bundle formation.

The highly conserved hydrophobic pocket region of HIV-1 gp41 NHR triple-stranded coiled coil is crucial for the binding of CHR to NHR to form a six-helix bundle (6-HB). This pocket is only exposed instantaneously during fusion, making it an ideal target for antibody drug design. However, IgG molecule is too big to enter the pocket during the fusion process. Therefore, to overcome the steric hindrance and kinetic obstacles caused by the formation of gp41 pre-hairpin fusion intermediate, we obtained nanobodies (Nbs) targeting NHR by immunizing alpaca with an NHR-trimer mimic. Specifically, we identified a Nb, Nb-172, that exhibited potent and broadly neutralizing activity against HIV-1 pseudoviruses, HIV-1 primary isolates, and T20-resistant HIV-1 strains. In addition, the combinatorial use of mD1.22 and Nb-172 exhibited synergism in inhibiting HIV-1 infection inactivating cell-free virions. Nb-172 can competitively bind to the hydrophobic pocket of gp41 NHR to inhibit 6-HB formation. These findings suggest that Nb-172 merits further investigation as a potential therapeutic for HIV-1 infection.

Associations of Cadmium Exposure with Peripheral Blood Cell Subtype Counts and Indices in Cadmium-Poisoned Mice.

This research was designed to investigate the effects of cadmium on blood cell injury in cadmium-poisoned mice. Twenty mice were randomly divided into two groups: control group and model group. The control group was intraperitoneally injected with normal saline every day and the model group was intraperitoneally injected with 1.4 mg/kg cadmium solution every day. The experimental period was 28 days. The blood of the mice was collected for detection and hematological analysis. The results demonstrated that cadmium increased the number of white blood cells and the number of neutrophils in mice. Cadmium reduced the number of eosinophils, the number of basophils, the number of monocytes, the amount of lymphocytes, the number of red blood cells, the hemoglobin concentration, mean corpusular volume, mean corpusular hemoglobin, mean corpusular hemoglobin concentration, and the number of platelets in mice. In summary, cadmium caused some damage to white blood cells, red blood cells, and platelets in mice, but the direction of damage to different cells was inconsistent. The possible reason for this result is that cadmium damages the generation of blood cells, and the body takes corresponding defense measures.

Effect of cadmium on histopathological injuries and ultra-structural changes of kidney of the turtle Mauremys reevesii.

This research investigated the effect of cadmium on the tissue and cell of kidney of the turtle Mauremys reevesii. Twenty turtles were injected with cadmium at 0, 7.5, 15, 30 mg/kg separately and five turtles were taken in each group at two weeks after exposure. Kidneys were immediately excised and macroscopic pathological changes were observed, then the kidneys were fixed in 4% paraformaldehyde for histopathological examination and fixed in 2.5% (v/v) glutaraldehyde for examination of ultra-structure. The tissues of kidney presented varying degrees of histopathological lesions in cadmium treated turtles by a dose-dependent manner under the light microscope. Under transmission electron microscope, renal tubules cells presented varying degrees of dose-dependent lesions. The results indicated that cadmium can cause cell damages to the kidney, in particular to the mitochondria. Mitochondria can be used as one biomarker in the monitoring of cadmium pollution and its quantitative risk assessments.

Rapid, sensitive, and user-friendly detection of Pseudomonas aeruginosa using the RPA/CRISPR/Cas12a system.

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is a life-threatening bacterium known for its rapid development of antibiotic resistance, posing significant challenges in clinical treatment, biosecurity, food safety, and environmental monitoring. Early and accurate identification of P. aeruginosa is crucial for effective intervention. METHODS: The lasB gene of P. aeruginosa was selected as the target for the detection. RPA primers for recombinase polymerase amplification (RPA) and crRNA for CRISPR/Cas12a detection were meticulously designed to target specific regions within the lasB gene. The specificity of the RPA/CRISPR/Cas12a detection platform was assessed using 15 strains. The detection limit of RPA/CRISPR/Cas12a detection platform was determined by utilizing a pseudo-dilution series of the P. aeruginosa DNA. The practical applicability of the RPA/CRISPR/Cas12a detection platform was validated by comparing it with qPCR on 150 samples (35 processed meat product samples, 55 cold seasoned vegetable dishes, 60 bottled water samples). RESULTS: The RPA/CRISPR/Cas12a detection platform demonstrates high specificity, with no cross-reactivity with non-P. aeruginosa strains. This assay exhibits remarkable sensitivity, with a limit of detection (LOD) of 100 copies/µL for fluorescence assay and 101 copies/µL for the LFTS method. Furthermore, the performance of the RPA/CRISPR/Cas12a detection platform is comparable to that of the well-established qPCR method, while offering advantages such as shorter reaction time, simplified operation, and reduced equipment requirements. CONCLUSIONS: The RPA/CRISPR/Cas12a detection platform presents a straightforward, accurate, and sensitive approach for early P. aeruginosa detection and holds great promise for diverse applications requiring rapid and reliable identification.

