The genomes of seven economic Caesalpinioideae trees provide insights into polyploidization history and secondary metabolite biosynthesis.

The Caesalpinioideae subfamily contains many well-known trees that are important for the sustainability of the economy and human health, but the lack of genomic resources hindered the breeding and utilization of these plants. Here, we present chromosome-level reference genomes for two food and industrial trees Gleditsia sinensis (921 Mb) and Biancaea sappan (872 Mb), three shade and ornamental trees Albizia julibrissin (705 Mb), Delonix regia (580 Mb) and Acacia confusa (566 Mb), as well as two pioneer and hedgerow trees Leucaena leucocephala (1,338 Mb) and Mimosa bimucronata (641 Mb). Phylogeny inference showed that the mimosoid clade has a much higher evolution rate than the other clades of Caesalpinioideae. Macrosynteny comparison showed that the fusion and broken of an unstable chromosome was responsible for the difference in the basic chromosome number 13 and 14 for Caesalpinioideae. After the ancient whole genome duplication shared by all Caesalpinioideae species (CWGD, ∼72.0 MYA), we found two recent successive WGD events LWGD-1 (16.2-19.5 MYA) and LWGD-2 (7.1-9.5 MYA) in L. leucocephala. Then, ∼40% gene loss and genome size contraction occurred during the diploidization process in L. leucocephala. For the secondary metabolites, we identified all the gene copies involved in mimosine metabolism for these species and revealed that the abundance of mimosine biosynthesis genes in L. leucocephala largely explains its high mimosine production. Moreover, we identified all the potential genes involved in triterpenoid saponin biosynthesis in G. sinensis, which is more complete than the previous transcriptome-derived unigenes. Our analyzing results and the genomic resources will facilitate the biological studies of Caesalpinioideae and promote the utilization of valuable secondary metabolites.

A molecular sheaf: doubly threaded [6]rotaxane.

We report that the use of a hydrogen-bonded pyrimidine-macrocycle complex can efficiently facilitate the threading of two bispyridinium ethylenes into four rings, as evidenced by X-ray crystallography of its precursor, offering a rare example of a doubly threaded [6]rotaxane in 91% yield. The unusual architecture is found to be stable with no dethreading despite the large ring size of the macrocycle with respect to the stopper.

Generation and characterization of the iPS cell line (SYSUSHi001-A) derived from the peripheral blood mononuclear cells (PBMCs) of a 33-year-old patient with acute myeloid leukemia (AML).

We successfully developed an induced pluripotent stem cell (iPSC) line, SYSUSHi001-A, from the peripheral blood mononuclear cells (PBMC) of a patient with Acute Myeloid Leukemia, harboring two genetic mutations (XPO1: c.591-4_591-3dupTT; PALB2: c.3296C > T; p.T1099M). This iPSC line was facilitated through the use of episomal plasmids encoding OCT4, SOX2, KLF4, L-MYC, and human miR-302. The SYSUSHi001-A iPSC line exhibited characteristic embryonic stem cell-like morphology, maintained the XPO1 and PALB2 mutations, expressed key pluripotency markers, preserved a normal karyotype (46, XY), and demonstrated the ability to differentiate into cells from all three germ layers in vitro.

Pillar[5]arene-segregated ion pairs for enhanced cycloaddition of epoxides with CO2.

A supramolecular approach using a polyviologen-pillar[5]arene complex as segregated ion pairs was shown to be highly efficient for the conversion of CO2 with epoxides into cyclic carbonates without the need for metals or solvents. The enhanced catalytic performance was achieved by cooperative ion pair segregation and CO2 fixation.

Construction of Oligorotaxanes with Hydrogen-Bonded Aramide Macrocycles through Threaded Host-Guest Complexation.

