Amphiregulin secreted by umbilical cord Multipotent Stromal Cells protects against ferroptosis of macrophages via the Activating Transcription Factor 3-CD36 axis to alleviate endometrial fibrosis.

Endometrium fibrosis is the leading cause of uterine infertility. Macrophages participated in the occurrence and development of endometrial fibrosis. We previously reported that human umbilical cord multipotent stromal cells (hUC-MSCs) exerted their therapeutic effect in a macrophage-dependent manner in endometrial fibrosis. However precise mechanisms by which hUC-MSCs may influence macrophages in endometrial fibrosis remain largely unexplored. Here, we demonstrated that abnormal iron and lipid metabolism occurred in intrauterine adhesions (IUA) patients and murine models. Ferroptosis has been proven to contribute to the progression of fibrotic diseases. Our results revealed that pharmacological activation of ferroptosis by Erastin aggravated endometrial fibrosis, while inhibition of ferroptosis by Ferrostatin-1 ameliorated endometrial fibrosis in vivo. Moreover, ferroptosis of macrophages was significantly upregulated in endometria of IUA murine models. Of note, transcriptome profiles revealed that CD36 gene expression was significantly increased in IUA patients and immunofluorescence analysis showed CD36 protein was mainly located in macrophages. Silencing CD36 in macrophages could reverse cell ferroptosis. Dual luciferase reporter assay revealed that CD36 was the direct target of activation transcription factor 3 (ATF3). Furthermore, through establishing coculture system and IUA murine models, we found that hUC-MSCs had a protective role against macrophage ferroptosis and alleviated endometrial fibrosis related to decreased CD36 and ATF3. The effect of hUC-MSCs on macrophage ferroptosis was attributed to the upregulation of amphiregulin (AREG). Our data highlighted that macrophage ferroptosis occurred in endometrial fibrosis via the ATF3-CD36 pathway and hUC-MSCs protected against macrophage ferroptosis to alleviate endometrial fibrosis via secreting AREG. These findings provided a potential target for therapeutic implications of endometrial fibrosis.

Molecular Recognition with Macrocyclic Receptors for Application in Precision Medicine.

ConspectusMacrocyclic receptors can serve as alternatives to natural recognition systems as recognition tools. They provide effectively preorganized cavities to encapsulate guests via host-guest interactions, thereby affecting the physiochemical properties of the guests. Macrocyclic receptors exhibit chemical and thermal stabilities higher than those of natural receptors and thus are expected to resist degradation inside the body. This reduces the risk of harmful degradation byproducts and ensures optimal levels of effectiveness. Macrocyclic receptors have precise molecular weights and well-defined structures; this ensures their batch-to-batch reproducibility, which is critical for ensuring quality and effectiveness levels. Moreover, macrocyclic receptors exhibit broad modification tunabilities, rendering them adaptable to various guests. Molecular recognition is the basis of numerous biological processes. Macrocyclic receptors may display considerable potential for application in diagnosing and treating diseases, depending on the host-guest recognition of bioactive molecules. However, the binding affinities and selectivities of macrocyclic receptors toward bioactive molecules are generally insufficient, which may lead to problems such as low diagnosis accuracies, off-target leaking, and interference with normal functions. Therefore, addressing the challenge of the strong and specific complexation of bioactive molecules and macrocyclic receptors is imperative.To overcome this challenge, we proposed the innovative strategies of longitudinal cavity extension and coassembled heteromultivalent recognition for application in the recognition of small molecules and biomacromolecules, respectively. The deepened cavity provides a stronger hydrophobic effect and a larger interaction area while maintaining the framework rigidity. By coassembling two macrocyclic amphiphiles into one ensemble, we achieved the desired heteromultivalent recognition. This strategy affords the necessary binding properties while preventing the requirement of tedious steps and site mismatch in covalent synthesis. Using these two strategies, we achieved specific and strong binding of macrocyclic receptors to various bioactive molecules including biomarkers, drugs, and disease-related peptides/proteins. We then applied these macrocyclic receptor-based recognition systems in biosensing and bioimaging, drug delivery, and therapeutics.In this Account, we summarize the strategies we used in the recognition of small molecules and biomacromolecules. Thereafter, we discuss their applications in precision medicine, involving the (1) sensing of biomarkers and imaging of lesion sites, which are critical in the early screening of diseases and accurate diagnoses; (2) precise loading and targeted delivery of drugs, which are crucial in improving their therapeutic efficacies and reducing their side effects; and (3) capture and removal of disease-related biomacromolecules, which are significant for precise intervention in life processes. Finally, we propose recommendations for the further development of macrocyclic receptor-based recognition systems in biomedicine. Macrocyclic receptors exhibit considerable potential for research, and continued investigation may not only expand the applications of supramolecular chemistry but also open novel avenues for the development of precision medicine.

