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.

Supramolecular 3 in 1: A Lubrication and Co-Delivery System for Synergistic Advanced Osteoarthritis Therapy.

The complexity, heterogeneity, and drug resistance of diseases necessitate a shift in therapeutic paradigms from monotherapy to combination therapy, which could augment treatment efficiency. Effective treatment of advanced osteoarthritis (OA) requires addressing three key factors contributing to its deterioration: chronic joint inflammation, lubrication dysfunction, and cartilage-tissue degradation. Herein, we present a supramolecular nanomedicine of multifunctionality via molecular recognition and self-assembly. The employed macrocyclic carrier, zwitterion-modified cavitand (CV-2), not only accurately loads various drugs but also functions as a therapeutic agent with lubricating properties for the treatment of OA. Kartogenin (KGN), a drug for articular cartilage regeneration and protection, and flurbiprofen (FP), an anti-inflammatory agent, were coloaded onto CV-2 assembly, forming a supramolecular nanomedicine KGN&FP@CV-2. The three-in-one combination therapy of KGN&FP@CV-2 addresses the three pathological features for treating OA collectively, and thus provides long-term therapeutic benefits for OA through sustained drug release and intrinsic lubrication in vivo. The multifunctional integration of macrocyclic delivery and therapeutics provides a simple, flexible, and universal platform for the synergistic treatment of diseases involving multiple drugs.

A case of achalasia associated with early esophageal cancer.

A 65-year-old man was admitted to our hospital complaining of reflux for more than 20 years. After endoscopy and barium-swallow examination, he was diagnosed with achalasia as well as a squamous cell carcinoma. Therefore, peroral endoscopic myotomy (POEM) combined with endoscopic submucosal dissection (ESD) was performed simultaneously. During the procedure, a mucosal erosion with a clear boundary was shown in the middle segment of the esophagus. ESD was first performed and the lesion was removed en-bloc. Subsequent POEM therapy was performed after marking the left esophageal wall 10cm above the cardia. After submucosal injection, the submucosal plane was created through a length 2cm longitudinal incision, then the muscle was cut a length of 10 cm into the esophagus and 2 cm below the cardia, and finally the incision was closed by clips. Pathological examination revealed high-grade intraepithelial neoplasia of squamous epithelium (carcinoma in situ) with a negative margin. The patient was recovered without complication four days after the procedure. The endoscopy showed perfect healing of the esophageal lesions during two-months follow-up , and the reflux symptom was resolved.

Supramolecular Integration of Multifunctional Nanomaterial by Mannose-Decorated Azocalixarene with Ginsenoside Rb1 for Synergistic Therapy of Rheumatoid Arthritis.

The complexity and progressive nature of diseases require the exploitation of multifunctional materials. However, introducing a function inevitably increases the complexity of materials, which complicates preparation and decreases reproducibility. Herein, we report a supramolecular integration of multifunctional nanomaterials based on mannose-modified azocalix[4]arene (ManAC4A) and ginsenoside Rb1 (Rb1), which showed advances of simplicity and reproducibility. ManAC4A possesses reactive oxygen species (ROS) scavenging capacity and hypoxia-responsiveness, together with macrophage-targeting and induction functionality. Collectively, the Rb1@ManAC4A assembly simply prepared by two components is integrated with multifunction, including triple targeting (ELVIS targeting, macrophage-targeting, and hypoxia-targeted release) and triple therapy (ROS scavenging, macrophage polarization, and the anti-inflammatory effect of Rb1). The spontaneous assembly and recognition of ManAC4A, with its precise structure and molecular weight, facilitated the simple and straightforward preparation of Rb1@ManAC4A, leading to excellent batch consistency. Progress in simplicity and reproducibility, as directed by this research, will catalyze the clinical translation of multifunctional materials.

[Effect of moxibustion at "Mingmen" (GV 4) and "Guanyuan" (CV 4) on immune function in healthy rats based on intestinal flora].

