Coixol mitigates Toxoplasma gondii infection-induced liver injury by inhibiting the Toxoplasma gondii HSP70/TLR4/NF-κB signaling pathway in hepatic macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Coix seed, the dry mature seed kernel of the gramineous plant coix (Coix lacryma-jobi L. var. ma-yuen Stapf), is widely consumed as a traditional Chinese medicine and functional food in China and South Korea. We have previously demonstrated the protective effect of coixol, a polyphenolic compound extracted from coix, against Toxoplasma gondii (T. gondii) infection-induced lung injury. However, the protective effect of coixol on hepatic injury induced by T. gondii infection have not yet been elucidated. AIM OF THE STUDY: This study explores the impact of coixol on T. gondii infection-induced liver injury and elucidates the underlying molecular mechanisms. MATERIALS AND METHODS: Female BALB/c mice and Kupffer cells (KCs) were employed to establish an acute T. gondii infection model in vivo and an inflammation model in vitro. The study examined coixol's influence on the T. gondii-derived heat shock protein 70 (T.g.HSP70)/toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway in T. gondii-infected liver macrophages. Furthermore, a co-culture system of KCs and NCTC-1469 hepatocytes was developed to observe the impact of liver macrophages infected with T. gondii on hepatocyte injury. RESULTS: Coixol notably inhibited the proliferation of tachyzoites and the expression of T.g.HSP70 in mouse liver and KCs, and attenuated pathological liver injury. Moreover, coixol decreased the production of high mobility group box 1, tumor necrosis factor-α, and inducible nitric oxide synthase by suppressing the TLR4/NF-κB signaling pathway in vitro and in vivo. Coixol also mitigated KCs-mediated hepatocyte injury. CONCLUSIONS: Coixol protects against liver injury caused by T. gondii infection, potentially by diminishing hepatocyte injury through the suppression of the inflammatory cascade mediated by the T.g.HSP70/TLR4/NF-κB signaling pathway in KCs. These findings offer new perspectives for developing coixol as a lead compound for anti-T. gondii drugs.

Efficacy of Ultrasound-Guided Intercostal Nerve Block on Pain Management and Physiological Outcomes in Breast Cancer Mastectomy: A retrospective study.

To evaluate the efficacy of ultrasound-guided intercostal nerve block in managing pain and physiological responses in patients undergoing radical mastectomy for breast cancer. A retrospective study analyzed 120 patients scheduled to undergo radical mastectomy in our hospital between January 2022 and December 2023. Depending on the type of anesthesia received, participants were assigned to the experimental group (60 patients) to receive ultrasound-guided intercostal nerve block and intravenous general anesthesia, or the control group (60 patients) to receive intravenous general anesthesia only. Both groups will utilize patient-controlled intravenous analgesia (PCIA) postoperatively. We will monitor and compare hemodynamic parameters, SpO2, and bispectral index (BIS) at multiple time points, and assess postoperative pain, inflammatory markers, PCIA utilization, and adverse reaction incidence. Comparative analysis showed distinct trends in heart rate, mean arterial pressure (MAP), BIS, and SpO2 across various surgical stages between groups. Notably, MAP values were consistently higher and less variable in the experimental group during surgery (P < .05). Pain assessments at 4, 12, and 24 hours postoperatively in both quiet and coughing states revealed significantly milder pain in the experimental group (P < .05). Preoperative inflammatory markers (PGE2, TNF-α, IL-6, MCP-1) were similar between groups; however, 24 hours post-surgery, the experimental group showed significantly lower levels of PGE2, IL-6, and MCP-1 (P < .05). Sufentanil consumption during surgery and PCIA use were notably lower in the experimental group (P < .05). The experimental group also experienced fewer anesthesia-related adverse reactions (8.33%) compared to the control group (25.00%) (P < .05). Ultrasound-guided intercostal nerve block significantly improves hemodynamic stability, reduces postoperative inflammatory markers, lowers the need for sufentanil, and minimizes adverse reactions in patients undergoing radical mastectomy for breast cancer.

Arctiin Mitigates Neuronal Injury by Modulating the P2X7R/NLPR3 Inflammasome Signaling Pathway.