Real-time imaging reveal anisotropic dissolution behaviors of silver nanorods.

The morphology and size control of anisotropic nanocrystals are critical for tuning shape-dependent physicochemical properties. Although the anisotropic dissolution process is considered to be an effective means to precisely control the size and morphology of nanocrystals, the anisotropic dissolution mechanism remains poorly understood. Here, usingin situliquid cell transmission electron microscopy, we investigate the anisotropic etching dissolution behaviors of polyvinylpyrrolidone (PVP)-stabilized Ag nanorods in NaCl solution. Results show that etching dissolution occurs only in the longitudinal direction of the nanorod at low chloride concentration (0.2 mM), whereas at high chloride concentration (1 M), the lateral and longitudinal directions of the nanorods are dissolved. First-principles calculations demonstrate that PVP is selectively adsorbed on the {100} crystal plane of silver nanorods, making the tips of nanorods the only reaction sites in the anisotropic etching process. When the chemical potential difference of the Cl-concentration is higher than the diffusion barrier (0.196 eV) of Cl-in the PVP molecule, Cl-penetrates the PVP molecular layer of {100} facets on the side of the Ag nanorods. These findings provide an in-depth insight into the anisotropic etching mechanisms and lay foundations for the controlled preparation and rational design of nanostructures.

Synthesis and anti-proliferative effect of novel 4-Aryl-1, 3-Thiazole-TPP conjugates via mitochondrial uncoupling process.

With the advent of mitochondrial targeting moiety such as triphenlyphosphonium cation (TPP+), targeting mitochondria in cancer cells has become a promising strategy for combating tumors. Herein, a series of novel 4-aryl-1,3-thiazole derivatives linked to TPP+ moiety were designed and synthesized. The cytotoxicity against a panel of four cancer cell lines was evaluated by CCK-8 assay. Most of these compounds exhibited moderate to good inhibitory activity over HeLa, PC-3 and HCT-15 cells while MCF-7 cells were less sensitive to most compounds. Among them, compound 12a exhibited a significant anti-proliferative activity against HeLa cells, and prompted for further investigation. Specifically, 12a decreased mitochondrial membrane potential and enhanced levels of reactive oxygen species (ROS). The flow cytometry analysis revealed that compound 12a could induce apoptosis and cell cycle arrest at G0/G1 phase in HeLa cells. In addition, mitochondrial bioenergetics assay revealed that 12a displayed mild mitochondrial uncoupling effect. Taken together, these findings suggest the therapeutic potential of compound 12a as an antitumor agent targeting mitochondria.

Calixarene-Based Supramolecular Sensor Array for Pesticide Discrimination.

The identification and detection of pesticides is crucial to protecting both the environment and human health. However, it can be challenging to conveniently and rapidly differentiate between different types of pesticides. We developed a supramolecular fluorescent sensor array, in which calixarenes with broad-spectrum encapsulation capacity served as recognition receptors. The sensor array exhibits distinct fluorescence change patterns for seven tested pesticides, encompassing herbicides, insecticides, and fungicides. With a reaction time of just three minutes, the sensor array proves to be a rapid and efficient tool for the discrimination of pesticides. Furthermore, this supramolecular sensing approach can be easily extended to enable real-time and on-site visual detection of varying concentrations of imazalil using a smartphone with a color scanning application. This work not only provides a simple and effective method for pesticide identification and quantification, but also offers a versatile and advantageous platform for the recognition of other analytes in relevant fields.

