Tumor Microenvironment Heterogeneity, Potential Therapeutic Avenues, and Emerging Therapies.

OBJECTIVE: This review describes the comprehensive portrait of tumor microenvironment (TME). Additionally, we provided a panoramic perspective on the transformation and functions of the diverse constituents in TME, and the underlying mechanisms of drug resistance, beginning with the immune cells and metabolic dynamics within TME. Lastly, we summarized the most auspicious potential therapeutic strategies. RESULTS: TME is a unique realm crafted by malignant cells to withstand the onslaught of endogenous and exogenous therapies. Recent research has revealed many small-molecule immunotherapies exhibiting auspicious outcomes in preclinical investigations. Furthermore, some pro-immune mechanisms have emerged as a potential avenue. With the advent of nanosystems and precision targeting, targeted therapy has now transcended the "comfort zone" erected by cancer cells within TME. CONCLUSION: The ceaseless metamorphosis of TME fosters the intransigent resilience and proliferation of tumors. However, existing therapies have yet to surmount the formidable obstacles posed by TME. Therefore, scientists should investigate potential avenues for therapeutic intervention and design innovative pharmacological and clinical technologies.

A Network Analysis of Brief Measure of Perceived Courtesy and Affiliate Stigma During COVID-19 in Hubei China.

PURPOSE: The current study aims to test perceived affiliate and courtesy stigma in Hubei province China during the early periods of COVID-19 by using network analysis. METHOD: In this study, 4,591 participants (3,034 female, mean age = 26.64) from the Hubei Province of China were recruited to conduct network analysis. RESULTS: The network analysis found network connections between Estranged - Blamed, Shamed - No Strong Point, and Rejected - Plague were the strongest. The most important stigma features (nodes) of COVID-19 (i.e. Plague, No Strong Point, Discriminated, and Disgusting). DISCUSSION AND CONCLUSIONS: This study uncovered the most central features of perceived affiliate and courtesy stigma on COVID-19, proposing these features (and associations between features) could be prioritized for anti-stigma interventions for the COVID-19 pandemic.

Lung carcinoma with small intestinal metastases and gastrointestinal bleeding: A rare case report.

The occurrence of small intestinal metastases from primary lung cancer is rare. This report documents the case of a 57-year-old male patient initially diagnosed with non-metastatic lung adenocarcinoma, who presented with abdominal pain 6 months later. Postoperative pathological analysis confirmed the final diagnosis to be small intestinal metastasis from primary lung cancer. Thoracoscopic surgery and systemic chemotherapy were the preferred treatment options. However, the lung tumor spread to the small intestine, causing intestinal obstruction. As the patient could not tolerate anti-tumor therapy, only symptomatic treatment was provided. The patient experienced massive gastrointestinal bleeding and died the next day. Although small intestinal metastasis from lung cancer is rare and difficult to diagnose accurately, it should be considered when encountering a patient with lung cancer exhibiting abdominal symptoms and associated imaging findings. At this point, a pathological diagnosis should be performed immediately to determine the nature and source of the tumor. Furthermore, individualized treatment should be conducted in strict accordance with oncology guidelines. Of note, early detection and treatment are critical to ensure favorable outcomes.

PlaneSeg: Building a Plug-In for Boosting Planar Region Segmentation.

Existing methods in planar region segmentation suffer the problems of vague boundaries and failure to detect small-sized regions. To address these, this study presents an end-to-end framework, named PlaneSeg, which can be easily integrated into various plane segmentation models. Specifically, PlaneSeg contains three modules, namely, the edge feature extraction module, the multiscale module, and the resolution-adaptation module. First, the edge feature extraction module produces edge-aware feature maps for finer segmentation boundaries. The learned edge information acts as a constraint to mitigate inaccurate boundaries. Second, the multiscale module combines feature maps of different layers to harvest spatial and semantic information from planar objects. The multiformity of object information can help recognize small-sized objects to produce more accurate segmentation results. Third, the resolution-adaptation module fuses the feature maps produced by the two aforementioned modules. For this module, a pairwise feature fusion is adopted to resample the dropped pixels and extract more detailed features. Extensive experiments demonstrate that PlaneSeg outperforms other state-of-the-art approaches on three downstream tasks, including plane segmentation, 3-D plane reconstruction, and depth prediction. Code is available at https://github.com/nku-zhichengzhang/PlaneSeg.

