Exploring and validating heating dynamics in a radio-frequency electromagnetic field-based resonant chamber for mouse hyperthermia research.

Mild whole-body hyperthermia has been shown to have anti-tumor effects through an immune-modulating mechanism. Before it is widely applied in the clinic, tremendous mechanistic research in animals is necessary to adhere to evidence-based principles. The radio frequency electromagnetic field (RF-EMF) based heating facility could be a good choice for hyperthermia treatment, but the heating characteristics of a facility, including structure design, electromagnetic and thermal dosimetry, and the biologic effects of hyperthermia, need to be well elucidated. Here, we reported the heating characteristic study on a resonant chamber (RC) excited by a 1800 MHz solid source. The EMF in the RC was stirred by 24 static reflectors, which resulted in the standard deviation of electric field intensity being below 3 dB in the EM homogeneity evaluation. For the exposure scenario, six free-moving mice were loaded into separate cases and exposed simultaneously in the RC. The EMF energy absorption and distribution in exposed mice were calculated with the 12-plane-waves method of numerical simulation. Different levels of core body temperature increment in exposed mice were achieved through regulation of the source output power. Overexpression of heat shock proteins (HSPs) was detected in the liver, lung and muscle, but not in the brain of the exposed mice. The levels of representative inflammatory cytokines in the serum, TNF-α and IL-10 increased post RC exposure. Based on the heating characteristic study and validation, the applied RC would be a qualified heating system for mild whole-body hyperthermia effect research in mice.

Mild whole-body hyperthermia has potential anti-tumor effects by modulating the immune system. A radio frequency electromagnetic field (RF-EMF)-based heating facility emerges as a suitable option for hyperthermia treatment. However, a qualified heating facility for scientific research must elucidate its heating characteristics and validate the biological effects associated with hyperthermia. In this study, we report the characteristics of a rodent heating chamber using EMF energy. The special structure of the chamber not only achieved efficient EMF usage but also ensured the homogeneity in EMF spatial distribution, animal EM absorption, and EMF-caused biological effects. Our work may offer insights for designing a low-cost yet reliable heating facility for scientific research.

Comprehensive genomic analyses of Vigna unguiculata provide insights into population differentiation and the genetic basis of key agricultural traits.

Vigna unguiculata is an important legume crop worldwide. The subsp. sesquipedalis and unguiculata are the two major types grown; the former is mainly grown in Asia to produce fresh pods, while the latter is mainly grown in Africa to produce seeds. Here, a chromosome-scale genome for subsp. sesquipedalis was generated by combining high-fidelity (HiFi) long-read sequencing with high-throughput chromosome conformation capture (Hi-C) technology. The genome size for all contigs and N50 were 594 and 18.5 Mb, respectively. The Hi-C interaction map helped cluster 91% of the contigs into 11 chromosomes. Genome comparisons between subsp. sesquipedalis and unguiculata revealed extensive genomic variations, and some variations resulted in gene loss. A germplasm panel with 315 accessions of V. unguiculata was resequenced, and a genomic variation map was constructed. Population structure and phylogenetic analyses suggested that subsp. sesquipedalis originated from subsp. unguiculata. Highly differentiated genomic regions were also identified, and a number of genes functionally enriched in adaptations were located in these regions. Two traits, pod length (PL) and pod width (PW), were observed for this germplasm, and genome-wide association analysis of these traits was performed. The quantitative trait loci (QTLs) for these two traits were identified, and their candidate genes were uncovered. Interestingly, genomic regions of PL QTLs also showed strong signals of artificial selection. Taken together, the results of this study provide novel insights into the population differentiation and genetic basis of key agricultural traits in V. unguiculata.

Unraveling the Chemistry of High Valent Arylcopper Compounds and Their Roles in Copper-Catalyzed Arene C-H Bond Transformations Using Synthetic Macrocycles.