OBJECTIVE: To observe the effects of moxibustion at "Mingmen" (GV 4) and "Guanyuan" (CV 4) on immune function and intestinal flora in healthy rats, thereby investigating the underlying mechanism of moxibustion on immune function. METHODS: Twenty 8-week-old SD rats were randomly divided into a young blank group and a young moxibustion group, with 10 rats in each group. Similarly, twenty 8-month-old SD rats were randomly divided into a middle-aged blank group and a middle-aged moxibustion group, with 10 rats in each group. The rats in the two moxibustion groups received moxibustion at "Mingmen" (GV 4) and "Guanyuan" (CV 4), 15 min per session, once daily, five times a week, for a total of four months. The rats in the two blank groups were fed under normal conditions. After the intervention, thymus and spleen indexes were calculated; the morphology of thymus and spleen tissues was observed using HE staining; the flow cytometry was used to detect the expression of CD and CD T lymphocytes and the CD/CD ratio was calculated; ELISA was used to measure the serum levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-17 (IL-17); 16S rRNA high-throughput sequencing was used to analyze the intestinal flora. Additionally, the correlation between the relative abundance of intestinal flora and serum levels of TNF-α, IFN-γ, IL-6, IL-10 and IL-17 was analyzed. RESULTS: Compared with the young blank group, the young moxibustion group exhibited an increase in the cortical area of thymus tissue with tighter lymphocyte arrangement; compared with the middle-aged blank group, the middle-aged moxibustion group showed an increase in thymus index (P<0.05) and an increase in the cortical area of thymus tissue. There were no significant differences in spleen index between the 2 moxibustion groups and the 2 blank groups (P>0.05). There were no significant differences in the expression of CD, CD, and CD/CD ratio between the 2 moxibustion groups and the corresponding blank groups (P>0.05). Compared with the young blank group, the young moxibustion group had elevated IL-6 level (P<0.05); compared with the middle-aged blank group, the middle-aged moxibustion group had decreased IL-10 and IL-17 levels (P<0.05). Compared with the young blank group, the young moxibustion group exhibited increased Sobs index, Ace index, and Chao index (P<0.01, P<0.05), as well as increased relative abundance of Spirochaetota, Treponema, Turicibacter, Rikenellaceae_RC9_gut_group (P<0.05), and decreased relative abundance of Dubosiella (P<0.05). Compared with the middle-aged blank group, the middle-aged moxibustion group had increased relative abundance of Spirochaetota, Treponema, norank_f_Peptococcaceae (P<0.05), and decreased relative abundance of Proteobacteria, Allobaculum, and Faecalibaculum (P<0.05). Correlation analysis revealed that relative abundance of Eubacterium_xylanophilum_group and unclassified _f_Lachnospiraceae was negatively correlated with serum TNF-α level (r=-0.39, P=0.03; r=-0.24, P=0.04), while relative abundance of norank_f_norank_o_Clostridia_UCG-014 and Lactobacillus was positively correlated with serum TNF-α level (r=0.37, P=0.04; r=0.43, P=0.02). The relative abundance of Roseburia and Monoglobus was negatively correlated with serum IFN-γ level (r=-0.40, P=0.02; r=-0.44, P=0.01), while relative abundance of Lactobacillus was positively correlated with serum IL-10 level (r=0.43, P=0.02). CONCLUSION: Moxibustion could improve immune function in healthy rats, and its mechanism may be related to the regulation of relative abundance of intestinal flora.

Dual hypoxia-responsive supramolecular complex for cancer target therapy.