Systematic analysis of the oncogenic role of FAM83D across cancers based on data mining.

Family with sequence similarity of 83D (FAM83D) is overexpressed in various cancers. However, no pan-cancer analysis is presently available. In the present study, we used a bioinformatics analysis to explore the diagnostic and prognostic value of FAM83D expression levels in human cancers. The GEPIA 2, TIMER 2.0, ENCORI, and DriverDBV3 databases were used to evaluate FAM83D expression levels. The potential prognostic value of FAM83D expression was analyzed using the GEPIA 2, UALCAN, and TISIB databases. The driver gene and promoter methylation levels regarding FAM83D were evaluated using the TIMER 2.0 and UALCAN databases. To further analyze interactive networks for FAM83D, FAM83D-binding proteins and related genes were determined using STRING and Gene MANIA analytic tools. Highly expressed FAM83D could be associated with mutated TP53 and promoter DNA methylation. Relative network analysis suggested that FAM83D was mainly involved in the progesterone-mediated oocyte maturation pathway, cell cycle regulation, and several other signaling pathways. Therefore, the differential expression of FAM83D could serve as a diagnostic and prognostic biomarker for various cancers. Our study revealed useful information about the differential expression of FAM83D, prognostic values, and potential functional networks in a variety of cancers, providing valuable substantive and methodological information to explore the underlying mechanisms.Abbreviations: BP: Biological processes; CC: Cellular components; DAVID: Database for Annotation, Visualization, and Integrated Discovery; DFS: Disease-free survival; ENCORI: Encyclopedia of RNA Interactomes; FAM83: Family with sequence similarity 83; FAM83D: Family with sequence similarity of 83D; GEO: Gene Expression Omnibus; GEPIAx2: Gene Expression Profiling Interactive Analysis 2; GO: Gene Ontology; GTEx: Genotype-Tissue Expression; KEGG: Kyoto Encyclopedia of Genes and Genomes; KIRC: Kidney renal clear cell carcinoma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; MF: Molecular functions miRNA: microRNA; OS: Overall survival; PAAD: Pancreatic adenocarcinoma; PPI: Protein - protein interaction; RNA-seq: RNA-sequencing; TCGA: The Cancer Genome Atlas; TIMER 2.0: Tumor Immune Estimation Resource 2.0; UALCAN: University of Alabama at Birmingham Cancer; UCEC: Uterine corpus endometrial carcinoma.

Are risk-need-responsivity principles golden? A meta-analysis of randomized controlled trials of community correction programs.

Objectives: Using meta-analysis to determine the effect size of the recidivism rate of participants in community correction programs that are conducted entirely in community settings. Methods: Following the Preferred Reported Items for Systematic Reviews and Meta-analyses (PRISMA), 25 qualified studies contributed 35 independent effect sizes. Results: Full participation in a program significantly reduced the recidivism rate. Participant age was a significant moderator of heterogeneity. Those aged over 18 have lower recidivism rates. Interventions that fully follow the Risk-Need-Responsivity (RNR) design principles achieved similar results to those that did not. Recidivism rates increase more than 12 months after the program ends. Conclusions: The effectiveness of community correctional programs varies depending on the participant's age. The RNR principles are not golden. The above factors should be carefully considered when conducting intervention design in the future. Results should be interpreted with caution due to the literature's high heterogeneity and low quality. Supplementary Information: The online version contains supplementary material available at 10.1007/s11292-022-09550-w.

Effects of Solution Treatment on Damping Capacities of Binary Mg-X (X = Ga and Er) Alloys.