Recent decades have witnessed a resurgence of the study of copper-catalyzed organic reactions. As the surrogate of noble metal catalysts, copper salts have been shown to exhibit remarkable versatility in activating various C-H bonds enabling the construction of diverse carbon-carbon and carbon-heteroatom bonds. Advantageously, copper salts are also naturally abundant, inexpensive, and less toxic in comparison to precious metals. Despite significant developments in synthesis, the mechanism of copper catalysis remains elusive. Hypothetical pathways such as the two-electron Cu(III)/Cu(I) and Cu(II)/Cu(0) catalytic cycles and the one-electron Cu(II)/Cu(I) catalytic cycle have been invoked to diagram C-H bond transformations because of the formidable challenges to isolate and characterize transient high valent organocopper intermediates. In fact, organocopper chemistry has been dominated for a long time by the acknowledged nucleophilic organocopper(I) compounds. Since the beginning of the new millennium, we have been systematically studying the supramolecular chemistry of heteracalix[n]aromatics. Owing to the ease of their synthesis and selective functionalizations, self-tunable conformation and cavity structures resulting from the interplay of heteroatoms with aromatic subunits, and outstanding properties in molecular recognition and self-assembly, heteracalix[n]aromatics have become a class of privileged synthetic macrocyclic hosts. Our journey to the chemistry of high valent organocopper compounds started with a serendipitous discovery of the facile formation of a stable organocopper compound, which contains astonishingly a Ph-Cu(III) σ-bond under very mild aerobic conditions. When we examined routinely the effect of the macrocyclic structures on noncovalent complexation properties, titration of tetraazacalix[1]arene[3]pyridine with Cu(ClO4)2·6H2O resulted in the precipitation of dark-purple crystals of phenylcopper(III) diperchlorate. Our curiosity about the transformation of an arene C-H bond into an Ar-Cu(III) bond prompted us to conduct an in-depth investigation of the reaction of macrocyclic arenes with copper(II) salts, leading to the isolation of arylcopper(II) compounds which are unprecedented and the missing link in organocopper chemistry. With structurally well-defined organometallics in hand, we have explored extensively the reactivities of both arylcopper(II) and arylcopper(III) compounds, demonstrating their versatility and uniqueness in chemical synthesis. Novel and fascinating arene C-H transformations under copper catalysis have been developed. Using acquired high valent arylcopper compounds as molecular probes, and employing the functionalizations of tetraazacalix[1]arene[3]pyridines as model reactions, we have revealed the diverse mechanisms of copper-promoted arene C-H bond reactions. Elusive reaction pathways of some copper-catalyzed C-X bond activations have also been unraveled. In the meantime, we have also witnessed pleasingly the rapid development of field with the advent of new high valent organocopper compounds. Without any doubt, studies of the synthesis, reactivity, and catalysis of high valent organocopper compounds have been reshaping the field of organocopper chemistry. This Account summarizes our endeavors to explore the chemistry of structurally well-defined arylcopper(II) and arylcopper(III) compounds and the mechanisms of copper-catalyzed arene C-H and C-X bond transformations. We hope this Account will inspire chemists to study thoroughly the fundamentals and the cutting-edge catalysis of high valent organocopper compounds advancing and redefining the discipline of organocopper chemistry.

Exploring core symptoms and interrelationships among symptoms in children with acute leukemia during chemotherapy: A network analysis.

PURPOSE: Children with acute leukemia have suffered from a considerable symptom burden during chemotherapy. However, few studies have focused on exploring the mechanisms among symptoms in children with acute leukemia. Our study aims to explore core symptoms and describe the interrelationships among symptoms in children with acute leukemia during chemotherapy. METHODS: From January 2021 to March 2023, 469 children with acute leukemia were recruited from 20 Chinese cities. The Memorial Symptom Assessment Scale 10-18 (MSAS 10-18) was used to evaluate the prevalence and severity of symptoms during chemotherapy. A network analysis was performed by the R software based on 31 symptoms. Centrality indices and density were used to explore core symptoms and describe interrelationships among symptoms in the network during chemotherapy. RESULTS: Worrying and feeling irritable were the central symptoms across the three centrality indices, including strength, closeness, and betweenness. Lack of energy was the most prevalent symptom; however, it was less central than other symptoms. The density of the "induction and remission" network significantly differed from other cycles' counterparts (p < 0.001). Global strength was greater in the " ≥ 8 years group " network than the " < 8 years group " network (p = 0.023). CONCLUSION: Network analysis provides a novel approach to identifying the core symptoms and understanding the interrelationships among symptoms. Our study indicates the need to assess emotional symptoms in children with acute leukemia during chemotherapy, especially during the induction and remission phases, as well as in older children. Future research is imperative to construct trajectories of dynamic symptom networks and centrality indices in longitudinal data to investigate the causal relationships among symptoms.

Fasting blood glucose predicts high risk of in-stent restenosis in patients undergoing primary percutaneous coronary intervention: a cohort study.