The prognosis with pancreatic cancer is among the poorest of any human cancer. One of the important factors is the tumor hypoxia. Targeting tumor hypoxia is considered a desirable therapeutic option. However, it has not been translated into clinical success in the treatment of pancreatic cancer. With enhanced cytotoxicities against hypoxic pancreatic cancer cells, BE-43547A2 (BE) may serve as a promising template for hypoxia target strategy. Here, based on rational modification, a BE prodrug (NMP-BE) is encapsulated into sulfonated azocalix[5]arene (SAC5A) to generate a supramolecular dual hypoxia-responsive complex NMP-BE@SAC5A. Benefited from the selective load release within cancer cells, NMP-BE@SAC5A markedly suppresses tumor growth at low dose in pancreatic cancer cells xenograft murine model without developing systemic toxicity. This research presents a strategy for the modification of covalent compounds to achieve efficient delivery within tumors, a horizon for the realization of safe and reinforced hypoxia target therapy using a simple approach.

Retrograde percutaneous coronary intervention of chronic total occlusion via discontinuous septal channels.

OBJECTIVES: The study aims to investigate the safety and feasibility of retrograde CTO intervention via collateral connection grade 0 (CC-0) septal channel and to identify predictors of collateral tracking failure. BACKGROUND: Guidewire crossing a collateral channel is a critical step for successful retrograde percutaneous coronary intervention (PCI) of chronic total occlusion (CTO). METHODS: Retrograde PCI was attempted in 122 cases of CTO with CC-0 septal collaterals from December 2018 to May 2021. A hydrophilic polymer coating guidewire was used for crossing all intended CC-0 collaterals. A multivariable logistic regression analysis was performed to identify the predictors of guidewire tracking failure via the CC-0 collaterals. RESULTS: Successful guidewire tracking via CC-0 septal channel was achieved in 98 (80.3%) of 122 cases. The independent predictors of CC-0 septal channel guidewire tracking failure included well-developed non-septal collateral (OR: 5.297, 95% CI: 1.107-25.353, p = 0.037) and the ratio length of posterior descending artery (PDA) versus the distance of PDA ostium to cardiac apex ≤2/3 (OR: 3.970, 95% CI: 1.454-10.835, p = 0.007). Collateral perforation, target vessel perforation, and cardiac tamponade occurred in 5 (4.1%), 3 (2.5%), and 6 (4.9%) cases, respectively. There were no complications requiring emergency cardiac surgery or revascularization of nontarget vessel. CONCLUSIONS: Retrograde PCI via CC-0 septal channels with a hydrophilic polymer-coated guidewire is feasible and safe in patients with CTO. Well-developed nonseptal collaterals and short PDA length influence the procedure success and the risk of guidewire tracking failure via CC-0 septal channels.

Endoscopic mucosal resection with double band ligation versus endoscopic submucosal dissection for small rectal neuroendocrine tumors.

BACKGROUND: Endoscopic resection remains an effective method for the treatment of small rectal neuroendocrine tumors (NETs) (≤ 10 mm). Moreover, endoscopic mucosal resection (EMR) with double band ligation (EMR-dB), a simplified modification of EMR with band ligation, is an alternative strategy to remove small rectal NETs. AIM: To evaluate the feasibility and safety of EMR-dB for the treatment of small rectal NETs (≤ 10 mm). METHODS: A total of 50 patients with small rectal NETs, without regional lymph node enlargement or distant metastasis confirmed by endoscopic ultrasound, computerized tomography scan, or magnetic resonance imaging, were enrolled in the study from March 2021 to June 2022. These patients were randomly assigned into the EMR-dB (n = 25) group or endoscopic submucosal dissection (ESD) group (n = 25). The characteristics of the patients and tumors, procedure time, devices cost, complete resection rate, complications, and recurrence outcomes were analyzed. RESULTS: There were 25 patients (13 males, 12 females; age range 28-68 years old) in the EMR-dB group, and the ESD group contained 25 patients (15 males, 10 females; age range 25-70 years old). Both groups had similar lesion sizes (EMR-dB 4.53 ± 1.02 mm, ESD 5.140 ± 1.74 mm; P = 0.141) and resected lesion sizes(1.32 ± 0.52 cm vs 1.58 ± 0.84 cm; P = 0.269). Furthermore, the histological complete resection and en bloc resection rates were achieved in all patients (100% for each). In addition, there was no significant difference in the complication rate between the two groups. However, the procedure time was significantly shorter and the devices cost was significantly lower in the EMR-dB group. Besides, there was no recurrence in both groups during the follow-up period. CONCLUSION: The procedure time of EMR-dB was shorter compared with ESD, and both approaches showed a similar curative effect. Taken together, EMR-dB was a feasible and safe option for the treatment of small rectal NETs.