The development of efficient and selective organic synthetic approaches for complex molecules has garnered significant attention due to the need for precise control over molecular structures and functions. Rotaxanes, a type of mechanically interlocked molecules (MIMs), have shown promising applications in various fields including sensing, catalysis, and material science. However, the highly selective synthesis of oligo[n]rotaxanes (mostly n≥3) through controlling host-guest complexation and supramolecular threading assembly process still remains an ongoing challenge. In particular, the utilization of two-dimensional (2D) macrocycles with structural shape-persistency for the synthesis of oligo[n]rotaxanes is rare. In this concept, research on cooperatively threaded host-guest complexation with hydrogen-bonded (H-bonded) aramide macrocycles and selective synthetic protocols of oligo[n]rotaxanes has been summarized. The high efficiency and selectivity in synthesis are ascribed to the synergistic interplay of multiple non-covalent bonding interactions such as hydrogen bonding and intermolecular π-π stacking of macrocycles within the unique supramolecular structure of threaded host-guest complexes. This review focuses on the latest progress in the concepts, synthesis, and properties of H-bonded aramide macrocycle-based oligorotaxanes, and presents an in-depth outlook on challenges in this emerging field.

Glutathione promotes the synergistic effects of venetoclax and azacytidine against myelodysplastic syndrome­refractory anemia by regulating the cell cycle.

Azacitidine is a DNA methyltransferase inhibitor that has been used as a singular agent for the treatment of myelodysplastic syndrome-refractory anemia with excess blast-1 and -2 (MDS-RAEB I/II). However, recurrence and overall response rates following this treatment remain unsatisfactory. The combination of azacitidine and venetoclax has been used for the clinical treatment of a variety of hematological diseases due to the synergistic killing effect of the two drugs. Venetoclax is a BCL-2 inhibitor that can inhibit mitochondrial metabolism. In addition, azacitidine has been shown to reduce the levels of myeloid cell leukemia 1 (MCL-1) in acute myeloid leukemia cells. MCL-1 is an anti-apoptotic protein and a potential source of resistance to venetoclax. However, the mechanism underlying the effects of combined venetoclax and azacitidine treatment remains to be fully elucidated. In the present study, the molecular mechanism underlying the impact of venetoclax on the efficacy of azacitidine was investigated by examining its effects on cell cycle progression. SKM-1 cell lines were treated in vitro with 0-2 µM venetoclax and 0-4 µM azacytidine. After 24, 48 and 72 h of treatment, the impact of the drugs on the cell cycle was assessed by flow cytometry. Following drug treatment, changes in cellular glutamine metabolism pathways was analyzed using western blotting (ATF4, CHOP, ASCT2, IDH2 and RB), quantitative PCR (ASCT2 and IDH2), liquid chromatography-mass spectrometry (α-KG, succinate and glutathione) and ELISA (glutamine and glutaminase). Venetoclax was found to inhibit mitochondrial activity though the alanine-serine-cysteine transporter 2 (ASCT2) pathway, which decreased glutamine uptake. Furthermore, venetoclax partially antagonized the action of azacitidine through this ASCT2 pathway, which was reversed by glutathione (GSH) treatment. These results suggest that GSH treatment can potentiate the synergistic therapeutic effects of venetoclax and azacitidine combined treatment on a myelodysplastic syndrome-refractory anemia cell line at lower concentrations.

Peptidomic analysis of follicular fluid in patients with polycystic ovarian syndrome.

Objective: The aim of this study was to analyze and compare the differential expression of peptides within the follicular fluid of polycystic ovary syndrome (PCOS) patients versus normal women by using peptidomics techniques. The underlying mechanisms involved in PCOS pathogenesis will be explored, together with screening and identification of potential functional peptides via bioinformatics analysis. Materials and methods: A total of 12 patients who underwent in vitro fertilization and embryo transfer (IVF-ET) at the Reproductive Medicine Center of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from 1 September 2022 to 1 November 2022 were included in this study. The follicular fluid of PCOS patients (n = 6) and normal women (n = 6) were collected. The presence and concentration differences of various peptides were detected by the LC-MS/MS method. GO and KEGG analysis were performed on the precursor proteins of the differentially-expressed peptides, and protein network interaction analysis was carried out to identify functionally-relevant peptides among the various peptides. Results: A variety of peptides within the follicular fluid of PCOS versus normal patients were detected by peptidomics techniques. Altogether, 843 upregulated peptides and 236 downregulated peptides were detected (absolute fold change ≥2 and p < 0.05). Of these, 718 (718 = 488 + 230) peptides were only detected in the PCOS group, while 205 (205 = 174 + 31) were only detected in the control group. Gene Ontology enrichment and pathway analysis were performed to characterize peptides through their precursor proteins. We identified 18 peptides from 7 precursor proteins associated with PCOS, and 4 peptide sequences were located in the functional domains of their corresponding precursor proteins. Conclusion: In this study, differences in the follicular development of PCOS versus normal patients were revealed from the polypeptidomics of follicular development, which thus provided new insights for future studies on the pathological mechanisms of PCOS development.