Radiologic, clinical, and functional evaluation of children with displaced T-condylar fractures treated by closed reduction and percutaneous fixation using the Mayo Elbow Performance Score.

PURPOSE: T-condylar (T-C) fractures of the distal humerus are rare in children. There is no accepted treatment for such an injury, and there is a lack of reports evaluating the outcome of T-C fractures treated by closed reduction and percutaneous fixation. The aim of this study was to evaluate the feasibility of closed reduction and percutaneous K-wire and screw (CRPKS) fixation in patients with type II and III T-C fractures according to the Toniolo-Wilkins classification modified by Canavese et al. (TWC classification). METHODS: The clinical data of 12 consecutive patients (8 males, 4 females) who were younger than 14 years of age and who had a T-C fracture that was managed by CRPKS were retrospectively evaluated. Fractures were classified according to the TWC classification. The baseline information of the patients, carrying angle (CA) and Mayo Elbow Performance Score (MEPS) were used to evaluate clinical and functional outcomes; related complications were recorded. Statistical analysis was performed. RESULTS: The mean age at the time of injury was 11.6 ± 1.8 years (range, 8-14). The time from injury to surgical treatment was 1.5 ± 1.0 days (range, 0-3), and the mean follow-up duration was 33.7 ± 12.3 months (range, 18-61). Surgery lasted 45.7 ± 7.6 min on average (range, 35-58). All fractures healed in 4.9 ± 1.0 weeks on average (range, 4-7). At the last follow-up visit, the CA was 12.6° ± 5.8° on the injured side and 13.8° ± 1.8° on the uninjured side (p=0.432). The MEPS was 100 (95, 100) on the injured side and 100 (100, 100) on the uninjured side (p=0.194). Three complications were recorded. CONCLUSION: Good functional and radiological outcomes can be expected in pediatric patients with type II and III T-C fractures treated by CRPKS. The technique is relatively simple to perform and has a lower rate of complications.

Association of Nirmatrelvir/Ritonavir Treatment on Upper Respiratory Severe Acute Respiratory Syndrome Coronavirus 2 Reverse Transcription-Polymerase Chain Reaction (SARS-Cov-2 RT-PCR) Negative Conversion Rates Among High-Risk Patients With Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Acceleration of negative respiratory conversion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19) might reduce viral transmission. Nirmatrelvir/ritonavir is a new antiviral agent recently approved for treatment of COVID-19 that has the potential to facilitate negative conversion. METHODS: A cohort of hospitalized adult patients with mild-to-moderate COVID-19 who had a high risk for progression to severe disease were studied. These patients presented with COVID-19 symptoms between 5 March and 5 April 2022. The time from positive to negative upper respiratory reverse transcription-polymerase chain reaction (RT-PCR) conversion was assessed by Kaplan-Meier plots and Cox proportional hazards regression with the adjustment for patients' baseline demographic and clinical characteristics. RESULTS: There were 258 patients treated with nirmatrelvir/ritonavir and 224 nontreated patients who had mild-to-moderate COVID-19. The median (interquartile range) time for patients who converted from positive to negative RT-PCR was 10 days (7-12 days) in patients treated ≤5 days after symptom onset and 17 days (12-21 days) in nontreated patients. The proportions of patients with a negative conversion at day 15 were 89.7% and 42.0% in treated patients and nontreated patients, corresponding to a hazard ratio of 4.33 (95% confidence interval, 3.31-5.65). Adjustment for baseline differences between the groups had little effect on the association. Subgroup analysis on treated patients suggests that time to negative conversion did not vary with the patients' baseline characteristics. CONCLUSIONS: This cohort study of high-risk patients with mild-to-moderate COVID-19 found an association between nirmatrelvir/ritonavir treatment and accelerated negative RT-PCR respiratory SARS-CoV-2 conversion that might reduce the risk of viral shedding and disease transmission.