SARS-CoV-2 evolution from the BA.2.86 to JN.1 variants: unexpected consequences.

SARS-CoV-2 is continuously evolving. The Omicron subvariant BA.2.86, with >30 mutations in its spike (S) protein compared with its predecessor strain BA.2, was expected to quickly become predominant worldwide, but this has not happened. Instead, its descendant strain, JN.1, with just one additional mutation, has become the predominant SARS-CoV-2 subvariant. Here, we offer a possible explanation for these unexpected consequences.

Tough double network hydrogels with rapid self-reinforcement and low hysteresis based on highly entangled networks.

Most tough hydrogels are reinforced by introducing energy dissipation mechanisms, but simultaneously realizing a high toughness and low hysteresis is challenging because the energy dissipation structure cannot recover rapidly. In this work, high mechanical performance highly entangled double network hydrogels without energy dissipation structure are fabricated, in which physical entanglements act as the primary effective crosslinking in the first network. This sliding entanglement structure allows the hydrogel network to form a highly uniform oriented structure during stretching, resulting in a high tensile strength of ~3 MPa, a fracture energy of 8340 J m-2 and a strain-stiffening capability of 47.5 in 90% water content. Moreover, almost 100% reversibility is obtained in this hydrogel via energy storage based on entropy loss. The highly entangled double network structure not only overcomes the typical trade-off between the high toughness and low hysteresis of hydrogels, but more importantly, it provides an insight into the application of entanglement structures in high-performance hydrogels.

Immunotherapy rechallenge of advanced lung adenocarcinoma with cadonilimab (PD-1/CTLA-4 Bi-specific antibody): a case report.

Lung adenocarcinoma (ADC) is a common pulmonary malignant disease with poor prognosis. Immunotherapeutic strategies are the current cornerstone of first-line therapy in driver-negative advanced lung ADC, but there is no treatment standard once the disease has progressed after the first-line application of immune checkpoint inhibitors (ICIs). Clinically, immunotherapy rechallenges are being attempted. However, it is undeniable that there are still great limitations to rechallenging patients with single- or double-ICI immunotherapy though immunotherapy rechallenges can bring new benefits. Cadonilimab (AK104), a unique bi-specific antibody targeting PD-1/CTLA-4, has similar biological activity but lower toxicity than the combination of CTLA-4 and PD-1 antibodies. Herein, we report a case of advanced lung ADC rechallenged with cadonilimab as a posterior-line therapy. The condition of the patient was maintained at stable disease for 6 months. This might provide a new idea and choice for the challenge of immunotherapy resistance.

Natural isoflavone glabridin targets PI3Kγ as an adjuvant to increase the sensitivity of MDA-MB-231 to tamoxifen and DU145 to paclitaxel.