Objectives. Studies have shown that fasting blood glucose (FBG) is closely associated with poor prognosis in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI), but its association with in-stent restenosis (ISR) is still unclear. Therefore, this study was to explore the association between FBG with ISR in patients with CHD after PCI. Design. In this cohort study, we included 531 patients with CHD who underwent PCI. Logistic regression, receiver operating characteristic (ROC), subgroup analysis and restricted cubic spline (RCS) were used to assess the association between FBG with ISR. Results. A total of 124 (23.4%) patients had ISR. Patients with higher levels of FBG had higher incidence of ISR compared to those with lower levels of FBG (p = 0.002). In multivariable logistic regression analyses, higher levels of FBG remained strongly associated with higher risk of ISR (as a categorical variable, OR: 1.89, 95% CI: 1.21-2.94, p = 0.005; as a continuous variable, OR: 1.12, 95% CI: 1.03-1.23, p = 0.011). ROC analysis also showed that FBG might be associated with the occurrence of ISR (AUC = 0.577, 95% CI: 0.52-0.64, p = 0.013). Subgroup analyses showed the association of FBG with ISR was also stable in several subgroups (< 60 years or ≥ 60 years, male, with or without smoking, without diabetes and without hypertension). And RCS analysis showed that FBG was linearly and positively associated with the risk of ISR. Conclusions. Higher levels of FBG were closely associated with higher risk of ISR in patients with CHD after PCI.

Clinical Efficacy of Detailed Intervention After Clopidogrel Treatment and Analysis of Angina Relief in Patients with CHD.

Objective: Coronary heart disease is incurable and prone to recurrence, and long-term dependence on medication and good nursing management to improve the prognosis. The effect of clopidogrel in the treatment of coronary heart disease is affected by many factors, so paying more attention to details in the process of patient care is conducive to creating more ideal recovery conditions for patients. The purpose of this study is to conduct detailed intervention for coronary heart disease (CHD) after clopidogrel treatment, and to analyze the clinical efficacy of this intervention mode on CHD patients and the relief of angina pectoris. Methods: A total of 120 patients with coronary heart disease who were diagnosed and treated in our hospital from May 2020 to March 2022 were selected as the research objects and divided into a detail group (n=60) and a routine group (n=60) according to the computer randomization method, All research subjects were given clopidogrel intervention, followed by routine intervention in the routine group, and detailed intervention in the detail group. Detailed intervention includes specific measures such as psychological intervention, life intervention, health education, medical assessments, personalized care. The control of angina pectoris of the subjects was analyzed, and the daily life, motor function, quality of life score, negative emotion score and complications were observed. Results: The dimension score of TS [(83.50±5.14) points vs (77.42±4.35) points], DP [(85.59±5.78) points vs (80.14±5.43) points], PL [(79.62±5.19) points vs (74.18±5.04) points], AS [(90.69±6.35) points vs (85.57±6.12) points], AF[(83.54±5.22) points vs (77.51±5.16) points] in the detail group were higher than those of conventional group (P < .001). The differences in daily life, motor function of the subjects before the intervention were not comparable (P > .05), and the scores of daily life [(86.14±5.52) points vs (65.48±5.17) points] and motor function [(88.97±5.34) points vs (70.58±5.46) points] in the detail group at 4 weeks after intervention were higher than those in the routine group (P < .001). The quality of life in the detail group [mental state of (17.56±2.12) points vs (20.13±2.09) points, mental health of (15.62±2.34) points vs (18.09±2.06) points, social function of (15.86±2.41) points vs (18.11±2.14) points, emotional function of (14.36±3.45) points vs (16.78±3.69) points] were lower than those of the conventional group (P < .001). The negative mood scores [SAS score of (41.70±3.14) points vs (67.14±3.25) points, SDS score of (39.59±4.11) points vs (60.58±4.54) points] in the detail group were lower than those of the conventional group (P < .001). In addition, the total incidence of complications (3.33% vs 13.33%) in the detail group was significantly lower than that in the regular group (P < .001). Conclusions: Detailed intervention after clopidogrel treatment in CHD patients can significantly improve the efficacy of patients, reduce angina pectoris, and at the same time can effectively improve various physical functions and relieve their negative emotions, which is worthy of being widely used in clinical practice. Better control of angina pectoris is beneficial to reduce the frequency of hospital admission and save medical resources. The sample size of this study is small, and the sample size will be further expanded in the future to improve the scientific conclusion.