Risk-stratified approach by aMAP score for community population infected with hepatitis B and C to guide subsequent liver cancer screening practice: A cohort study with 10-year follow-up.

The aim of this study was to determine whether the age-Male-ALBI-Platelet (aMAP) score is applicable in community settings and how to maximise its role in risk stratification. A total of thousand five hundred and three participants had an aMAP score calculated at baseline and were followed up for about 10 years to obtain information on liver cancer incidence and death. After assessing the ability of aMAP to predict liver cancer incidence and death in terms of differentiation and calibration, the optimal risk stratification threshold of the aMAP score was explored, based on absolute and relative risks. The aMAP score achieved higher area under curves (AUCs) (almost all above 0.8) within 10 years and exhibited a better calibration within 5 years. Regarding absolute risk, the risk of incidence of and death from liver cancer showed a rapid increase after an aMAP score of 55. The cumulative incidence (5-year: 8.3% vs. 1.3% and 10-year: 20.9% vs. 3.6%) and mortality (5-year: 6.7% vs. 1.1% and 10-year: 17.5% vs. 3.1%) of liver cancer in individuals with an aMAP score of ≥55 were significantly higher than in those with a score of <55 (Grey's test p < .001). In terms of relative risk, the risk of death from liver cancer surpassed that from other causes after an aMAP score of ≥55 [HR = 1.38(1.02-1.87)]. Notably, the two types of death risk had opposite trends between the subpopulation with an aMAP score of ≥55 and < 55. To conclude, this study showed the value of the aMAP score in community settings and recommends using 55 as a new risk stratification threshold to guide subsequent liver cancer screening.

Ultraviolet communication with a large scattering angle via artificial agglomerate fog.

Considering strong signal attenuation of the large-angle non-line-of-sight (NLOS) link achieved due to the ultraviolet (UV) scattering properties, we propose to increase the UV communication link gain under a large scattering angle via generating agglomerate fog within a certain range as a secondary light source. In this study, a channel model with locally strong scatterers from agglomerate fog is proposed based on Monte Carlo ray-tracing approaches. Mie theory is adopted to calculate the atmospheric channel parameters, to further evaluate the link gain of a channel under non-uniform atmosphere. The performance of scattering system in the presence of fog conditions depends on the relative positions of the light source to the fog and to the receiver. The link gain results reveal the transmission capabilities for different scattering channel geometries, and give the optimal spray point location within a 10 m communication range. We further establish a foggy NLOS system using an agglomerate fog generator to verify our research in the real environment. The results show that the received signal strength of the NLOS link can be effectively enhanced by constructing scatterers in the atmospheric channel, which significantly decreases the bit-error rate (BER).

Melatonin-Primed MSCs Alleviate Intrauterine Adhesions by Affecting MSC-Expressed Galectin-3 on Macrophage Polarization.

Intrauterine adhesion (IUA) is characterized by the presence of fibrosis in the uterine cavity. It is mainly caused by infection or trauma to the endometrium, and it imposes a great challenge to female reproductive health. Mesenchymal stem cells (MSCs) have been used to regenerate the human endometrium in patients with IUA, but stem cell therapy is not curative in some patients. Melatonin (MT) was reported as a potential modulator of MSCs. However, it remains unclear whether MSCs pretreated with MT exert an improved therapeutic effect on IUA. In this study, an IUA model was established using our invented electric scratching tool. Our results illustrated that MT-pretreated MSCs significantly attenuated the development of IUA. Moreover, MT-pretreated MSCs highly expressed galectin-3 (Gal-3), which enhanced MSC proliferation and migration and influenced macrophage polarization. Of note, IUA mice exhibited colonic injury, and MT-pretreated MSCs alleviated this injury by normalizing colonic microbial communities and recruiting macrophages. Furthermore, inhibition of sympathetic nerves had no effect on IUA progression but delayed colonic injury, and Gal-3 combined with norepinephrine better promoted M2-like macrophage polarization and inhibited M1-like macrophage polarization. Together, these data indicated that MT-primed MSCs can ameliorate injury of both the uterus and colon in an IUA model through high Gal-3 expression to influence sympathetic nerves and in turn affect the polarization and recruitment of macrophages.