Comparison of diagnosis-related group based reimbursement and case-mix index within hospitalized patients before and after modified malnutrition diagnosis.

BACKGROUND AND OBJECTIVES: Lack of professional and accurate diagnosis of malnutrition led to a reduction in Diagnosis Related Group (DRG) payment and a decrease in Case-Mix Index (CMI). The aim of this study was to explore the effects of adding a proper nutritional diagnosis and modifying complication groups on DRG payment and CMI. METHODS AND STUDY DESIGN: Retrospective analysis was performed on patients ad-mitted to the hospital from January to June 2022 who had received a nutritional assessment. Patients were diagnosed as well-nourished, mild malnutrition, moderate malnutrition or severe malnutrition according to patient-generated subjective global assessment (PG-SGA) scores within 24 hours of admission. CMI and DRG hospital internal control standards were recalculated and compared with the original values. RESULTS: A total of 254 patients were enrolled, including 40 patients with mild malnutrition, 74 patients with moderate malnutrition and 122 patients with severe malnutrition. Of all subjects, 111 changed complication groups. The median of the DRG hospital internal control standard (12006.09 vs. 13797.19, p=0.01) and the median of CMI (0.91 vs. 1.04, p=0.026) were significantly higher than those before the diagnostic change. In patients with inflammatory bowel disease (IBD), the CMI value, hospital control standard of DRG, and the classification of DRG were significantly different from those before diagnosis revision (p<0.001). CONCLUSIONS: Fully identification and correct coding of malnutrition cases are conducive for hospitals to receive appropriate DRG compensation, and further contribute to the improvement of medical quality and the economic sustain-ability of hospitals.

Generation and characterization of iPS cell line (SYSUSHi002-A) from PBMCs of an AML patient with TP53 mutation.

We have generated an iPSCs line (IPS-AML2-C3, SYSUSHi002-A) from AML cells of a 71-year-old male Acute Myeloid Leukaemia patient with TP53 gene mutation (TP53: c.824G > A, p.Cys275Tyr) using episomal plasmids encoding the factors OCT4, SOX2, KLF4, L-MYC and human miR-302. The IPS-AML2-C3 (SYSUSHi002-A) iPSC line displayed typical embryonic stem cell-like morphology, carried the TP53 gene mutation, expressed several pluripotent stem cell makers, retained normal karyotype (46, XY), and was capable of forming three germ layer cells in vitro.

Modulated Arabinose Uptake and cAMP Signaling Synergistically Improve Glucose and Arabinose Consumption in Recombinant Yeast.

During the production of ethanol from lignocellulose-derived sugars, recombinant yeasts tend to utilize xylose and arabinose after glucose exhaustion. So far, many glucose-insensitive pentose transporters have been reported to counteract this phenomenon, but few studies have described intracellular factors. In this study, the combination of adaptive evolution, comparative genomics, and genetic complementation revealed that the hexokinase-deficient (Hxk0) arabinose-fermenting Saccharomyces cerevisiae requires the arabinose transporter variant Gal2-N376T and the mutations of guanine nucleotide exchange factor Cdc25 to overcome glucose restriction during arabinose assimilation. The results showed that the Hxk0 recombinant yeasts could lower the metabolic/physiological threshold of cell proliferation by downregulating the intracellular cAMP levels, resulting in smaller cells and increased arabinose assimilation under glucose restriction. In the medium containing 80 g/L glucose and 20 g/L arabinose, the evolved strain restoring the hexokinase activity completed fermentation at 22 h, compared to 24 h for the parental strain. Overall, the experimental results provide new insights into glucose repression of biorefinery yeasts.