Depression, recognized globally as a primary cause of disability, has its pathogenesis closely related to neuroinflammation and neuronal damage. Arctiin (ARC), the major bioactive component of Fructus arctii, has various pharmacological activities, such as anti-inflammatory and neuroprotective effects. Building on previous findings that highlighted ARC's capability to mitigate depression by dampening microglial hyperactivation and thereby reducing neuroinflammatory responses and cortical neuronal damage in mice, the current study delves deeper into ARC's therapeutic potential by examining its impact on hippocampal neuronal damage in depression. Utilizing both chronic unpredictable mild stress (CUMS)-induced depression model in mice and corticosterone (CORT)-stimulated PC12 cell model of neuronal damage, the techniques including Nissl staining, immunohistochemistry, western blotting, ELISA, lactate dehydrogenase assays, colony formation assays, immunofluorescence staining and molecular docking were employed to unravel the mechanisms behind ARC's neuroprotective effects. The findings revealed that ARC not only mitigates hippocampal neuropathological damage and reduces serum CORT levels in CUMS-exposed mice but also enhances cell activity while reducing lactate dehydrogenase release in CORT-stimulated PC12 cells. ARC attenuated neuroinflammatory responses and neuronal apoptosis by inhibiting the overactivation of the P2X7 receptor (P2X7R)/NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling pathway, similar to the effect of A438079 (P2X7R antagonist). Interestingly, pretreatment with A438079 blocked the neuroprotective effect of ARC. Computer modeling predicted that both ARC and A438079 have strong binding with P2X7R and they have the same binding site. These results suggested that ARC may exert a neuroprotective role by binding to P2X7R, thereby inhibiting the P2X7R/NLRP3 inflammasome signaling pathway.

A novel mechanism of resveratrol alleviates Toxoplasma gondii infection-induced pulmonary inflammation via inhibiting inflammasome activation.

BACKGROUND: Infection by Toxoplasma gondii can lead to severe pneumonia, with current treatments being highly inadequate. The NLRP3 inflammasome is one member of the NOD-like receptor family with a pyrin domain, which is crucial in the innate immune defense against T. gondii. Research has shown that resveratrol (RSV) prevents lung damage caused by this infection by inhibiting the T. gondii-derived heat shock protein 70/TLR4/NF-κB pathway, thus reducing the macrophage-driven inflammatory response. However, it should be mentioned that the participation of NLRP3 inflammasome in the immune response to the lung injuries caused by T. gondii infections is not entirely clear. PURPOSE: This study aims to clarify how RSV ameliorates lung damage triggered by Toxoplasma gondii infection, with a particular focus on the pathway involving TLR4, NF-κB, and the NLRP3 inflammasome. METHODS: Both in vitro and in vivo models of infection were developed by employing the RH strain of T. gondii in BALB/c mice and RAW 264.7 macrophage cell lines. The action mechanism of RSV was explored using techniques such as molecular docking, surface plasmon resonance, ELISA, Western blot, co-immunoprecipitation, and immunofluorescence staining. RESULTS: Findings indicate that the suppression of TLR4 or NF-κB impacts the levels of proteins associated with the NLRP3 inflammasome pathway. Additionally, a significant affinity for binding between RSV and NLRP3 was observed. Treatment with RSV led to a marked reduction in the activation and formation of the NLRP3 inflammasome within lung tissues and RAW 264.7 cells, alongside a decrease in IL-1ß concentrations in the bronchoalveolar lavage fluid. These outcomes align with those seen when using the NLRP3 inhibitor CY-09. Moreover, the application of CY-09 prior to RSV negated the latter's anti-inflammatory properties. CONCLUSION: Considering insights from previous research alongside the outcomes of the current investigation, it appears that the TLR4/NF-κB/NLRP3 signaling pathway emerges as a promising target for immunomodulation to alleviate lung injury from T. gondii infection. The evidence gathered in this study lays the groundwork for the continued exploration and potential future clinical deployment of RSV as a therapeutic agent with anti-Toxoplasma properties and the capability to modulate the inflammatory response.

The BTB-BACK-TAZ domain protein MdBT2 reduces drought resistance by weakening the positive regulatory effect of MdHDZ27 on apple drought tolerance via ubiquitination.