Effect of Frozen-Thawed Embryo Transfer on the Metabolism of Children in Early Childhood.

BACKGROUND: As a routine procedure in assisted reproductive technology (ART), it is crucial to assess the safety of frozen and thawed embryo transfer (FET). We aimed to investigate the metabolic profile of children conceived through FET in their early childhood. METHOD: A total of 147 children between the age of 1.5 and 4 years old, conceived through FET or naturally conceived (NC), were recruited. A total of 89 children, 65 in the FET group and 24 in the NC group (matched with the FET group based on children's BMI) were included in the final statistical analysis of biochemical markers and metabolomics. RESULTS: Children conceived through FET had a lower level of fasting insulin level and HORM-IR and a higher level of fasting glucose and APOE as compared to children naturally conceived. Metabolomics showed that there were 16 small differential metabolites, mainly including amino acids, carnitines, organic acids, butyric, and secondary bile acid between two groups, which enriched in Nitrogen metabolism, Butanoate metabolism, Phenylalanine metabolism, and D-Arginine and D-ornithine metabolism pathways. CONCLUSION: Although the FET group had a significantly higher level of APOE and fasting glucose, it cannot yet be considered that children in the FET group had an obvious disorder of glucose and lipid metabolism. However, the potentially more active intestinal flora and lower carnitine levels of children in the FET group suggested by metabolomics are worth further exploration.

Effect of moxibustion at "Mingmen" (GV 4) and "Guanyuan" (CV 4) on immune function in healthy rats based on intestinal flora / 中国针灸

OBJECTIVE@#To observe the effects of moxibustion at "Mingmen" (GV 4) and "Guanyuan" (CV 4) on immune function and intestinal flora in healthy rats, thereby investigating the underlying mechanism of moxibustion on immune function.@*METHODS@#Twenty 8-week-old SD rats were randomly divided into a young blank group and a young moxibustion group, with 10 rats in each group. Similarly, twenty 8-month-old SD rats were randomly divided into a middle-aged blank group and a middle-aged moxibustion group, with 10 rats in each group. The rats in the two moxibustion groups received moxibustion at "Mingmen" (GV 4) and "Guanyuan" (CV 4), 15 min per session, once daily, five times a week, for a total of four months. The rats in the two blank groups were fed under normal conditions. After the intervention, thymus and spleen indexes were calculated; the morphology of thymus and spleen tissues was observed using HE staining; the flow cytometry was used to detect the expression of CD and CD T lymphocytes and the CD/CD ratio was calculated; ELISA was used to measure the serum levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-17 (IL-17); 16S rRNA high-throughput sequencing was used to analyze the intestinal flora. Additionally, the correlation between the relative abundance of intestinal flora and serum levels of TNF-α, IFN-γ, IL-6, IL-10 and IL-17 was analyzed.@*RESULTS@#Compared with the young blank group, the young moxibustion group exhibited an increase in the cortical area of thymus tissue with tighter lymphocyte arrangement; compared with the middle-aged blank group, the middle-aged moxibustion group showed an increase in thymus index (P<0.05) and an increase in the cortical area of thymus tissue. There were no significant differences in spleen index between the 2 moxibustion groups and the 2 blank groups (P>0.05). There were no significant differences in the expression of CD, CD, and CD/CD ratio between the 2 moxibustion groups and the corresponding blank groups (P>0.05). Compared with the young blank group, the young moxibustion group had elevated IL-6 level (P<0.05); compared with the middle-aged blank group, the middle-aged moxibustion group had decreased IL-10 and IL-17 levels (P<0.05). Compared with the young blank group, the young moxibustion group exhibited increased Sobs index, Ace index, and Chao index (P<0.01, P<0.05), as well as increased relative abundance of Spirochaetota, Treponema, Turicibacter, Rikenellaceae_RC9_gut_group (P<0.05), and decreased relative abundance of Dubosiella (P<0.05). Compared with the middle-aged blank group, the middle-aged moxibustion group had increased relative abundance of Spirochaetota, Treponema, norank_f_Peptococcaceae (P<0.05), and decreased relative abundance of Proteobacteria, Allobaculum, and Faecalibaculum (P<0.05). Correlation analysis revealed that relative abundance of Eubacterium_xylanophilum_group and unclassified _f_Lachnospiraceae was negatively correlated with serum TNF-α level (r=-0.39, P=0.03; r=-0.24, P=0.04), while relative abundance of norank_f_norank_o_Clostridia_UCG-014 and Lactobacillus was positively correlated with serum TNF-α level (r=0.37, P=0.04; r=0.43, P=0.02). The relative abundance of Roseburia and Monoglobus was negatively correlated with serum IFN-γ level (r=-0.40, P=0.02; r=-0.44, P=0.01), while relative abundance of Lactobacillus was positively correlated with serum IL-10 level (r=0.43, P=0.02).@*CONCLUSION@#Moxibustion could improve immune function in healthy rats, and its mechanism may be related to the regulation of relative abundance of intestinal flora.