Manganese overexposure induces Parkinson-like symptoms, altered lipid signature and oxidative stress in C57BL/6 J mouse.

Although adequate intake of manganese (Mn) is essential to humans, Mn in excess is neurotoxic. Exposure to extremely high doses of Mn results in "manganism", a condition that exhibits Parkinson-like symptoms. However, the mechanisms underlying its neurotoxic effects in Mn-induced parkinsonism pathogenesis are unclear. In this study, 8-week-old male C57BL/6 J mice were injected intraperitoneally with saline and 50 mg/kg MnCl2 respectively once daily for 14 days to produce an acute Mn neurotoxicity model. Accumulation of Mn in the midbrain, motor dysfunction and loss of dopaminergic neurons in the substantia nigra evidenced Mn neurotoxicity. Untargeted lipidomic analysis demonstrated that Mn overexposure altered lipidome profiles. A significant modulation of 12 lipid subclasses belonging to 5 different categories were found in the midbrain and among the most abundant lipids were sphingolipids, glycerophospholipids, and glycerides. The levels of sphingomyelin (SM) were significantly decreased after Mn treatment. The expression of SM biosynthesis genes was decreased dramatically while sphingomyelinase was up-regulated. In addition, we observed oxidative stress in both the midbrain of mice and MN9D cells, indicated by the increase of MDA level, the decrease of reduced GSH level and the inhibition of SOD and GPx enzyme activities. There was a correlation between these changes and motor dysfunctions. Overall, our study is the first to use lipidomics techniques to explore the pathogenesis of Mn-induced parkinsonism in C57BL/6 J mice. Mn induced molecular events in the midbrain, such as lipid metabolism disorders, oxidative stress and dopaminergic neurons injury, may mechanistically play important roles in the pathogenesis of Parkinson-like symptoms. Moreover, these findings emphasize the necessity for reducing the health risk of environmental neurotoxic pollutants in relation to parkinsonism.

The Ralstonia solanacearum Type III Effector RipAW Targets the Immune Receptor Complex to Suppress PAMP-Triggered Immunity.

Bacterial wilt, caused by Ralstonia solanacearum, one of the most destructive phytopathogens, leads to significant annual crop yield losses. Type III effectors (T3Es) mainly contribute to the virulence of R. solanacearum, usually by targeting immune-related proteins. Here, we clarified the effect of a novel E3 ubiquitin ligase (NEL) T3E, RipAW, from R. solanacearum on pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and further explored its action mechanism. In the susceptible host Arabidopsis thaliana, we monitored the expression of PTI marker genes, flg22-induced ROS burst, and callose deposition in RipAW- and RipAWC177A-transgenic plants. Our results demonstrated that RipAW suppressed host PTI in an NEL-dependent manner. By Split-Luciferase Complementation, Bimolecular Fluorescent Complimentary, and Co-Immunoprecipitation assays, we further showed that RipAW associated with three crucial components of the immune receptor complex, namely FLS2, XLG2, and BIK1. Furthermore, RipAW elevated the ubiquitination levels of FLS2, XLG2, and BIK1, accelerating their degradation via the 26S proteasome pathway. Additionally, co-expression of FLS2, XLG2, or BIK1 with RipAW partially but significantly restored the RipAW-suppressed ROS burst, confirming the involvement of the immune receptor complex in RipAW-regulated PTI. Overall, our results indicate that RipAW impairs host PTI by disrupting the immune receptor complex. Our findings provide new insights into the virulence mechanism of R. solanacearum.

Functionalized Hydrocarbon Belts: Synthesis, Structure and Properties.

Hydrocarbon belts have drawn great attention because of their unique structures and tantalizing properties. Although a few belts and heteroatom-doped analogs have been synthesized, belt molecules containing non-hexagonal rings remain rare. Herein we report the construction and application of unprecedented zigzag-type hydrocarbon belts which contain functionalized eight-membered rings. The synthesis features fourfold intramolecular acylation reactions of resorcin[4]arene-derived intermediates, which affords C4 -symmetric tetrabenzobelt[4]arene[4]cyclooctatrienones. Stereoselective ketone reduction with LiAlH4 and nucleophilic addition with alkynyllithiums provide the corresponding tetrahydroxylated belts. The tetraol and its methyl ether are powerful and selective hosts to form 2 : 1 and 1 : 1 complexes with cesium ion, respectively, with binding constants up to (1.71±0.33)×1011  M-2 and (1.50±0.16)×106  M-1 . In addition, enantiopure C4 -symmetric belts can emit CPL with |glum | being around 0.01.