Production of Tone 2 in disyllabic words in Mandarin Chinese speaking children aged 3-5 with a cochlear implant and a contralateral hearing aid.

To investigate Mandarin Tone 2 production of disyllabic words of prelingually deafened children with a cochlear implant (CI) and a contralateral hearing aid (HA) and to evaluate the relationship between their demographic variables and tone-production ability. Thirty prelingually Mandarin-speaking preschoolers with CI+HA and 30 age-matched normal-hearing (NH) children participated in the study. Fourteen disyllabic words were recorded from each child. A total of 840 tokens (14 × 60) were then used in tone-perception tests in which four speech therapists participated. The production of T2-related disyllabic words of the bimodal group was significantly worse than that of the NH group, as reflected in the overall accuracy (88.57% ± 16.31% vs 99.29% ± 21.79%, p < 0.05), the accuracy of T1+T2 (93.33% vs 100%), the accuracy of T2+T1 (66.67 ± 37.91% vs 98.33 ± 9.13%), and the accuracy of T2+T4 (78.33 ± 33.95% vs 100%). In addition, the bimodal group showed significantly inferior production accuracy of T2+T1 than T2+T2 and T3+T2, p < 0.05. Both bimodal age and implantation age were significantly negatively correlated with the overall production accuracy, p < 0.05. For the error patterns, bimodal participants experienced more errors when T2 was in the first position of the tone combination, and T2 was most likely to be mispronounced as T1 and T3. Bimodal patients aged 3-5 have T2-related disyllabic lexical tone production defects, and their performances are related to tone combination, implantation age, and bimodal age.

Interleukin-34 accelerates intrauterine adhesions progress related to CX3CR1+ monocytes/macrophages.

Intrauterine adhesions (IUA) are characterized by endometrial fibrosis and impose a great challenge for female reproduction. IL-34 is profoundly involved in various fibrotic diseases through regulating the survival, proliferation, and differentiation of monocytes/macrophages. However, it remains unclear how IL-34 regulates monocytes/macrophages in context of IUA. Here, we showed that the expression level of IL-34 and the amount of CX3CR1+ monocytes/macrophages were significantly increased in endometrial tissues of IUA patients. IL-34 promoted the differentiation of monocytes/macrophages, which express CX3CR1 via CSF-1R/P13K/Akt pathway in vitro. Moreover, IL-34-induced CX3CR1+ monocytes/macrophages promoted the differentiation of endometrial stromal cells into myofibroblasts. Of note, IL-34 caused endometrial fibrosis and increased the amount of CX3CR1+ monocytes/macrophages in endometrial tissues in vivo. IL-34 modulated endometrial fibrosis by regulating monocytes/macrophages since the elimination of endometrial monocytes/macrophages significantly suppressed the profibrotic function of IL-34. Finally, blocking of IL-34 in the LPS-IUA model resulted in the improvement of endometrial fibrosis and decreased number of CX3CR1+ monocytes/macrophages. Our studies uncover the novel mechanism of interaction between IL-34-induced CX3CR1+ monocytes/macrophages and endometrial stromal cells in endometrial fibrosis pathogenesis, and highlight IL-34 as a critical target for treating IUA.

A Calixarene Assembly Strategy of Combined Anti-Neuroinflammation and Drug Delivery Functions for Traumatic Brain Injury Therapy.