[Characteristics of Xin'an medical masters in treatment of bi syndrome with acupuncture and moxibustion based on consolidating the root and cultivating the primary].

Based on the theory of consolidating the root and cultivating the primary, the paper collates and reviews the theoretical evidences and the characteristics of Xin'an medical masters in treatment of bi syndrome with acupuncture and moxibustion so as to provide the ideas for further research. Xin'an medical masters thoroughly acquainted with the theory of consolidating the root and cultivating the primary in treatment of bi syndrome with acupuncture and moxibustion, emphasizing the regulation of qi and blood, yin and yang, the nutrient qi and the defensive qi; and replenishing the middle jiao (spleen and stomach) and the lower jiao (kidney). The acupoint selection was distinctive, in which, the acupoints were selected and stimulated in terms of the etiology and the pathogenesis of diseases, as well as the properties of special points. The remarkable therapeutic effect on bi syndrome was ensured through specially selecting he-sea points, ashi points and "yin-yang opposite" points; effectively using the penetrating needling technique and moxibustion method and combining acupuncture with herbal medication.

Prognostic Biomarker KIF18A and Its Correlations With Immune Infiltrates and Mitosis in Glioma.

Background: Glioma is globally recognised as one of the most frequently occurring primary malignant brain tumours, making the identification of glioma biomarkers critically significant. The protein KIF18A (Kinesin Family Member 18A) is a member of the kinesin superfamily of microtubule-associated molecular motors and has been shown to participate in cell cycle and mitotic metaphase and anaphase. This is the first investigation into the expression of KIF18A and its prognostic value, potential biological functions, and effects on the immune system and mitosis in glioma patients. Methods: Gene expression and clinicopathological analysis, enrichment analysis, and immune infiltration analysis were based on data obtained from The Cancer Genome Atlas (TCGA), with additional bioinformatics analyses performed. Statistical analysis was conducted in R software. Clinical samples were used to evaluate the expression of KIF18A via immunohistochemical staining. In addition, the expression level of KIF18A was validated on U87 cell line. Results: Our results highlighted that KIF18A plays a key role as an independent prognostic factor in patients with glioma. KIF18A was highly expressed in glioma tissues, and KIF18A expression was associated with age, World Health Organization grade, isocitrate dehydrogenase (IDH) status, 1p/19q codeletion, primary therapy outcome, and overall survival (OS). Enrichment analysis revealed that KIF18A is closely correlated with the cell cycle and mitosis. Single sample gene set enrichment analysis (ssGSEA) analysis revealed that KIF18A expression was related to the immune microenvironment. The increased expression of KIF18A in glioma was verified in clinical samples and U87 cell line. Conclusion: The identification of KIF18A as a new biomarker for glioma could help elucidate how changes in the glioma cell and immune microenvironment promote glioma malignancy. With further analysis, KIF18A may serve as an independent prognostic indicator for human glioma.