Highly Strained Oxygen-Doped Chiral Molecular Belts of the Zigzag-Type with Strong Circularly Polarized Luminescence.

Herein we report a two-directional cyclization strategy for the synthesis of highly strained depth-expanded oxygen-doped chiral molecular belts of the zigzag-type. From the easily accessible resorcin[4]arenes, an unprecedented cyclization cascade generating fused 2,3-dihydro-1H-phenalenes has been developed to access expanded molecular belts. Stitching up the fjords through intramolecular nucleophilic aromatic substitution and ring-closing olefin metathesis reactions furnished a highly strained O-doped C2 -symmetric belt. The enantiomers of the acquired compounds exhibited excellent chiroptical properties. The calculated parallelly aligned electric (µ) and magnetic (m) transition dipole moments are translated to the high dissymmetry factor (|glum | up to 0.022). This study provides not only an appealing and useful strategy for the synthesis of strained molecular belts but also a new paradigm for the fabrication of belt-derived chiroptical materials with high CPL activities.

Effect of spermidine on ameliorating spermatogenic disorders in diabetic mice via regulating glycolysis pathway.

Diabetes mellitus (DM), a high incidence metabolic disease, is related to the impairment of male spermatogenic function. Spermidine (SPM), one of the biogenic amines, was identified from human seminal plasma and believed to have multiple pharmacological functions. However, there exists little evidence that reported SPM's effects on moderating diabetic male spermatogenic function. Thus, the objective of this study was to investigate the SPM's protective effects on testicular spermatogenic function in streptozotocin (STZ)-induced type 1 diabetic mice. Therefore, 40 mature male C57BL/6 J mice were divided into four main groups: the control group (n = 10), the diabetic group (n = 10), the 2.5 mg/kg SPM-treated diabetic group (n = 10) and the 5 mg/kg SPM-treated diabetic group (n = 10), which was given intraperitoneally for 8 weeks. The type 1 diabetic mice model was established by a single intraperitoneal injection of STZ 120 mg/kg. The results showed that, compare to the control group, the body and testis weight, as well the number of sperm were decreased, while the rate of sperm malformation was significantly increased in STZ-induced diabetic mice. Then the testicular morphology was observed, which showed that seminiferous tubule of testis were arranged in mess, the area and diameter of which was decreased, along with downregulated anti-apoptotic factor (Bcl-2) expression, and upregulated pro-apoptotic factor (Bax) expression in the testes. Furthermore, testicular genetic expression levels of Sertoli cells (SCs) markers (WT1, GATA4 and Vimentin) detected that the pathological changes aggravated observably, such as the severity of tubule degeneration increased. Compared to the saline-treated DM mice, SPM treatment markedly improved testicular function, with an increment in the body and testis weight as well as sperm count. Pro-apoptotic factor (Bax) was down-regulated expression with the up-regulated expression of Bcl-2 and suppression of apoptosis in the testes. What's more, expression of WT1, GATA4, Vimentin and the expressions of glycolytic rate-limiting enzyme genes (HK2, PKM2, LDHA) in diabetic testes were also upregulated by SPM supplement. The evidence derived from this study indicated that the SMP's positive effect on moderating spermatogenic disorder in T1DM mice's testis. This positive effect is delivered via promoting spermatogenic cell proliferation and participating in the glycolytic pathway's activation.

COP1 Mediates Dark-Induced Stomatal Closure by Suppressing FT, TSF and SOC1 Expression to Promote NO Accumulation in Arabidopsis Guard Cells.

RING-finger-type ubiquitin E3 ligase Constitutively Photomorphogenic 1 (COP1) and floral integrators such as FLOWERING LOCUS T (FT), TWIN SISTER OF FT (TSF) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) have been identified as regulators of stomatal movement. However, little is known about their roles and relationship in dark-induced stomatal closure. Here, we demonstrated that COP1 is required for dark-induced stomatal closure using cop1 mutant. The cop1 mutant closed stomata in response to exogenous nitric oxide (NO) but not hydrogen peroxide (H2O2), and H2O2 but not NO accumulated in cop1 in darkness, further indicating that COP1 acts downstream of H2O2 and upstream of NO in dark-induced stomatal closure. Expression of FT, TSF and SOC1 in wild-type (WT) plants decreased significantly with dark duration time, but this process was blocked in cop1. Furthermore, ft, tsf, and soc1 mutants accumulated NO and closed stomata faster than WT plants in response to darkness. Altogether, our results indicate that COP1 transduces H2O2 signaling, promotes NO accumulation in guard cells by suppressing FT, TSF and SOC1 expression, and consequently leads to stomatal closure in darkness. These findings add new insights into the mechanisms of dark-induced stomatal closure.