Multi-Responsive Molecular Encapsulation and Release Based on Hydrogen-Bonded Azo-Macrocycle.

Research on stimuli-responsive host-guest systems is at the cutting edge of supramolecular chemistry, owing to their numerous potential applications such as catalysis, molecular machines, and drug delivery. Herein, we present a multi-responsive host-guest system comprising azo-macrocycle 1 and 4,4'-bipyridinium salt G1 for pH-, photo-, and cation- responsiveness. Previously, we reported a novel hydrogen-bonded azo-macrocycle 1. The size of this host can be controlled through light-induced E↔Z photo-isomerization of the constituent azo-benzenes. The host is found in this work to be capable of forming stable complexes with bipyridinium/pyridinium salts, and implementing guest capture and release with G1 under light in a controlled manner. The binding and release of the guest in the complexes can also be easily controlled reversibly by using acid and base. Moreover, the cation competition-induced dissociation of the complex 1a2⊃G1 is achieved. These findings are expected to be useful in regulating encapsulation for sophisticated supramolecular systems.

[Effect and mechanism of amphiregulin on acute respiratory distress syndrome in mice].

OBJECTIVE: To explore the protective effect of amphiregulin (Areg) on acute respiratory distress syndrome (ARDS) in mice and its underlying mechanism. METHODS: (1) Male C57BL/6 mice aged 6-8 weeks were selected for animal experiments and divided into 3 groups (n = 10) according to the random number table method, which includes sham-operated group (Sham group), ARDS model group [ARDS model in mice was established by intratracheal instillation of lipopolysaccharide (LPS) 3 mg/kg] and ARDS+Areg intervention group [recombinant mice Areg (rmAreg) 5 µg was injected intraperitoneally 1 hour after LPS modeling]. The mice were sacrificed at 24 h after LPS injection lung histopathological changes were observed under hematoxylin-eosin (HE) staining and scored for lung injury; oxygenation index and wet/dry ratio of lung tissue were measured; the content of protein in bronchoalveolar lavage fluid (BALF) was detected by bicinchoninic acid (BCA) method, the level of inflammatory factors interleukins (IL-1ß, IL-6) and tumor necrosis factor-α (TNF-α) in BALF were measured by enzyme-linked immunosorbent assay (ELISA). (2) Mice alveolar epithelial cell line MLE12 cells were obtained and cultured for experiment in vitro. Blank control group (Control group), LPS group (LPS 1 mg/L) and LPS+Areg group (rmAreg 50 µg/L was added 1 hour after LPS stimulation) were set. The cells and culture fluid were collected at 24 hours after LPS stimulation, and the apoptosis level of MLE12 cells was detected by flow cytometry; the activation level of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and the expressions of apoptosis-related proteins Bcl-2 and Bax in MLE12 cells were detected by Western blotting. RESULTS: (1) Animal experiments: compared with the Sham group, the lung tissue structure of ARDS model group was destroyed, the lung injury score was significantly increased, the oxygenation index was significantly decreased, the wet/dry weight ratio of lung was significantly increased, and the levels of protein and inflammatory factors in BALF were significantly increased. Compared with ARDS model group, lung tissue structure damage was reduced, pulmonary interstitial congestion, edema and inflammatory cell infiltration were significantly reduced, and lung injury score was significantly decreased (scores: 0.467±0.031 vs. 0.690±0.034) in ARDS+Areg intervention group. In addition, oxygenation index in ARDS+Areg intervention group was significantly increased [mmHg (1 mmHg ≈ 0.133 kPa): 380.00±22.36 vs. 154.00±20.74]. Lung wet/dry weight ratio (5.40±0.26 vs. 6.63±0.25), protein and inflammatory factors levels in BALF [protein (g/L): 0.42±0.04 vs. 0.86±0.05, IL-1ß (ng/L): 30.00±2.00 vs. 40.00±3.65, IL-6 (ng/L): 190.00±20.30 vs. 581.30±45.76, TNF-α (ng/L): 30.00±3.65 vs. 77.00±4.16], and the differences were statistically significant (all P < 0.01). (2) Cell experiments: compared with the Control group, the number of apoptotic MLE12 cells was significantly increased in the LPS group, and the levels of PI3K phosphorylation, anti-apoptotic gene Bcl-2 level and pro-apoptotic gene Bax level were increased in MLE12 cells. Compared with the LPS group, the number of apoptosis in MLE12 cells was significantly reduced in the LPS+Areg group after administration of rmAreg treatment [(17.51±2.12)% vs. (36.35±2.84)%], and the levels of PI3K/AKT phosphorylation and Bcl-2 expression in MLE12 cells were significantly increased (p-PI3K/PI3K: 2.400±0.200 vs. 0.550±0.066, p-AKT/AKT: 1.647±0.103 vs. 0.573±0.101, Bcl-2/GAPDH: 0.773±0.061 vs. 0.343±0.071), and Bax expression was significantly suppressed (Bax/GAPDH: 0.810±0.095 vs. 2.400±0.200). The differences were statistically significant (all P < 0.01). CONCLUSIONS: Areg could alleviate ARDS in mice by inhibiting the apoptosis of alveolar epithelial cells through activating PI3K/AKT pathway.