CFTR Suppresses Neointimal Formation Through Attenuating Proliferation and Migration of Aortic Smooth Muscle Cells.

ABSTRACT: Cystic fibrosis transmembrane conductance regulator (CFTR) plays important roles in arterial functions and the fate of cells. To further understand its function in vascular remodeling, we examined whether CFTR directly regulates platelet-derived growth factor-BB (PDGF-BB)-stimulated vascular smooth muscle cells (VSMCs) proliferation and migration, as well as the balloon injury-induced neointimal formation. The CFTR adenoviral gene delivery was used to evaluate the effects of CFTR on neointimal formation in a rat model of carotid artery balloon injury. The roles of CFTR in PDGF-BB-stimulated VSMC proliferation and migration were detected by mitochondrial tetrazolium assay, wound healing assay, transwell chamber method, western blot, and qPCR. We found that CFTR expression was declined in injured rat carotid arteries, while adenoviral overexpression of CFTR in vivo attenuated neointimal formation in carotid arteries. CFTR overexpression inhibited PDGF-BB-induced VSMC proliferation and migration, whereas CFTR silencing caused the opposite results. Mechanistically, CFTR suppressed the phosphorylation of PDGF receptor ß, serum and glucocorticoid-inducible kinase 1, JNK, p38 and ERK induced by PDGF-BB, and the increased mRNA expression of matrix metalloproteinase-9 and MMP2 induced by PDGF-BB. In conclusion, our results indicated that CFTR may attenuate neointimal formation by suppressing PDGF-BB-induced activation of serum and glucocorticoid-inducible kinase 1 and the JNK/p38/ERK signaling pathway.

Supramolecular Radiosensitizer Based on Hypoxia-Responsive Macrocycle.

Radiotherapy (RT) has been viewed as one of the most effective and extensively applied curatives in clinical cancer therapy. However, the radioresistance of tumor severely discounts the radiotherapy outcomes. Here, an innovative supramolecular radiotherapy strategy, based on the complexation of a hypoxia-responsive macrocycle with small-molecule radiosensitizer, is reported. To exemplify this tactic, a carboxylated azocalix[4]arene (CAC4A) is devised as molecular container to quantitatively package tumor sensitizer banoxantrone dihydrochloride (AQ4N) through reversible host-guest interaction. Benefited from the selective reduction of azo functional groups under hypoxic microenvironment, the supramolecular prodrug CAC4A•AQ4N exhibits high tumor accumulation and efficient cellular internalization, thereby significantly amplifying radiation-mediated tumor destruction without appreciable systemic toxicity. More importantly, this supramolecular radiotherapy strategy achieves an ultrahigh sensitizer enhancement ratio (SER) value of 2.349, which is the supreme among currently reported noncovalent-based radiosensitization approach. Further development by applying different radiosensitizing drugs can make this supramolecular strategy become a general platform for boosting therapeutic effect in cancer radiotherapies, tremendously promising for clinical translation.

A unified operating procedure is crucial to evaluate sludge dewaterability, taking the setup of refrigerated storage time as an example.

Although extensive efforts have been carried out to study sludge dewatering mechanism, the lack of universal operating procedures makes it never be satisfactorily explained. This study evaluated the impact of a unified operating procedure on waste activated sludge (WAS) dewaterability by taking the setup of refrigerated storage time as an example. It was found that storage time played an important role in determining WAS dewaterability and sampled WAS should be refrigerated within 2 days. The results showed that after 2-d storage, sludge filterability was deteriorated significantly while the extent of dewatering efficiency had little change. Meanwhile, increasing storage time greatly increased the release of extracellular polymeric substances (EPS) and heavy metals, decreased sludge viscosity and weakened its network strength, but had little impact on the floc size and zeta potential of the sludge samples. It can hardly reveal the mechanism of storage time on sludge dewaterability due to the non-uniformity of operating procedures in literatures, which is normally ignored. This study emphasizes a unified operating procedure is crucial to evaluate WAS dewaterability. Therefore, more efforts shall be focused on establishing the uniform operating procedure while advancing applied research in the field of sludge dewatering.