Glabridin is a natural isoflavone with estrogen receptor agonism and significant anti-tumor activity. Additionally, glabridin has a regulation effect on PI3K/AKT/mTOR pathway, but its exact target remains unclear. In this study, we evaluated the antitumor activity of glabridin against breast cancer and prostate cancer cells, and further clarified its targeting to PI3K. We found that glabridin could significantly inhibit the cell viability of human breast cancer and prostate cancer cell lines. It induced caspase activation cascade and cell apoptosis through decreasing the mitochondrial transmembrane potential and increasing the intracellular reactive oxygen species (ROS). Moreover, glabridin could attenuate epithelial-mesenchymal transition (EMT) progression by inhibiting cell migration. PharmMapper calculation showed that PI3Kγ might be the most potential target protein because of the highest Normal Fit score (0.9735) and z'-score (0.9797). Molecular docking and bio-layer interferometry (BLI) analysis further demonstrated the PI3Kγ targeting of glabridin. In vivo experiments showed that glabridin can effectively inhibit the tumor growth of breast cancer xenograft model, and does not show obvious hepatorenal toxicity. Moreover, glabridin could effectively promote the anti-proliferation and pro-apoptotic effects of tamoxifen on MDA-MB-231 cell and taxol on DU145 cell. Elucidating the targeting of glabridin to PI3K may lay a theoretical foundation for the structural derivatization of glabridin, which is expected to greatly promote the application and development of glabridin in the field of cancer therapy.

Universal adhesion using mussel foot protein inspired hydrogel with dynamic interpenetration for topological entanglement.

Achieving adhesion of hydrogels to universal materials with desirable strength remains a challenge despite emerging application of hydrogels. Herein we present a mussel foot protein (Mfp) inspired polyelectrolyte hydrogel of poly(ethylenimine)/poly(acrylic acid)-dopamine (PEI/PAADA) developed for universal tough adhesion. The highly-concentrated electrostatic and hydrogen-bonding interactions in PEI/PAADA hydrogel resulted in a tensile strength, strain at break, and toughness of 0.297 MPa, 2784 % and 5.440 MJ m-3, respectively. Moreover, the hydrogel can heal itself from physical damages, even can be recycled after totally dried via rehydration because of the high flexibility and reversibility of its dynamic bonds. Combining the strategies of topological stitching and direct bonding, Mfp-derived catechol and PEI/PAA backbone in PEI/PAADA corporately facilitated robust adhesion of universal materials with shear strength of up to 4.4 MPa and peeling strength of 870 J m-2, which is over 10 times greater than that of commercial fibrin gel. The adhesive also exhibited self-healing capability for at least 5 cycles, good stability in 1 M NaCl solution and characteristic debonding catalyzed by calcium. Moreover, in vitro cell behavior and in vivo wound healing assays suggested the potential of PEI/PAADA as wound dressing.

Acetolactate Decarboxylase as an Important Regulator of Intracellular Acidification, Morphological Features, and Antagonism Properties in the Probiotic Lactobacillus reuteri.

SCORE: This study identifies the coding gene (aldB) of acetolactate decarboxylase (ALDC) as an important regulatory gene of the intracellular pH in Lactobacillus reuteri (L. reuteri), uncovering the important role of ALDC in regulating intracellular pH, morphological features, and antagonism properties in the probiotic organism L. reuteri. METHODS AND RESULTS: The aldB mutant (ΔaldB) of L. reuteri is established using the homologous recombination method. Compare to the wild-type (WT) strain, the ΔaldB strain shows a smaller body size, grows more slowly, and contains more acid in the cell cytoplasm. The survival rate of the ΔaldB strain is much lower in low pH and simulated gastric fluid (SGF) than that of the WT strain, but higher in simulated intestinal fluid (SIF). The antagonism test demonstrates the ΔaldB strain can inhibit Listeria monocytogenes (L. monocytogenes) and Salmonella more effectively than the WT strain. Additionally, there is a dramatic decrease in the adhesion rate of Salmonella to Caco-2 and HT-29 cells in the presence of the ΔaldB strain compared to the WT strain. Simultaneously analyze, the auto-aggregation, co-aggregation, cell surface hydrophobicity (CSH), hemolytic, temperature, NaCl, oxidative stress, and antibiotic susceptibility of the ΔaldB strain are consistent with the features of probiotics. CONCLUSION: This study highlights that the aldB gene plays a significant role in the growth and antibacterial properties of L. reuteri.

Overcoming the Dilemma of In Vivo Stable Adhesion and Sustained Degradation by the Molecular Design of Polyurethane Adhesives for Bone Fracture Repair.