Ethylene Acts as a Local and Systemic Signal to Mediate UV-B-Induced Nitrate Reallocation to Arabidopsis Leaves and Roots via Regulating the ERFs-NRT1.8 Signaling Module.

Nitrate is the preferred nitrogen source for plants and plays an important role in plant growth and development. Under various soil stresses, plants reallocate nitrate to roots to promote stress tolerance through the ethylene-ethylene response factors (ERFs)-nitrate transporter (NRT) signaling module. As a light signal, ultraviolet B (UV-B) also stimulates the production of ethylene. However, whether UV-B regulates nitrate reallocation in plants via ethylene remains unknown. Here, we found that UV-B-induced expression of ERF1B, ORA59, ERF104, and NRT1.8 in both Arabidopsis shoots and roots as well as nitrate reallocation from hypocotyls to leaves and roots were impaired in ethylene signaling mutants for Ethylene Insensitive2 (EIN2) and EIN3. UV-B-induced NRT1.8 expression and nitrate reallocation to leaves and roots were also inhibited in the triple mutants for ERF1B, ORA59, and ERF104. Deletion of NRT1.8 impaired UV-B-induced nitrate reallocation to both leaves and roots. Furthermore, UV-B promoted ethylene release in both shoots and roots by enhancing the gene expression and enzymatic activities of ethylene biosynthetic enzymes only in shoots. These results show that ethylene acts as a local and systemic signal to mediate UV-B-induced nitrate reallocation from Arabidopsis hypocotyls to both leaves and roots via regulating the gene expression of the ERFs-NRT1.8 signaling module.

Clinical curative effect of neoadjuvant chemotherapy combined with immunotherapy and its impact on immunological function and the expression of ER, PR, HER-2 & SATB1 in HER-2-Positive breast cancer patients.

Objective: To evaluate the clinical curative effect of neoadjuvant chemotherapy combined with immunotherapy and its impact on immunological function and the expression of ER, PR, HER-2 and SATB1 in HER-2-positive breast cancer patients. Methods: The subjects of study were 80 patients with HER-2-positive breast cancer. Enrolled patients were randomly divided into two groups, with 40 cases in each group at The Fourth Affiliated Hospital of Hebei Medical University from March 2018 from March 2021. Patients in the control group were provided with neoadjuvant chemotherapy using TAC regimen merely; while those in the study group received oral administration of Apatinib Mesylate (500mg/d; three weeks a cycle) on the basis of the TAC regimen. Further comparative analysis was performed focusing on the therapeutic effect and adverse drug reaction rate of the two groups; levels of CD3+, CD4+, CD8+ and CD4+/CD8+ of T lymphocyte subsets in the two groups before and after treatment; as well as the expressions of ER, PR, HER-2 and SATB1 in the two groups before and after treatment. Results: The total response rate was 77.5% and 55% in the study group and the control group, respectively, with an obviously better outcome in the former group than that in the latter group (p=0.03). Meanwhile, the incidence of adverse reactions was 40% in the study group and 45% in the control group, without statistical difference (p=0.65). There were statistically significant differences that the levels of CD3+, CD4+, and CD4+/CD8+ in the study group were significantly higher when compared with those in the control group after treatment (CD3+, p=0.00; CD4+, p=0.02; CD4+/CD8+, p=0.00); while no evident change was observed in the level of CD8+ (p=0.88). After treatment, the positive expression rates of ER, HER-2 and SATB1 were remarkably lower in the study group than those in the control group, showing statistically significant differences (ER, HER-2, p=0.03; SATB1, p=0.02). However, there was no statistically significant difference in the positive expression rate of PR between the study group and the control group (P=0.80). Conclusions: Neoadjuvant chemotherapy combined with immunotherapy has significant effect on the treatment of HER-2-positive breast cancer patients. It can result in the significant enhancement of T lymphocyte function, obvious improvement in the negative converse rates of ER, HER-2 and SATB1, and no evident increase in the adverse drug reactions. The proposed therapeutic approach is safe, effective, and have certain clinical value.