Anxiety and depression-like behaviours are more frequent in aged male mice conceived by ART compared with natural conception.

The number of children born after assisted reproductive technology (ART) is accumulating rapidly, and the health problems of the children are extensively concerned. This study aims to evaluate whether ART procedures alter behaviours in male offspring. Mouse models were utilized to establish three groups of offspring conceived by natural conception (NC), in vitro fertilization and embryo transfer (IVF-ET), and frozen-thawed embryo transfer (IVF-FET), respectively. A battery of behaviour experiments for evaluating anxiety and depression levels, including the open field test (OFT), elevated plus maze (EPM) test, light/dark transition test (L/DTT), tail suspension test (TST), forced swimming test (FST), and sucrose preference test (SPT) was carried out. Aged (18 months old), but not young (3 months old), male offspring in the IVF-ET and IVF-FET groups, compared with those in the NC group, exhibited increased anxiety and depression-like behaviours. The protein expression levels of three neurotrophins in PFC or hippocampus in aged male offspring from the IVF-ET and IVF-FET groups reduced at different extent, in comparison to NC group. RNA sequencing (RNA-Seq) was performed in the hippocampus of 18 months old offspring to further explore the gene expression profile changes in the three groups. KEGG analyses revealed the coexisted pathways, such as PI3K-Akt signalling pathway, which potentially reflected the similarity and divergence in anxiety and depression between the offspring conceived by IVF-ET and IVF-FET. Our research suggested the adverse effects of advanced age on the psychological health of children born after ART should be highlighted in the future.

The role of the excitation:inhibition functional balance in the mPFC in the onset of antidepressants.

Currently available antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), generally require weeks to months to produce a therapeutic response, but the mechanism of action underlying the delayed onset of antidepressant-like action remains to be elucidated. The balance between excitatory glutamatergic pyramidal neurons and inhibitory γ-aminobutyric acid (GABA) interneurons, i.e., the excitation:inhibition functional (E:I) balance, in the medial prefrontal cortex (mPFC) is critical in regulating several behaviors and might play an important mediating role in the mechanism of rapid antidepressant-like action reported by several studies. In the present study, the multichannel electrophysiological technique was used to record the firing activities of pyramidal neurons and interneurons and investigate the effects of a single dose of fluoxetine and ketamine (both 10 mg/kg, i.p.) on the E:I functional balance in the rat mPFC after 90 min or 24 h, and the forced swimming test (FST) was used to evaluate the antidepressant-like effects of fluoxetine and ketamine. The present study also explored the effects of chronic treatment with fluoxetine (10 mg/kg, i.g.) for 7 d or 21 d on the E:I functional balance in the mPFC. The present results suggested that a single dose of ketamine could both significantly increase the firing activities of pyramidal neurons and significantly decrease the firing activities of interneurons in the mPFC and exerted significant antidepressant-like action on the FST after 90 min and 24 h, but fluoxetine had no such effects under the same conditions. However, chronic treatment with fluoxetine for 21 d (but not 7 d) could significantly affect the firing activities of pyramidal neurons and interneurons in the mPFC. Taken together, the present results indicated that rapid regulation of the E:I functional balance in the mPFC might be an important common mechanism of rapid-acting antidepressants and the delayed onset of SSRIs might be partly attributed to their inability to rapidly regulate the E:I functional balance in the mPFC. The present study provided a new entry point to the development of rapid-acting antidepressants.