Designing new materials for vibration and noise reduction that are lightweight is of great significance for industrial development. Magnesium (Mg) alloy is considered one of the best damping metal structural materials because of its low density, high specific strength, good energy storage characteristics and rich resources. Solution atoms have an important effect on the damping capacities of Mg alloys, but the relevant laws have not been completely clarified. In this work, two kinds of alloying elements (Ga and Er) with various atomic sizes were selected to study the metallographic structure and damping capacities of binary Mg-X (X = Ga and Er) alloys in the as-cast and solid solution states, respectively. Solution treatment can improve the damping capacities of binary Mg-X (X = Ga and Er) alloys, and the damping mechanisms of the two solid solution alloys are consistent with the G-L damping mechanism. The influence of alloy elements with different atomic sizes on damping capacities is also different. This influence is due to the various radii of solute atoms and Mg atoms which can result in different degrees of lattice distortion. This work provides a research basis for development and design of high-performance damping Mg alloy materials.

In vitro investigation of mammalian early embryonic development.

Mammalian embryonic development starts from a fertilized egg, which cleaves to form morula and blastocyst. At the same time, the early embryo is transported from the fallopian tube to the uterus for implantation. After implantation, the embryo undergoes gastrulation and forms a gastrula, further developing a new individual. The development of embryo in the uterus causes the difficulties in sampling and observation, hindering the understanding of mammalian embryonic development. Therefore, it is necessary to develop the technology to overcome the barrier of in vivo embryonic development. In December 2021, "Embryo 'husbandry' opens windows into early development" was selected as one of Science's 2021 breakthroughs. This review focuses on the achievements of in vitro mammalian embryos and discusses their limitations and the future applications for the investigation of mammalian embryonic development and human related diseases.

Inorganic Ferrocene Analogue [Fe(P4)2]2.

Inorganic metallocene derivatives containing only cyclo-Pn ligands have been targeted for more than 20 years, but their syntheses have never been achieved by pursuing the conventional route of using P4 phosphorus except for the generation of [Ti(η5-P5)2]2-. Herein, we report a facile one-step method for the synthesis of the homoleptic iron complex [Fe(P4)2]2- by the Zintl-phase-type precursor KP. 31P NMR analyses indicate that upon dissolving the KP phase in ethylenediamine P42- was generated only in the presence of 2,2,2-crypt. The amounts of cation-sequestering agents, the type of iron precursor, and their consuming ratio have a decisive impact on the yield of [Fe(P4)2]2-. Both the FeII and the FeIII precursors can oxidize P42- to give a concomitant product [(P7)Fe(P4)]3-, which can be partially inhibited by the addition of potassium to produce relatively pure crystalline [K(2,2,2-crypt)]2[Fe(P4)2].

La(OH)3 nano-rods/polyacrylonitrile nanofibers: fabrication, characterization and application for phosphate removal.

In this study, an excellent phosphate adsorbent was prepared for removing phosphate to an extremely low concentration. The La(OH)3 nano-rods stabilizing in polyacrylonitrile (PAN) nanofibers (PLNFs) were prepared by electrospinning and a subsequent in situ precipitation. PAN nanofibers were employed as the matrix of the composite nanofibers, where the well-dispersed La(OH)3 nano-rods were encapsulated as the active species for highly efficient phosphate capture owing to the strong binding between phosphate and lanthanum. On account of the nano-structure, the maximum phosphate adsorption capacity was 151.98 mg P/g (La), much higher than the result of La(OH)3 nano-crystal, produced by precipitation without PAN or any organic surfactants. Moreover, the PLNFs could remove phosphate (2 mg P/L) to an extremely low concentration within 20 min, which could lead to a nutrient deficient condition to protect water quality and ecosystem. The optimization of PLNFs design was implemented through parameter adjustment of electrospinning. Lanthanum salt content, humidity, concentration of solution and applied voltage were chosen to analyze the influences on the composition, diameter and morphology of the nanofibers, giving the result that the most effective adsorbent was the PLNFs with spider-web-like nano-structures.