Excessive inflammatory reaction aggravates brain injury and hinders the recovery of neural function in nervous system diseases. Microglia, as the major players of neuroinflammation, control the progress of the disease. There is an urgent need for effective non-invasive therapy to treat neuroinflammation mediated by microglia. However, the lack of specificity of anti-inflammatory agents and insufficient drug dose penetrating into the brain lesion area are the main problems. Here, we evaluated a series of calixarenes and found that among them the self-assembling architecture of amphiphilic sulfonatocalix[8]arene (SC8A12C) had the most potent ability to suppress neuroinflammation in vitro and in vivo. Moreover, SC8A12C assemblies were internalized into microglia through macropinocytosis. In addition, after applying the SC8A12C assemblies to the exposed brain tissue, we observed that SC8A12C assemblies penetrated into the brain parenchyma and eliminated the inflammatory factor storm, thereby restoring neurobiological functions in a mouse model of traumatic brain injury.

Response to 'Cesarean section or non-breastfeeding for prevention of MTCT - Beware of sending the wrong message'.

We are glad to respond to the concerns of Drs. Levy and Terrault about our articles on the mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in HBeAg-positive mothers. We agree with Drs. Levy and Terrault that antiviral therapy of HBV during pregnancy could effectively decrease the MTCT, and this strategy has been recommended by WHO for pregnant women with a high viral load. However, the long-term influences of the abrupt cessation of antiretroviral drugs in mothers and prenatal exposure to antiviral drugs in newborns are not completely understood and are still under investigation. And not all pregnant mothers would accept this regiment due to the medication availability and individual willingness. It makes sense to study the influential factors on MTCT among mothers with high-risk transmission but not taking antiviral drugs. Despite the relatively large number of subjects included in our cohort (N = 857), post hoc power computation shows that the test efficacy is far from adequate to detect the association between delivery mode or feeding type and HBV MTCT. Therefore, we summarized the relevant studies to reach a relatively reasonable conclusion in HBsAg- and HBeAg-positive pregnant mothers not taking antiviral drugs. We provide an alternative option for HBsAg- and HBeAg-positive pregnant mothers who cannot access or defer to antiviral therapy during pregnancy to reduce the risk of HBV transmission to their offspring.

Positive Regulatory Domain I-binding Factor 1 Mediates Peripheral Nerve Injury-induced Nociception in Mice by Repressing Kv4.3 Channel Expression.

BACKGROUND: The transcriptional repressor positive regulatory domain I-binding factor 1 (PRDM1) is expressed in adult mouse dorsal root ganglion and regulates the formation and function of peripheral sensory neurons. The authors hypothesized that PRDM1 in the dorsal root ganglion may contribute to peripheral nerve injury-induced nociception regulation and that its mechanism may involve Kv4.3 channel transcriptional repression. METHODS: Nociception was induced in C57BL/6 mice by applying chronic constriction injury, complete Freund's adjuvant, or capsaicin plantar injection. Nociceptive response was evaluated by mechanical allodynia, thermal hyperalgesia, cold hyperalgesia, or gait analysis. The role of PRDM1 was evaluated by injection of Prdm1 knockdown and overexpression adeno-associated viruses. The interaction of PRDM1 at the Kv4.3 (Kcnd3) promoter was evaluated by chromatin immunoprecipitation assay. Excitability of dorsal root ganglion neurons was evaluated by whole cell patch clamp recordings, and calcium signaling in spinal dorsal horn neurons was evaluated by in vivo two-photon imaging. RESULTS: Peripheral nerve injury increased PRDM1 expression in the dorsal root ganglion, which reduced the activity of the Kv4.3 promoter and repressed Kv4.3 channel expression (injured vs. uninjured; all P < 0.001). Knockdown of PRDM1 rescued Kv4.3 expression, reduced the high excitability of injured dorsal root ganglion neurons, and alleviated peripheral nerve injury-induced nociception (short hairpin RNA vs. Scram; all P < 0.05). In contrast, PRDM1 overexpression in naive mouse dorsal root ganglion neurons diminished Kv4.3 channel expression and induced hyperalgesia (PRDM1 overexpression vs. control, mean ± SD; n = 13; all P < 0.0001) as evaluated by mechanical allodynia (0.6 ± 0.3 vs. 1.2 ± 0.2 g), thermal hyperalgesia (5.2 ± 1.3 vs. 9.8 ± 1.7 s), and cold hyperalgesia (3.4 ± 0.5 vs. 5.3 ± 0.6 s). Finally, PRDM1 downregulation in naive mice reduced the calcium signaling response of spinal dorsal horn neurons to thermal stimulation. CONCLUSIONS: PRDM1 contributes to peripheral nerve injury-induced nociception by repressing Kv4.3 channel expression in injured dorsal root ganglion neurons.