Complexation and Separation of Palladium with Tridentate 2,6-Bis-triazolyl-pyridine Ligands: Synthesis, Solvent Extraction, Spectroscopy, Crystallography, and DFT Calculations.

Selective extraction of palladium from high-level liquid waste (HLLW) is desirable for the sustainable development of nuclear energy and resource recovery. In this work, three tridentate 2,6-bis-triazolyl-pyridine ligands (L-I, L-II, and L-III) bearing different alkyl side chains were synthesized and systematically studied for the complexation and extraction of palladium. Altering the alkyl side chains of the ligands led to pronounced differences in extraction performance. Among the three ligands, L-II decorated with two n-octyl groups exhibited the highest Pd(II) extraction efficiency at acidity levels of 1-5 M HNO3 and outstanding selectivity over 13 coexisting competing metal ions. Results from UV-vis titration experiments and theoretical calculations suggested that the differentiated extraction abilities of the ligands could be because of their different hydrophilicity rather than electron-donating effects. Slope analyses and electrospray ionization-high resolution mass spectrometry (ESI-HRMS) experiments revealed the formation of both L/Pd 1:1 and 2:1 species during the extraction process. These stoichiometries were further confirmed by job plots and NMR titration experiments. The ligands were found to aggregate slightly, especially at higher concentrations, which could result from multiple intermolecular hydrogen bonds as illustrated by X-ray crystallography. The configurations of PdL and PdL2 were further elucidated by analysis of single crystal structure and density-functional theory (DFT) calculations, respectively, where the first coordination sphere of Pd(II) was surrounded by four nitrogen or oxygen atoms in a quadrangular manner. This study provides an alternative method to separate palladium from HLLW and brings a new understanding of the coordination and complexation behaviors of Pd(II) with tridentate nitrogen ligands.

Impact of sexual intercourse on frozen-thawed embryo transfer outcomes: a randomized controlled trial.

BACKGROUND: Exposure of the female reproductive tract to either seminal plasma or fluid component of the ejaculate is beneficial to achieving successful embryo implantation and normal embryo development. But whether the "physical" component of sexual intercourse during the peri-transfer period have any influence on frozen-thawed embryo transfer (FET) pregnancy outcomes is not clear. METHODS: We conducted a randomized trial that included 223 patients undergoing in vitro fertilization (IVF) treatment at a university-affiliated reproductive center from 19 July 2018 to 24 February 2019. Enrolled patients undergoing IVF treatment were randomized either to engage sexual intercourse using the barrier contraception (Group A, n = 116) or to abstain (Group B, n = 107) one night before FET. The primary outcome was clinical pregnancy rate. RESULTS: Patients having intercourse had higher clinical pregnancy rate (51.72% vs. 37.07%, P = 0.045) and implantation rate (38.31% vs. 24.77%, P = 0.005) compared to those did not engage intercourse. However, there was no significant difference of the spontaneous abortion rate between two groups (11.67% 33 vs. 14.63%, P = 0.662). CONCLUSIONS: Sexual intercourse before embryo transfer may improve the clinical pregnancy and implantation rates during FET cycles. However, it should be noted that patients choose only one time for sexual intercourse, that is, the night before embryo transfer. TRIAL REGISTRATION: The present study was registered at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ , ChiCTR1800017209).