A sandwich-type cluster containing Ge@Pd3 planar fragment flanked by aromatic nonagermanide caps.

Sandwich-type clusters with the planar fragment containing a heterometallic sheet have remained elusive. In this work, we introduce the [K(2,2,2-crypt)]4{(Ge9)2[η6-Ge(PdPPh3)3]} complex that contains a heterometallic sandwich fragment. The title compound is structurally characterized by means of single-crystal X-ray diffraction, which reveals the presence of an unusual heteroatomic metal planar fragment Ge@Pd3. The planar fragment contains a rare formal zerovalent germanium core and a peculiar bonding mode of sp2-Ge@(PdPPh3)3 trigonal planar structure, whereas the nonagermanide fragments act as capping ligands. The chemical bonding pattern of the planar fragment consists of three 2c-2e Pd-Ge σ-bonds attaching Pd atoms to the core Ge atom, while the binding between the planar fragment and the aromatic Ge9 ligands is provided by six 2c-2e Pd-Ge σ-bonds and two delocalized 4c-2e σ-bonds. The synthesized cluster represents a rare example of a sandwich compound with the heteroatomic metal planar fragment and inorganic aromatic capping ligands.

σ-Aromaticity-Induced Stabilization of Heterometallic Supertetrahedral Clusters [Zn6 Ge16 ]4- and [Cd6 Ge16 ]4.

In this work, the largest heterometallic supertetrahedral clusters, [Zn6 Ge16 ]4- and [Cd6 Ge16 ]4- , were directly self-assembled through highly-charged [Ge4 ]4- units and transition metal cations, in which 3-center-2-electron σ bonding in Ge2 Zn or Ge2 Cd triangles plays a vital role in the stabilization of the whole structure. The cluster structures have an open framework with a large central cavity of diameter 4.6 Šfor Zn and 5.0 Šfor Cd, respectively. Time-dependent HRESI-MS spectra show that the larger clusters grow from smaller components with a single [Ge4 ]4- and ZnMes2 units. Calculations performed at the DFT level indicate a very large HOMO-LUMO energy gap in [M6 Ge16 ]4- (2.22 eV), suggesting high kinetic stability that may offer opportunities in materials science. These observations offer a new strategy for the assembly of heterometallic clusters with high symmetry.

All-metal σ-antiaromaticity in dimeric cluster anion {[CuGe9Mes]2}4.

In this work, we report a dimeric cluster anion, {[CuGe9Mes]2}4-, which was isolated as the [K(2,2,2-crypt)]+ salt and characterized by using single-crystal X-ray diffraction and ESI mass spectroscopy. The title cluster represents the first locally σ-antiaromatic compound in the solid state, as well as the first heteroatomic antiaromatic compound.

Mitochondrial Ca2+ Overload Leads to Mitochondrial Oxidative Stress and Delayed Meiotic Resumption in Mouse Oocytes.

Overweight or obese women seeking pregnancy is becoming increasingly common. Human maternal obesity gives rise to detrimental effects during reproduction. Emerging evidence has shown that these abnormities are likely attributed to oocyte quality. Oxidative stress induces poor oocyte conditions, but whether mitochondrial calcium homeostasis plays a key role in oocyte status remains unresolved. Here, we established a mitochondrial Ca2+ overload model in mouse oocytes. Knockdown gatekeepers of the mitochondrial Ca2+ uniporters Micu1 and Micu2 as well as the mitochondrial sodium calcium exchanger NCLX in oocytes both increased oocytes mitochondrial Ca2+ concentration. The overload of mitochondria Ca2+ in oocytes impaired mitochondrial function, leaded to oxidative stress, and changed protein kinase A (PKA) signaling associated gene expression as well as delayed meiotic resumption. Using this model, we aimed to determine the mechanism of delayed meiosis caused by mitochondrial Ca2+ overload, and whether oocyte-specific inhibition of mitochondrial Ca2+ influx could improve the reproductive abnormalities seen within obesity. Germinal vesicle breakdown stage (GVBD) and extrusion of first polar body (PB1) are two indicators of meiosis maturation. As expected, the percentage of oocytes that successfully progress to the germinal vesicle breakdown stage and extrude the first polar body during in vitro culture was increased significantly, and the expression of PKA signaling genes and mitochondrial function recovered after appropriate mitochondrial Ca2+ regulation. Additionally, some indicators of mitochondrial performance-such as adenosine triphosphate (ATP) and reactive oxygen species (ROS) levels and mitochondrial membrane potential-recovered to normal. These results suggest that the regulation of mitochondrial Ca2+ uptake in mouse oocytes has a significant role during oocyte maturation as well as PKA signaling and that proper mitochondrial Ca2+ reductions in obese oocytes can recover mitochondrial performance and improve obesity-associated oocyte quality.