Molluscicidal effect of immersion with 50% wettable powder of niclosamide ethanolamine salt against Oncomelania hupensis on the soil surface and inside the soil layer in winter / 中国血吸虫病防治杂志

Objective To evaluate the molluscicidal effect of 50% wettable powder of niclosamide ethanolamine salt (WPNES) against Oncomelania hupensis on the soil surface and inside the soil layer by immersion method in winter. Methods O. hupensis snails were placed on the soil surface and 2, 5 cm and 10 cm under the soil layer outdoors in winter, and then immersed in 50% WPNES at concentrations of 1 mg/L and 2 mg/L for 1, 3 d and 7 d, while dechlorinated water served as controls. Snail mortality was observed following immersion with 50% WPNES on the soil surface and inside the soil layer. Results Following immersion with 50% WPNES at concentrations of 2 mg/L and 1 mg/L outdoors in winter, the 3-day corrected snail mortality rates were 98.0% and 76.0% on the soil surface, and the 7-day corrected snail mortality rate was both 100.0%. Following immersion with 50% WPNES at concentrations of 2 mg/L and 1 mg/L outdoors in winter, the 7-day corrected snail mortality rates were 95.5% and 85.6% 2 cm below the soil layer, 66.0% and 6.4% 5 cm below the soil layer. However, the 7-day snail mortality rate swere comparable between the 50% WPNES treatment group (at 2 mg/L and 1 mg/L) and controls 10 cm below the soil layer (both P > 0.05). Conclusion Immersion of 50% WPNES at a concentration of 2 mg/L for 7 days presents a high molluscicidal efficacy against O. hupensis on the soil surface and 5 cm within the soil layers in winter.

The effect of blastomere loss during frozen embryo transfer on the transcriptome of offspring's umbilical cord blood.

Blastomere loss is a common issue during frozen-thawed embryo transfer (FET). Our previous study showed that blastomere loss was associated with an increased risk of small-for-gestational-age (SGA) neonates. The present study assessed the impact of blastomere loss during cryopreservation by comparing the mRNA profiles of umbilical cord blood of FET offspring from the prospective cohort study. Umbilical cord blood samples were collected from 48 neonates, including 12 from the loss group, 11 from the intact group, and 25 from the matched spontaneous pregnancy group. RNA-seq technology was used to compare the global gene expression profiles of the lymphocytes. Then, we used TopHat software to map the reads and quantitative real-time PCR to validate some important differentially expressed genes (DEGs). We identified 92 DEGs between the loss group and the spontaneous pregnancy group, including IGF2 and H19. Ingenuity Pathway Analysis (IPA) showed that the DEGs were most affected in the blastomere loss group. Downstream analysis also predicted the activation of organismal death pathways. In conclusions, our pilot study sheds light on the mechanism underlying how human blastomere loss may affect offspring at the gene expression level. These conclusions are, however, only suggestive, as the current study is based on a very limited sample size and type or nature of biological samples. Additional studies with larger sample sizes and independent experiments with placental samples should be conducted to verify these findings.

Evaluation of physical and neurocognitive development of infants conceived from frozen embryo transfer / 上海交通大学学报（医学版）

Objective • To evaluate the physical and neurocognitive development of infants conceived from frozen embryo transfer (FET). Methods • Two hundred and forty-eight infants (1.5-4 years old) conceived from FET and natural conception (NC) were recruited as the follow-up cohort of FET offspring, and their physical and neurocognitive development were followed up and evaluated. Multiple Logistic regression analysis was used to assess the potential risk of cognitive retardation in FET offspring. Results • There was no significant difference in composition ratio of Z score for height, weight and body mass index between the FET group and the NC control group. Multiple Logistic regression analysis showed that compared with the NC control group, the risk of neurocognitive development abnormalities and retardation was higher in the FET group, especially in fine motor (OR=3.01, 95%CI 1.48-6.11) and social development domains (OR=3.76, 95%CI 1.63-8.69); and in the FET group, the social development risk of female infants was higher than that of male infants. Conclusion • FET may exert a negative impact on the early neurocognitive development of infants.