Bone adhesive is a promising candidate to revolutionize the clinical treatment of bone repairs. However, several drawbacks have limited its further clinical application, such as unreliable wet adhesive performance leading to fixation failure and poor biodegradability inhibiting bone tissue growth. By incorporating catechol groups and disulfide bonds into polyurethane (PU) molecules, an injectable and porous PU adhesive is developed with both superior wet adhesion and biodegradability to facilitate the reduction and fixation of comminuted fractures and the subsequent regeneration of bone tissue. The bone adhesive can be cured within a reasonable time acceptable to a surgeon, and then the wet bone adhesive strength is near 1.30 MPa in 1 h. Finally, the wet adhesive strength to the cortical bone will achieve about 1.70 MPa, which is also five times more than nonresorbable poly(methyl methacrylate) bone cement. Besides, the cell culture experiments also indicate that the adhesives show excellent biocompatibility and osteogenic ability in vitro. Especially, it can degrade in vivo gradually and promote fracture healing in the rabbit iliac fracture model. These results demonstrate that this ingenious bone adhesive exhibits great potential in the treatment of comminuted fractures, providing fresh insights into the development of clinically applicable bone adhesives.

Mechanically Reinforced and Injectable Universal Adhesive Based on a PEI-PAA/Alg Dual-Network Hydrogel Designed by Topological Entanglement and Catechol Chemistry.

Universal adhesion of hydrogels to diverse materials is essential to their extensive applications. Unfortunately, tough adhesion of wet surfaces remains an urgent challenge so far, requiring robust cohesion strength for effective stress dissipation. In this work, a dual-network hydrogel polyethylenimine-poly(acrylic acid)/alginate (PEI-PAA/Alg) with excellent mechanical strength is realized via PEI-PAA complex and calcium alginate coordination for universal adhesion by the synergistic effort of topological entanglement and catechol chemistry. The dual networks of PEI-PAA/Alg provide mechanically reinforced cohesion strength, which is sufficient for energy dissipation during adhesion with universal materials. After the integration of mussel-inspired dopamine into PAA or Alg, the adhesive demonstrates further improved adhesion performance with a solid adherend and capability to bond cancellous bones. Notably, the dopamine-modified adhesive exhibits better instant adhesion and reversibility with wet surfaces compared with commercial fibrin. Adhesion interfaces are investigated by SEM and micro-FTIR to verify the effectiveness of strategies of topological entanglement. Furthermore, the adhesive also possesses great injectability, stability, tissue adhesion, and biocompatibility. In vivo wound healing and histological analysis indicate that the hydrogel can promote wound closure, epidermis regeneration, and tissue refunctionalization, implying its potential application for bioadhesive and wound dressing.

Elevated Thyroglobulin Antibody Level is Associated with Decreased Anti-Müllerian Hormone in Women of Reproductive Age.

Purpose: Women with Hashimoto's thyroiditis (HT) have an increased risk of ovarian insufficiency. However, whether thyroid antibodies affect the ovarian reserve remains controversial. The aim of this study was to explore the possible relationship between anti-Müllerian hormone (AMH) and thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels in women of reproductive age. Methods: A total of 483 women between 18 and 45 years old who had their TPOAb, TgAb, thyroid-stimulating hormone (TSH), free thyroxine (FT4), and AMH levels measured on the same day were enrolled in this study. The levels of TSH, FT4, TPOAb, and TgAb, the prevalence of overt and subclinical hypothyroidism, and the positive rate of TPOAb and TgAb were compared between patients with low (below the 10th percentile), normal (10th to 90th percentile), and high (higher than the 90th percentile) AMH levels. Results: The median AMH level was 1.72 (0.33-4.27) ng/mL. A total of 9.9% of patients had low AMH levels. The TgAb levels and the prevalence of TgAb positivity were higher in the low AMH group (37.62 (13.10-232.68) IU/mL, 35.42%) than in the normal (12.46 (10.0-67.04) IU/mL, 19.59%) and high (13.61 (10.0-95.74) IU/mL, 23.4%) AMH groups (p=0.001, p=0.040, respectively). Serum AMH levels were inversely correlated with TgAb levels (r = -0.114, p=0.013). Conclusion: The AMH of women of reproductive age is affected by HT. Furthermore, women with the lowest AMH level had higher levels of TgAb and a positive rate of TgAb, and high TgAb levels may cause autoimmune damage to the ovaries.

Effects of cadmium on liver function in turtle Mauremys reevesii.