Drought stress is one of the dominating challenges to the growth and productivity in crop plants. Elucidating the molecular mechanisms of plants responses to drought stress is fundamental to improve fruit quality. However, such molecular mechanisms are poorly understood in apple (Malus domestica Borkh.). In this study, we explored that the BTB-BACK-TAZ protein, MdBT2, negatively modulates the drought tolerance of apple plantlets. Moreover, we identified a novel Homeodomain-leucine zipper (HD-Zip) transcription factor, MdHDZ27, using a yeast two-hybrid (Y2H) screen with MdBT2 as the bait. Overexpression of MdHDZ27 in apple plantlets, calli, and tomato plantlets enhanced their drought tolerance by promoting the expression of drought tolerance-related genes [responsive to dehydration 29A (MdRD29A) and MdRD29B]. Biochemical analyses demonstrated that MdHDZ27 directly binds to and activates the promoters of MdRD29A and MdRD29B. Furthermore, in vitro and in vivo assays indicate that MdBT2 interacts with and ubiquitinates MdHDZ27, via the ubiquitin/26S proteasome pathway. This ubiquitination results in the degradation of MdHDZ27 and weakens the transcriptional activation of MdHDZ27 on MdRD29A and MdRD29B. Finally, a series of transgenic analyses in apple plantlets further clarified the role of the relationship between MdBT2 and MdHDZ27, as well as the effect of their interaction on drought resistance in apple plantlets. Collectively, our findings reveal a novel mechanism by which the MdBT2-MdHDZ27 regulatory module controls drought tolerance, which is of great significance for enhancing the drought resistance of apple and other plants.

Synthesis and Antimicrobial Activity Evaluation of Pyridine Derivatives Containing Imidazo[2,1-b][1,3,4]Thiadiazole Moiety.

Four series of novel pyridine derivatives (17 a-i, 18 a-i, 19 a-e, and 20 a-e) were synthesized and their antimicrobial activities were evaluated. Of all the target compounds, almost half target compounds showed moderate or high antibacterial activity. The 4-F substituted compound 17 d (MIC=0.5 µg/mL) showed the highest antibacterial activity, its activity was twice the positive control compound gatifloxacin (MIC=1.0 µg/mL). For fungus ATCC 9763, the activities of compounds 17 a and 17 d are equivalent to the positive control compound fluconazole (MIC=8 µg/mL). Furthermore, compounds 17 a and 17 d showed little cytotoxicity to human LO2 cells, and did not show hemolysis even at ultra-high concentration (200 µM). The results indicate that these compounds are valuable for further development as antibacterial and antifungal agents.

Barriers and facilitators in implementing early essential newborn care of well-born babies in low- and middle-income countries: A mixed-method systematic review.

BACKGROUND: Evidences have demonstrated the effectiveness of early essential newborn care. However, the implementation of early essential newborn care is suboptimal. The aim is to identify and synthesise the barriers and facilitators impacting the implementation of early essential newborn care in low- and middle-income countries. DATA SOURCES: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, CINAHL, CNKI, Wan Fang Data, SinoMed and Google Scholar. METHODS: Two authors independently screened, performed quality assessment using the Mixed Methods Appraisal Tool and extracted data. This review includes papers that reported the barriers and facilitators of implementing early essential newborn care in low- and middle-income countries from the view of healthcare providers. Barriers and facilitators were coded according to the consolidated framework for implementation research in a deductive way and then been inducted into five common themes. This review followed synthesis without meta-analysis reporting guideline. RESULTS: A total of 28 studies were included. Five inductive common themes influencing implementing early essential newborn care in low- and middle-income countries were system-level healthcare factors, healthcare providers' knowledge and beliefs, the requirements of mothers or families, adapting to routine practice and the working climate of organisation. CONCLUSION: The factors were from system level, facility level and individual level and were inducted into five themes. Based on this review, decision-makers could tailor implementing strategies to narrow the gap between the evidence and implementation. RELEVANCE TO CLINICAL PRACTICE: The study offers guidance for health professionals to identify barriers and facilitators in implementing early essential newborn care and make tailored strategies when implementing early essential newborn care. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contributions.

Retrieval of Trophoblast Cells from the Cervical Canal: A Promising Non-invasive Method for Prenatal Diagnosis.