Ferumoxytol-ß-glucan Inhibits Melanoma Growth via Interacting with Dectin-1 to Polarize Macrophages into M1 Phenotype.

Background: Regulating the polarization of macrophages to antitumor M1 macrophages is a promising strategy for overcoming the immunosuppression of the tumor microenvironment for cancer therapy. Ferumoxytol (FMT) can not only serve as a drug deliver agent but also exerts anti-tumor activity. ß-glucan has immuno-modulating properties to prevent tumor growth. Thus, a nanocomposite of FMT surface-coated with ß-glucan (FMT-ß-glucan) was prepared to explore its effect on tumor suppression. Methods: Male B16F10 melanoma mouse model was established to explore the antitumor effect of FMT-ß-glucan. The viability and apoptotic rates of B16F10 cells were detected by cell counting kit-8 and Annexin-V/PI experiments. The levels of M1 markers were quantified by quantitative reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay. Phagocytic activity and intracellular reactive oxygen species (ROS) in macrophages were evaluated by the neutral red uptake assay and flow cytometry, respectively. Small interfering RNA (siRNA) transfection was applied to knock down the Dectin-1 gene in RAW 264.7 cells. Results: FMT-ß-glucan suppressed tumor growth to a greater extent and induced higher infiltration of M1 macrophages than the combination of FMT and ß-glucan (FMT+ß-glucan) in vivo. In vitro, supernatant from FMT-ß-glucan-treated RAW 264.7 cells led to lower cell viability and induced more apoptosis of B16F10 cells than that from the FMT+ß-glucan group. Moreover, FMT-ß-glucan boosted the expression of M1 type markers, and increased phagocytic activity and ROS in RAW 264.7 cells. Further research indicated that FMT-ß-glucan treatment promoted the level of Dectin-1 on the surface of RAW 264.7 cells and that knockdown of Dectin-1 abrogated the phosphorylation levels of several components in MAPK and NF-κB signaling. Conclusion: The nanocomposite FMT-ß-glucan suppressed melanoma growth by inducing the M1 macrophage-activated tumor microenvironment.

Biomedical Applications of Calixarenes: State of the Art and Perspectives.

Calixarenes (CAs), representing the third generation of supramolecular hosts and one of the most widely studied macrocyclic scaffolds, offer (almost) unlimited structure and application possibilities due to their ease of modification, which allows one to establish a large molecular library as a material basis for diverse biomedical applications. Moreover, CAs and their derivatives engage in various noncovalent interactions for the facile recognition of guests including bioactive molecules and are also important building blocks for the fabrication of supramolecular architectures. In view of their molecular recognition and self-assembly properties, CAs are extensively applied in biosensing, bioimaging, and drug/gene delivery. Additionally, some CA derivatives exhibit biological activities and can therefore be used as new therapeutic agents. Herein, we summarize the diverse biomedical applications of CAs including in vitro diagnosis (biosensing), in vivo diagnosis (bioimaging), and therapy.

An Amphiphilic Sulfonatocalix[5]arene as an Activator for Membrane Transport of Lysine-rich Peptides and Proteins.