This research was designed to investigate the effects of cadmium (Cd) on liver function in turtle Mauremys reevesii. Turtles were divided into 4 groups at random. The turtles were injected intraperitoneally with Cd at 0, 7.5, 15, 30 mg kg-1 Cd chloride separately. Liver index was calculated. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and the content of TP in liver were examined with biochemical methods. The results indicated that the liver index of turtles changed obviously only at higher dose and longer time. The activities of ALT and AST in liver increased with prolongation of exposure time in a dose-dependent manner. TP content in liver was lower than that in the control. In summary, Cd had an obvious toxic effect on liver tissues of freshwater turtle Mauremys reevesii, and it was dose dependent with the extension of exposure time. But the results also showed that the turtle had strong tolerance to Cd.

Effects of Aromatherapy Massage Combined with TCM Emotional Release Technique on Maternal and Neonatal Physical and Mental Health and Family Relationship in Patients with Postpartum Depression.

Objective: To explore the effects of aromatherapy massage combined with TCM emotional release technique on maternal and neonatal physical and mental health and family relationships in patients with postpartum depression. Methods: A The total number of participants in the study was 160, who were evenly distributed through random assignment into four groups of 40 in each group. This random assignment process was designed to ensure that each group was similar in terms of demographic characteristics and other potential confounding factors to increase the comparability and internal validity of the study. The 160 patients with postpartum depression admitted to the obstetrics department of the Hebei 3a Hospital were enrolled between April 2021 and May 2022, and they were randomly divided into control group, sweet orange aromatherapy massage group, emotional release technique group and combination group, 40 cases in each group. The negative emotions, stress state, mania, levels of neurotransmitters and family intimacy adaptability were compared in the four groups before and after intervention. Results: After the intervention, scores of a generalized anxiety disorder (GAD-7) and Edinburgh Postpartum Depression Scale (EPDS) in the combination group were higher than those in the other three groups, and were higher in the emotional release technique group and sweet orange aromatherapy massage group than control group (P < .05). After the intervention, scores of PTSD Checklist-Civilian Version (PCL) and 32-item hypomania checklist (HCL-32) were the highest in the control group, followed by the sweet orange aromatherapy massage group, emotional release technique group and combination group (P < .05). After the intervention, levels of 5-hydroxytryptamine (5-HT) and dopamine (DA) were the highest in the combination group, followed by the emotional release technique group, sweet orange aromatherapy massage group, and control group (P < .05), and adaptability level of family intimacy was also in the same order (P < .05). In the combined treatment group, generalized anxiety disorder score (GAD-7) and postpartum depression scale (EPDS) scores were increased compared with the control group, indicating increased symptom severity in these two areas. GAD-7 and EPDS scores also increased significantly in the emotional release technique group and the sweet orange aromatherapy massage group. Although the magnitude of the increase may be different, both interventions seemed to lead to an increase in anxiety and depressive symptoms. As the intervention progressed, the control group had the highest scores on the Post-Traumatic Stress Disorder Checklist-Citizen Version (PCL) and the Hyperactivity Checklist 32 (HCL-32), followed by the Sweet Orange Aromatherapy Massage Group and the Emotional Release Technique group and combined treatment group. This indicates that symptom severity was significantly higher in the control group than in the other intervention groups in both areas. Levels of serotonin (5-HT) and dopamine (DA) increased in different groups, the highest in the combined treatment group, followed by the emotional release technique group, sweet orange aromatherapy massage group and the control group. This may indicate that the combination treatment had a positive effect on modulating the levels of these neurotransmitters. The adaptation level of family intimacy also changed according to the same trend. The highest level was in the combined treatment group, followed by the emotional release technique group, the sweet orange aromatherapy massage group and the control group. This may mean that combined treatment has a positive impact on the adaptability of family relationships. Conclusion: Aromatherapy massage combined with an emotional release technique can reduce negative emotions, stress, and mania, improve positive emotions and family intimacy adaptability of patients. These findings have important clinical implications as they relate to the well-being of women and families in the postpartum period. Reducing negative emotions and stress will improve women's mental health and improve their quality of life. In addition, positive emotional support helps create a healthy family atmosphere and has a positive impact on society as a whole.