Background: Extravillous trophoblasts (EVTs) cells have shown promise for their application in non-invasive prenatal diagnosis during the first trimester. The Trophoblast Retrieval and Isolation from the Cervix (TRIC) method allows for the isolation of homogeneous trophoblast cells from pregnant women as early as 5 weeks gestation. Objective: This study aimed to explore the potential value of extravillous trophoblast cells collected from the cervix, enriched, and purified using the TRIC method for first-trimester prenatal diagnosis. Methods: A prospective observational study was conducted, and we collected extravillous trophoblast cells from the cervixes of 100 pregnant women between 5-7 weeks gestation before an induced abortion. Subsequently, these cells underwent STR analysis and fluorescence in situ hybridization (FISH). Results: Out of the 100 cases, trophoblast cells were successfully collected from 96 cases. Among them, STR analysis revealed maternal cell contamination in 13 cases. Gender determination using FISH showed 44 male cases (including one case with 47, XY, +21) and 39 female cases (including one case with 47, XXX). The results of the FISH examination of these 83 cases were in concordance with those of the villi FISH examination. Conclusions: The collection of fetal trophoblast cells from the cervix represents a feasible and non-invasive approach for first-trimester prenatal diagnosis. The TRIC method enables efficient enrichment and purification of trophoblast cells, which can be of significant benefit for subsequent diagnosis using the FISH method.

Effect of nalbuphine plus ropivacaine on vaginal labor in epidural analgesia.

BACKGROUND: Various approaches using epidural analgesia have been employed for relieving labor pain and promoting spontaneous delivery. We aimed to evaluate the effect of nalbuphine and ropivacaine versus fentanyl and ropivacaine on the duration of delivery in parturients. METHODS: Clinical data of 160 full-term primiparous women who received either nalbuphine or fentanyl in combination with ropivacaine infusion for epidural labor analgesia in our hospital from December 2020 to May 2022 were retrospectively analyzed. The participants were divided into two groups based on anesthesia methods: nalbuphine group (NR group, n = 78) received 0.2 mg/mL nalbuphine combined with 0.1% ropivacaine hydrochloride for patient-controlled epidural analgesia (PCEA) and fentanyl group (FR group, n = 82) received 2 ug/mL fentanyl citrate and 0.1% ropivacaine hydrochloride for PCEA. Both groups received an epidural blockade for labor analgesia at lumbar 2-3 interspace. The duration of the first, second, and third stages of labor, the onset of analgesia, and time before delivery (T0), 15 min of analgesia (T1), 30 min of analgesia (T2), full opening of the uterine opening (T3),exerts force during childbirth(T4), heart rate (HR), blood pressure (BP), blood saturation (SpO2), visual analogue pain scale (VAS) score, Ramsay sedation score, and modified Bromage score, and 5 min were recorded at 2 h postpartum (T5). The neonatal Apgar score, neonatal behavioral neurological assessment (NBNA) score, maternal nausea, vomiting, and itchy skin were recorded. RESULTS: Compared with the FR group, the first stage of labor duration (p < 0.05) and total duration of labor (p < 0.05) were shortened and the onset of analgesia (p < 0.05) was increased in the NR group. NR group had lower incidence of urinary retention than FR group (p < 0.05). The maternal and neonatal investigational parameters and scores had no significant difference between the two groups. CONCLUSIONS: Nalbuphine combined with ropivacaine in epidural block labor has a faster onset of analgesia and has a lower incidence of urinary retention than fentanyl combined with ropivacaine, and nalbuphine shortens the duration of the first and total stages of labor. Both nalbuphine and fentanyl can reduce pain during labor, have little effect on maternal hemodynamics, and have no significant effect on neonatal Apgar or NBNA scores.

Synthesis of AgBr/Ti3C2@TiO2 ternary composite for photocatalytic dehydrogenation of 1,4-dihydropyridine and photocatalytic degradation of tetracycline hydrochloride.