Lysine (K) is an important target residue for protein and peptide delivery across membranes. K is the most frequently exposed residue in proteins, leading to high demand for the development of K-compatible transport activators. However, designing activators for K-rich peptides and proteins is more challenging than for arginine-rich species because of the kosmotropic nature of K and its recognition difficulty. In this study, we designed a new amphiphilic sulfonatocalix[5]arene (sCx5-6C) as a K-compatible transport activator. sCx5-6C was tailored with two key elements, recognition of K and the ability to embed into membranes. We measured the membrane transport efficiencies of α-poly-l-lysine, heptalysine, and histones across artificial membranes and of α-poly-l-lysine into live cells, activated by sCx5-6C. The results demonstrate that sCx5-6C acts as an efficient activator for translocating K-rich peptides and proteins, which cannot be achieved by known arginine-compatible activators.

The impact of N-cadherin-ß-catenin signaling on the analgesic effects of glial cell-derived neurotrophic factor in neuropathic pain.

Long-term neuropathic pain can lead to anxiety, depression, and other issues, which seriously affect patients' quality of life. For this reason, it is important to find effective treatments. Studies have shown that glial cell-derived neurotrophic factor (GDNF) can relieve neuropathic pain. However, its mechanism of action is unknown. Our previous study of GDNF suggested that the N-cadherin-ß-catenin transmembrane signaling system might play a role in GDNF transmembrane signaling. Based on this, the current study aimed to produce a neuropathic pain model to confirm the activation of the N-cadherin-ß-catenin signaling system in the spinal dorsal horn under pain conditions and to study the impact of GDNF intrathecal injection on central sensitization of dorsal horn neurons. The results showed that N-cadherin expression, as well as the expression of membrane-associated ß-catenin, was reduced in the dorsal horn of the spinal cord in the chronic pain model. Intrathecal injection of GDNF could reactivate the N-cadherin-ß-catenin system, improve central sensitization, and relieve pain. Knockdown of N-cadherin or ß-catenin could significantly reduce the analgesic effect of GDNF. These results provide clear experimental evidence that the N-cadherin-ß-catenin signaling system participates in the analgesic effect of GDNF in neuropathic pain and help identify transmembrane and intracellular signal transduction mechanisms associated with GDNF's analgesic effects.

The role of caesarean section and nonbreastfeeding in preventing mother-to-child transmission of hepatitis B virus in HBsAg-and HBeAg-positive mothers: results from a prospective cohort study and a meta-analysis.

The study aimed to assess whether caesarean section and nonbreastfeeding can prevent mother-to-child transmission (MTCT) in HBsAg- and HBeAg-positive mothers via a cohort study and a meta-analysis. (1) Pregnant women who were positive for HBsAg and HBeAg and did not receive antiviral treatment during pregnancy were recruited from the First Hospital of Jilin University, Maternal and Child Health Care Center of Jiangsu and Henan from August 2009 to June 2015. Infants received active and passive immunity. (2) In addition, a systematic literature search was performed in the PubMed, Embase, Cochrane, China National Knowledge Infrastructure and Wanfang Chinese databases. The retrieval strategy was [("HBV" or "hepatitis b" or "hepatitis b virus") and ("mother-to-infant transmission" or "vertical transmission")]. Studies were screened, and data were extracted. The fixed-effect model was used to analyse the studies. A total of 852 mothers and 857 newborns were enrolled. At the age of 7 months, 41 infants (4.78%) were positive for HBsAg. Multivariate analysis showed that mothers with higher HBV DNA levels (>108  IU/mL; RR = 3.03, 95% CI: 1.41-6.52) were associated with an increased risk of infection. Although there was no statistical significance, caesarean section (RR = 0.61) and nonbreastfeeding (RR = 0.88) showed a tendency to reduce the risk of infection. (2) A total of 5726 studies were identified. Together with our study, 13 were included in the analysis of delivery mode, and 12 were included in the analysis of feeding mode. The risk of infection in the caesarean section group was lower than that in the vaginal delivery group (RR = 0.58, 95% CI: 0.46-0.74). In the analysis of feeding mode, the risk in the nonbreastfeeding group was significantly lower (RR = 0.74, 95% CI: 0.56-0.98). In conclusion, caesarean section and nonbreastfeeding reduced the risk of MTCT in infants of HBsAg- and HBeAg-positive mothers who did not receive antiviral therapy during pregnancy.