Exploring Anion-π Interactions and Their Applications in Supramolecular Chemistry.

Noncovalent bond interactions provide primary driving forces for supramolecular processes ranging from molecular recognition to self-assembly of sophisticated abiotic and biological machineries. While hydrogen bonding and π-π interactions are arguably textbook concepts playing indispensable parts in various scientific disciplines, noncovalent anion-π interactions have been emerging as attractive forces between π systems and negatively charged species for just about two decades. At the beginning of this century, three research groups reported independently their computational studies on the interactions between anions and aromatic compounds, proposing attractive anion-π interactions. Since π systems such as aromatic rings are traditionally noted as electron rich entities, anions and π systems would be repulsive to each other if there are any interactions. In stark contrast to the acknowledged cation-π interactions, the seemingly counterintuitive noncovalent anion-π bindings invoked great interest in the following years. Although a plethora of calculations had been published, the lack of experimental evidence cast doubt on the existence of anion-π interactions between anions and charge-neutral aromatic systems.During the same time when anion-π interactions were coined, we were studying the chemistry of novel macrocyclic compounds, namely, heteracalixaromatics, and their applications in supramolecular chemistry. It has been shown that heteracalixaromatics are powerful and versatile macrocyclic hosts to bind various guest species forming interesting assembled structures and organometallic complexes. Being a member of heteracalixaromatics, tetraoxacalix[2]arene[2]triaizne adopts a 1,3-alternate conformational structure yielding a V-shaped cavity or cleft formed by two electron-deficient triazine rings. Advantageously, the macrocycle is able to self-tune the cavity sizes by altering the degrees of conjugation between the bridging oxygen atoms with their bonded aromatic rings in response to the guest species in present, rendering it an ideal tool to explore anion-π interactions. We initiated our study on anion-π interactions using tetraoxacalix[2]arene[2]triazine as a molecular tool with the primary aim to clarify experimentally the uncertainty of whether exclusive anion-π interactions exist between anions and charge-neutral aromatic rings. We provided for the first time concrete evidence substantiating the formation of typical anion-π interaction between the anions and 1,3,5-triazine ring and demonstrated subsequently the generality and binding motifs of anion-π interactions. We have then extended our study to anion-π interaction-directed or -driven anion recognition and selective sensing, transmembrane anion transport, molecular self-assembly, and stimuli-responsive aggregation systems. A number of new generation macrocycles and cages constructed from electron-deficient tetrazine and benzenetriimide segments have also been developed in the meantime, advancing the study of anion-π interactions. This Account summarizes our endeavors to explore nascent anion-π interactions and their applications in supramolecular chemistry. We hope this Account will inspire scientists from various disciplines to explore all aspects of the nascent yet fruitful research area of anion-π interactions.

A review on extracorporeal membrane oxygenation and kidney injury.

Extracorporeal membrane oxygenation (ECMO) is inevitable external life support in case of cardiac and respiratory failure since the 1970s. Acute kidney injury (AKI) and the requirement of renal replacement therapy (RRT) is a potential risk among these patients. This review aims to give an overview of the risk of AKI, RRT, and associated mortality among the patients who received ECMO for any of its indications. PubMed database was searched to find the relevant literature and the reference list of included studies was also searched for additional studies. The incidence of AKI ranged from 30% to 78% and RRT from 47% to 60% in ECMO patients. The pathophysiology of AKI in ECMO is multifactorial, and includes ischaemia, RBCs breakdown, comorbidity, conversion of zymogen form of pro-inflammatory mediators, structural alteration of the kidney, coadministration of nephrotoxic drugs, coagulation abnormality, and oxidative stress. ECMO was associated with the higher incidence of renal abnormalities, AKI, requirement of RRT, and associated mortality. Patients who underwent RRT had improved renal function and reduced overall mortality compared to the non-RRT group among the ECMO patients. Currently, there is no consensus evidence to support the superior use of the inline hemofilter system over continuous renal replacement therapy among patients who had AKI during ECMO.

CD4+ T cells apoptosis and conversion of Th1/Th2-type cytokines promote the progress of sporotrichosis.