In this work, AgBr/Ti3C2@TiO2 ternary composite photocatalyst was prepared by a solvothermal and precipitation method with the aims of introducing Ti3C2 as a cocatalyst and TiO2 as a compositing semiconductor. The crystal structure, morphology, elemental state, functional groups and photoelectrochemical properties were studied by XRD, SEM, TEM, XPS, FI-IR and EIS. The photocatalytic performances of the composites were investigated by the photodehydrogenation of diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate (1,4-DHP) and the photodegradation of tetracycline hydrochloride (TCH) under visible light irradiation (λ > 400 nm). The AgBr/Ti3C2@TiO2 composite photocatalyst showed enhanced photocatalytic performance in both photocatalytic reactions. The photocatalytic activity of the composite photocatalyst is dependent on the proportional content of Ti3C2@TiO2. With optimized Ti3C2@TiO2 proportion, the photocatalytic ability of the AgBr/Ti3C2@TiO2 composite was 24.5 times as high as that of Ti3C2@TiO2 for photodehydrogenation of 1,4-DHP and 1.9 times as high as that of pure AgBr for photodegradation of TCH. The enhanced photocatalytic performance of the AgBr/Ti3C2@TiO2 composite should be due to the formation of a p-n heterojunction structure between AgBr and Ti3C2@TiO2 and the excellent electronic properties of Ti3C2, which enhanced the visible light absorption capacity, lowered the internal resistance, speeded up the charge transfer and reduced the recombination efficiency of photo-generated carriers. Mechanism studies showed that superoxide free radical (˙O2-) was the main active species. In addition, the composite photocatalyst also displayed good stability, indicating its reutilization in practical application.

Clinical application of ultrasound-guided thoracic nerve block in the operation of benign breast tumors.

OBJECTIVE: To analyze the application of ultrasound-guided thoracic nerve block (TNB) in the operation of benign breast tumors. METHODS: A retrospective analysis was conducted on 69 patients who underwent resection of benign breast tumors (fibroma, segment) in the Maternity and Child Care Center of Qinhuangdao from January 2021 to June 2022. Among them, 33 patients who received TNB were assigned to an observation group, and 36 patients who received local infiltration anesthesia were assigned to a control group. The heart rate (HR) and systolic blood pressure (SBP) and diastolic blood pressure (DBP) of patients were recorded before anesthesia (T0), at skin incision (T1), at 0.5 h after operation (T2) and before leaving the operating room (T3). We also recorded the operation indexes, comprising operation time, total propofol dosage administered during operation, anesthesia recovery time and extubation time. The visual analogue scale (VAS) score was evaluated at 0.5, 2, 4 and 6 h after the operation. The two groups were also compared in terms of the levels of immunoglobulin (Ig) A, IgG, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The postoperative adverse reactions in the two groups were statistically analyzed. RESULTS: Compared with the observation group, the control group experienced a longer operation time, anesthesia recovery time and extubation time and consumed more propofol (P < 0.001). At T0 and T1, the two groups were not notably different in SBP, DBP and HR (P > 0.05), but at T2 and T3, the control group showed higher SBP, DBP and HR than the observation group (P < 0.001). The control group exhibited notably higher VAS scores than the observation group (P < 0.001). Before operation, the differences in the levels of IgA, IgG, IL-6 and TNF-α were not significantly different between the two groups (P > 0.05), while after operation and at 24 h after operation, the control group showed higher levels of IgA, IgG, IL-6 and TNF-α in comparison to the observation group (P < 0.01). The incidences of adverse reactions were not significantly different between the two groups (P > 0.05). CONCLUSION: Ultrasound-guided TNB can substantially reduce both the operation time and the postoperative pain in patients with benign breast tumors, without increasing the incidence of adverse reactions.

Polyacrylonitrile nanofibrous membrane composited with zeolite imidazole skeleton-8 and silver nanoclusters for efficient antibacterial and emulsion separation.

Oily wastewater discharged by industrial development is an important factor causing water pollution. Membrane separation technology has the advantages of low cost, simple operation, and high efficiency in the treatment of oily wastewater. However, membrane materials are easily eroded by microorganisms during long-term storage or use, thereby resulting in reduced separation efficiency. Herein, a zeolite imidazole skeleton-8@silver nanocluster composite polyacrylonitrile (ZIF-8@AgNCs/PAN) nanofibrous membrane was fabricated by electrospinning and in situ growth technology. The surface chemistry, morphology, and wettability of the composite membranes were characterized. The carboxyl groups on the surface of hydrolyzed PAN nanofibers, which can be complexed with zinc ions (Zn2+), are utilized as growth sites for porous metal organic frameworks (ZIF-8). Meanwhile, AgNCs are loaded into ZIF-8 to achieve stable hybridization of ZIF-8@AgNCs and nanofibers. The loading quantity of ZIF-8@AgNCs, which can dominantly affect the surface roughness and the porosity of the membranes, is regulated by the feeding amount of AgNCs. The ZIF-8@AgNCs/PAN membrane achieves effective oil-water separation with high separation efficiency toward petroleum ether-in-water emulsion (98.6%) and permeability (62 456 ± 1343 Lm-2 h-1 bar-1). Furthermore, the ZIF-8@AgNCs/PAN membrane possesses high antibacterial activity against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus), which is beneficial for the long-term storage and use of the membrane.