A fast and highly selective Congo red adsorption material based on a cadmium-phosphonate network.

In this work, a cadmium-phosphonate network was prepared based on a tetrahedral shaped tetraphosphonic acid linker. The resulting three-dimensional compound Cd4(H4L)2(phen)2(H2O)4 (1) exhibited a rapid and efficient adsorption of Congo red (CR) dye, the adsorption capacity of which reached 684 mg g-1. Furthermore, this adsorbent showed excellent structural stability and adsorptive recyclability after three times of adsorption and desorption. The absorption kinetics fitted well with the pseudo-second-order kinetic model, revealing that the adsorption of the cadmium-phosphonate compound undergoes a chemical process, where hydrogen bonding between the amide groups (from CR) and the uncoordinated phosphonate oxygen atoms of the compound plays a pivotal role.

Structural isomerism in the [(Ni@Sn9)In(Ni@Sn9)]5- Zintl ion.

A new Zintl cluster, [(Ni@Sn9)In(Ni@Sn9)]5-, has been isolated in two distinct isomeric forms, one where both Ni@Sn9 units are coordinated to the bridging In atom in an η3- mode, the other where one is η3- and the other η4-. Density functional theory indicates that the energetic separation between these two structures is minimal, suggesting that crystal packing plays a decisive role in the structural chemistry. A comparison of the electronic structure of [(Ni@Sn9)In(Ni@Sn9)]5- with [(Ni@Ge9)Ni(Ni@Ge9)]4-, which has four fewer valence electrons, sheds some light on possible mechanisms that lead to the fusion of cluster fragments.

Microarray gene profiling analysis of glioblastoma cell line U87 reveals suppression of the FANCD2/Fanconi anemia pathway by the combination of Y15 and temozolomide.

INTRODUCTION: A recent study showed that a combination of Y15 (a FAK autophosphorylation inhibitor) with temozolomide (TMZ) treatment was effective in glioblastoma (GBM) therapy. In this study, we further investigated the pathways and genes that are differentially expressed in Y15 and TMZ treated U87 cells via bioinformatics analysis. MATERIAL AND METHODS: The microarray gene profiling analysis screened out genes with differential expression in U87 cells treated with TMZ and Y15. Gene set enrichment analysis (GSEA) identified the key GO terms and KEGG pathways in TMZ + Y15 treated U87 cells. The functional partner genes of TMZ were predicted by the STICH database. FANCD2 expression in U87 cells was detected by qRT-PCR. MTT assay and colony formation assay were conducted for cell viability detection, and flow cytometry was performed for cell apoptosis detection. Western blot was conducted to determine the expression levels of the downstream proteins of the Fanconi anemia (FA) pathway, FAN1 and BRCA2. RESULTS: The FA pathway was suppressed in U87 cells after treatment with TMZ and Y15. Genes involved in this pathway, including FANCD2, were also down-regulated. FANCD2 knockdown could restrain viability and promote apoptosis of U87 cells, as well as enhancing the inhibitory effect of TMZ + Y15 treatment. FANCD2 could regulate the FA pathway as the protein expression levels of FAN1 and BRCA2 were modulated by FANCD2. CONCLUSIONS: The FA pathway and FANCD2 are down-regulated in U87 cells treated with TMZ and Y15. FANCD2 down-regulation by TMZ + Y15 treatment suppressed growth of U87 cells through inhibiting the FA pathway.