Sporotrichosis is a fungal disease of the human and other mammals, caused by a complex of Sporothrix schenckii. The disease follows the traumatic inoculation to lead to fixed lesions, regional lymphangitic lesions, or even disseminated lesions including internal involvement, which depends on host immunological status and strain virulence. In this work, we observed the role of CD4+ T cells apoptosis and conversion of Th1/Th2-type cytokines in the cellular immunity regulation on mice model sporotrichosis. The experiments showed that there was more CD4+ T cells apoptosis, by endogenous apoptosis signaling pathway (P < .05), and more conversions of Th1/Th2-type cytokines in more severe and longer duration groups (P < .05). Meanwhile, the trends of the conversions of Th1/Th2-type cytokines were almost consistent with the CD4 + T cell's apoptosis in the corresponding groups. These findings suggest that CD4+ T cells apoptosis and conversion of Th1/Th2-type cytokines are contributing to promoting the progress of sporotrichosis.

Overexpression of CENPF is associated with progression and poor prognosis of lung adenocarcinoma.

Background and aim: The molecular signatures of lung adenocarcinoma (LUAD) are not well understood. Centromere protein F (CENPF) has been shown to promote oncogenesis in many cancers; however, its role in LUAD has not been illustrated. We explored the role of CENPF in LUAD. Methods: CENPF expression level was investigated in public online database firstly, the prognosis of CENPF in LUAD were also assessed by Kaplan-Meier analysis. Then quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed using 13 matched pairs of clinical LUAD tissue samples. Subsequently, the impact of CENPF expression on cell proliferation, cell cycle, apoptosis, colony formation was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometric analysis and colony formation assay, respectively. Finally, experimental xenograft lung cancer model of nude mice armpit of right forelimb to determine the effect of CENPF on LUAD tumorigenesis. Results: CENPF mRNA expression was significantly elevated in LUAD tissues compared with adjacent non-tumor lung tissues in Gene Expression Profiling Interactive Analysis (GEPIA) (P < 0.001). Up-regulated CENPF was remarkably positively associated with pathological stage, relapse free survival (RFS) as well as overall survival (OS) of LUAD patients. Besides, CENPF knockdown greatly suppressed A549 cell proliferation, induced S phase arrest, promoted apoptosis and decreased colony numbers of LUAD cells. Furthermore, knockdown of CENPF significantly inhibited the tumor growth of the LUAD cells in an experimental xenograft lung cancer model of nude mice armpit of right forelimb. Conclusion: Taken together, these results demonstrated that CENPF may serve as a potential biomarker of prognostic relevance and a potential therapeutic target for LUAD.

Hydrocarbon Belts with Truncated Cone Structures.

We report in this communication the synthesis, structure, and application of a novel type of hydrocarbon belts. Starting from inexpensive and easily available resorcin[n]arenes, a closing-all-fjords strategy featuring exhaustive triflation of phenolic hydroxyl groups followed by consecutively the transition-metal-catalyzed vinylation and intramolecular olefin metathesis allowed facile construction of belt[n]arene[n]tropilidenes (n = 4, 6), which adopt double-stranded macrocyclic belt structures with unique truncated cone cavities. Selective hydrogenation reactions of olefin and benzene subunits led to diverse hydrocarbon belts with varied structures. Moreover, the resulting molecular belts acted as synthetic host materials to include selectively small molecules such as nitromethane and p-xylene.

Toward the Synthesis of a Highly Strained Hydrocarbon Belt.

Hydrocarbon belts including fully conjugated beltarenes and their (partially) saturated analogs have fascinated chemists for decades due to their aesthetic structures, tantalizing properties, and potential applications in supramolecular chemistry and carbon nanoscience and nanotechnology. However, synthesis of hydrocarbon belts still remains a formidable challenge. We report in this communication a general approach to hydrocarbon belts and their derivatives. Closing up all four fjords of resorcin[4]arene derivatives through multiple intramolecular Friedel-Crafts alkylation reactions in an operationally simple one-pot reaction manner enabled efficient construction of octohydrobelt[8]arenes. Synthesis of belt[8]arene from DDQ-oxidized aromatization of octohydrobelt[8]arene under different conditions resulted in aromatization and simultaneous [4 + 2] cycloaddition reactions with DDQ or TCNE to produce selectively tetrahydrobelt[8]arene-DDQ2, tetrahydrobelt[8]arene-TCNE2, and belt[8]arene-DDQ4 adducts. Formation of belt[8]arene, a fully conjugated hydrocarbon belt, was observed from retro-Diels-Alder reaction of a belt[8]arene-DDQ4 adduct with laser irradiation under MALDI conditions. The new and practical synthetic method established would open an avenue to create belt-shaped molecules from easily available starting materials.