Ethylene inhibits malate accumulation in apple by transcriptional repression of aluminum-activated malate transporter 9 via the WRKY31-ERF72 network.

Malic acid accumulation in the vacuole largely determines acidity and perception of sweetness of apple. It has long been observed that reduction in malate level is associated with increase in ethylene production during the ripening process of climacteric fruits, but the molecular mechanism linking ethylene to malate reduction is unclear. Here, we show that ethylene-modulated WRKY transcription factor 31 (WRKY31)-Ethylene Response Factor 72 (ERF72)-ALUMINUM ACTIVATED MALATE TRANSPORTER 9 (Ma1) network regulates malate accumulation in apple fruit. ERF72 binds to the promoter of ALMT9, a key tonoplast transporter for malate accumulation of apple, transcriptionally repressing ALMT9 expression in response to ethylene. WRKY31 interacts with ERF72, suppressing its transcriptional inhibition activity on ALMT9. In addition, WRKY31 directly binds to the promoters of ERF72 and ALMT9, transcriptionally repressing and activating ERF72 and ALMT9, respectively. The expression of WRKY31 decreases in response to ethylene, lowering the transcription of ALMT9 directly and via its interactions with ERF72. These findings reveal that the regulatory complex WRKY31 forms with ERF72 responds to ethylene, linking the ethylene signal to ALMT9 expression in reducing malate transport into the vacuole during fruit ripening.

Synergistic effect of glutathione and IgG4 in immune evasion and the implication for cancer immunotherapy.

BACKGROUND: We recently reported a novel IgG4-centered immune evasion mechanism in cancer, and this was achieved mostly through the Fc-Fc reaction of increased IgG4 to cancer-bound IgG in cancer microenvironment. The mechanism was suggested to be related to cancer hyperprogressive disease (HPD) which is a side-effect often associated to IgG4 subtype PD-1 antibody immunotherapy. HPD was reported to occur in cancers with certain mutated genes including KRAS and such mutations are often associated to glutathione (GSH) synthesis. Therefore, we hypothesize that IgG4 and GSH may play a synergistic role in local immunosuppression of cancer. METHODS: Quantitatively analyzed the distribution and abundance of GSH and IgG4 in human cancer samples with ELISA and immunohistochemistry. The interactions between GSH and IgG4 were examined with Electrophoresis and Western Blot. The synergistic effects of the two on classic immune responses were investigated in vitro. The combined effects were also tested in a lung cancer model and a skin graft model in mice. RESULTS: We detected significant increases of both GSH and IgG4 in the microenvironment of lung cancer, esophageal cancer, and colon cancer tissues. GSH disrupted the disulfide bond of IgG4 heavy chain and enhanced IgG4's ability of Fc-Fc reaction to immobilized IgG subtypes. Combined administration of IgG4 and GSH augmented the inhibitory effect of IgG4 on the classic ADCC, ADCP, and CDC reactions. Local administration of IgG4/GSH achieved the most obvious effect of accelerating cancer growth in the mouse lung cancer model. The same combination prolonged the survival of skin grafts between two different strains of mouse. In both models, immune cells and several cytokines were found to shift to the state of immune tolerance. CONCLUSION: Combined application of GSH and IgG4 can promote tumor growth and protect skin graft. The mechanism may be achieved through the effect of the Fc-Fc reaction between IgG4 and other tissue-bound IgG subtypes resulting in local immunosuppression. This reaction was facilitated by increased GSH to dissociate the two heavy chains of IgG4 Fc fragment at its disulfide bonds. Our findings unveiled the interaction between the redox system and the immune systems in cancer microenvironment. It offers a sensible explanation for HPD and provides new possibilities for manipulating this mechanism for cancer immunotherapy.

Prenatal diagnosis and molecular cytogenetic characterization of an inherited microdeletion of 18q12.3 encompassing SETBP1.