Predictive value of P-selectin and endothelin-1 for vascular restenosis after interventional procedures for peripheral artery disease.

Peripheral artery disease (PAD) is caused by the building up of plaques in the arteries that carry blood to the lower limbs. The present study aimed to assess the predictive value of the plasma levels of P-selectin (Ps) or endothelin-1 (ET-1) regarding the occurrence of vascular restenosis after endovascular therapy for PAD. Patients with or without vascular restenosis confirmed by computed tomography angiography after endovascular therapy between March and December 2015 (n=20 per group) were enrolled. The serum levels of Ps and ET-1 prior to the operation and at 1 h, as well as 1, 2 and 3 weeks after the operation were compared between the two groups. At 1 h after the operation, the serum levels of Ps and ET-1 were significantly increased as compared with the pre-operative levels (P<0.05). The serum levels of Ps and ET-1 at 1 h, as well as 1, 2 and 3 weeks after the operation in the restenosis group were significantly higher as compared with those in the non-stenosis group (P<0.05). However, for the non-stenosis group, the serum levels of Ps and ET-1 at 1, 2 and 3 weeks after the operation did not significantly differ from the pre-operative levels (P>0.05). The diagnostic sensitivity and specificity of the serum ET-1 levels at 1 h after the operation for predicting post-operative restenosis in PAD patients with a cut-off of 0.1089 pg/ml were 85 and 85%, respectively. In conclusion, the serum levels of Ps and ET-1 have a high predictive value for post-operative vascular restenosis after endovascular therapy for PAD patients.

Polar-Group Activated Isospecific Coordination Polymerization of ortho-Methoxystyrene: Effects of Central Metals and Ligands.

Stereoselective polymerization of polar vinyl monomers has been a long-standing challenge because the employed transition-metal catalysts are easily poisoned by polar groups of monomers. In this contribution, a series of ß-diketiminato rare-earth metal complexes 1-5 (L1-5 Ln(CH2 SiMe3 )2 (THF)n , Ln=Gd-Lu, Y, and Sc) were successfully synthesized. In combination with AliBu3 and [Ph3 C][B(C6 F5 )4 ], complexes 1 c(Tb)-1 g(Tm) exhibited high activities and excellent isoselectivities for the polymerization of ortho-methoxystyrene (oMOS), in which, the polar methoxy group of oMOS did not poison but activated the polymerization through σ-π chelation to the active species together with the vinyl group. Moreover, the large Gd-attached precursor 1 b showed a higher activity, albeit with a slightly decreased isoselectivity. The small Sc-attached precursor 1 i was completely inert. Meanwhile, the spatial steric arrangement and the coordination mode of the ß-diketiminato ligand could clearly affect and even block oMOS polymerization. This work sheds new light on the coordination polymerization of polar monomers.

Mechanism and Effect of Polar Styrenes on Scandium-Catalyzed Copolymerization with Ethylene.

Copolymerization of ethylene (E) and polar vinyl monomers remains a problem because E propagation is hindered. Herein, for the first time, we report the copolymerization of E and polar styrenes (SR ) by using an oxophilic scandium catalyst that exhibits higher turnover frequencies than both E and SR homopolymerizations when R is an electron-withdrawing group. This positive comonomer effect was elucidated through computing reaction profiles of E/SF copolymerization at the DFT (B3PW91) level of theory. It reveals that the secondary interaction between Sc3+ and phenyl of the last and penultimate inserted SF units leads to a decrease of the E insertion barrier, because the electron-withdrawing substituent enhances the electrophilicity of Sc3+ by an inductive effect mediated by the secondary interaction. After three consecutive insertions of the E units, the secondary interaction is lost and the SF insertion is kinetically preferred over the E insertion. This process is in line with the NMR spectrum analyses which show that the resultant copolymers mainly contain SR (E)x SR sequences where x≤3.