The 18q12.3 region contains the SET binding protein 1 (SETBP1) gene. SETBP1 mutations or deletions are associated with Schinzel-Giedion syndrome or intellectual developmental disorder, autosomal dominant 29. We report the prenatal diagnosis and genetic counseling of a patient with a maternally inherited 18q12.3 microdeletion. In this family, the mother and son carried the same microdeletion. Chromosomal microdeletions and microduplications are difficult to detect using conventional cytogenetics, whereas the combination of prenatal ultrasound, karyotype analysis, chromosomal microarray analysis, and genetic counseling is helpful for the prenatal diagnosis of chromosomal microdeletions/microduplications.

MdbHLH3 modulates apple soluble sugar content by activating phosphofructokinase gene expression.

Sugars are involved in plant growth, fruit quality, and signaling perception. Therefore, understanding the mechanisms involved in soluble sugar accumulation is essential to understand fruit development. Here, we report that MdPFPß, a pyrophosphate-dependent phosphofructokinase gene, regulates soluble sugar accumulation by enhancing the photosynthetic performance and sugar-metabolizing enzyme activities in apple (Malus domestica Borkh.). Biochemical analysis revealed that a basic helix-loop-helix (bHLH) transcription factor, MdbHLH3, binds to the MdPFPß promoter and activates its expression, thus promoting soluble sugar accumulation in apple fruit. In addition, MdPFPß overexpression in tomato influenced photosynthesis and carbon metabolism in the plant. Furthermore, we determined that MdbHLH3 increases photosynthetic rates and soluble sugar accumulation in apple by activating MdPFPß expression. Our results thus shed light on the mechanism of soluble sugar accumulation in apple leaves and fruit: MdbHLH3 regulates soluble sugar accumulation by activating MdPFPß gene expression and coordinating carbohydrate allocation.

The apple bHLH transcription factor MdbHLH3 functions in determining the fruit carbohydrates and malate.

Changes in carbohydrates and organic acids largely determine the palatability of edible tissues of horticulture crops. Elucidating the potential molecular mechanisms involved in the change in carbohydrates and organic acids, and their temporal and spatial crosstalk are key steps in understanding fruit developmental processes. Here, we used apple (Malus domestica Borkh.) as research materials and found that MdbHLH3, a basic helix-loop-helix transcription factor (bHLH TF), modulates the accumulation of malate and carbohydrates. Biochemical analyses demonstrated that MdbHLH3 directly binds to the promoter of MdcyMDH that encodes an apple cytosolic NAD-dependent malate dehydrogenase, activating its transcriptional expression, thereby promoting malate accumulation in apple fruits. Additionally, MdbHLH3 overexpression increased the photosynthetic capacity and carbohydrate levels in apple leaves and also enhanced the carbohydrate accumulation in fruits by adjusting carbohydrate allocation from sources to sinks. Overall, our findings provide new insights into the mechanism of how the bHLH TF MdbHLH3 modulates the fruit quality. It directly regulates the expression of cytosolic malate dehydrogenase MdcyMDH to coordinate carbohydrate allocation and malate accumulation in apple.

A study of multinucleated giant cells in esophageal cancer.

OBJECTIVES: To evaluate the occurrence, abundance, distribution, nature and clinical significance of multinucleated giant cell (MGC) in esophageal cancer. MATERIALS AND METHODS: MGCs were examined with conventional pathology, immunohistochemistry and immunofluorescence in 107 esophageal cancer tissues. The findings were correlated to pathological diagnosis and clinical behavior of the cancers. RESULTS: MGCs were identified in 31.7% (34/107) of the cases. MGCs were positive for CD11c, CD11b, CD32, CD16, HLA-DR and MMP9, and negative for CD163, CD206 and CD64 giving a molecular profile of proinflammatory M1 but not immunosuppressive M2. MGCs were significantly related to decreased lymph node metastasis (p = 0.011), low pTNM stage (p = 0.044), favorable survival (p = 0.04), squamous cell cancer type rather than other histopathological subtypes (p = 0.020) and associated to better differentiation (p = 0.063). CONCLUSIONS: MGCs belong to M1 macrophage and perform phagocytosis and scavenging of cancer cells that would benefit patients' survival and could serve as a prognostic marker.