Pexidartinib synergize PD-1 antibody through inhibiting treg infiltration by reducing TAM-derived CCL22 in lung adenocarcinoma.

There is a crosstalk between Tumor-associated macrophages (TAM) and tumor-infiltrating T cells in tumor environment. TAM could inhibit the activity of cytotoxic T cells; TAM could also regulate the composition of T cells in tumor immune environment. The combination therapy for TAM and tumor infiltrated T cells has been widely noticed, but the crosstalk between TAM and tumor infiltrated T cells remains unclear in the process of combination therapy. We treated lung adenocarcinoma tumor models with pexidartinib, which targets macrophage colony stimulating factor receptor (M-CSFR) and c-kit tyrosine kinase, to inhibited TAM. Pexidartinib inhibited the ratio of macrophages in the tumor and also altered macrophage polarization. In addition to reprogram TAM, pexidartinib also changed the composition of tumor-invasive T cells. After pexidartinib treatment, the total number of T cells, CD8+ T cells and Treg cells were all decreased, the ratio of CD8+T/Treg increased significantly. According to the analysis of cytokines and chemokines during the treatment of pexidartinib, CCL22, as a chemokine for Treg recruitment, significantly decreased after the treatment of pexidartinib. Base on the above observation, the combination of pexidartinib and PD-1 antibody were used in the treatment of lung adenocarcinoma subcutaneous tumor model, the combination therapy has significantly improved the efficacy of tumor treatment compared with the monotherapy. Meanwhile, compared with pexidartinib monotherapy, the combination treatment further switches the polarization status of tumor-associated macrophages. In summary, our results showed that the combination of pexidartinib and PD-1 antibody showed a synergy and significantly improved the anti-tumor efficacy, through pexidartinib increasing CD8T/Treg ratio by reducing TAM-derived CCL22.

Selective Complexation and Separation of Uranium(VI) from Thorium(IV) with New Tetradentate N,O-Hybrid Diamide Ligands: Synthesis, Extraction, Spectroscopy, and Crystallographic Studies.

An unmet challenge in the thorium-uranium fuel cycle is the efficient separation of uranium from thorium. Herein, two new tetradentate N,O-hybrid ligands, N,N'-diethyl-N,N'-di-p-tolyl-2,2'-bipyridine-6,6'-dicarboxamide (Et-Tol-BPDA) and N,N'-diethyl-N,N'-di-p-tolyl-2,2'-bipyrimidine-4,4'-dicarboxamide (Et-Tol-BPymDA), comprising a bipyridine or bipyrimidine core and amide moieties were designed and synthesized for selectively complexing and separating U(VI) from Th(IV). The high U(VI)/Th(IV) extraction selectivity was achieved by Et-Tol-BPDA (SFU/Th = 33 at 3 M HNO3) and Et-Tol-BPymDA (SFU/Th = 73 at 3 M HNO3) in nitric acid solutions. The extraction process for U(VI) or Th(IV) with these two ligands primarily proceeded through the solvation mechanism, as evidenced by slope analyses. Thermodynamic studies for the extraction of U(VI) and Th(IV) revealed a spontaneous process. Results from UV-vis spectroscopic titration and slope analyses demonstrated that U(VI) and Th(IV) each form a 1:1 complex with the two ligands both in the monophasic organic solution and the biphasic extraction system. The stability constants of the 1:1 complexes of Et-Tol-BPDA or Et-Tol-BPymDA with U(VI) were found to be larger than those with Th(IV), which coincide well with the high U(VI)/Th(IV) extraction selectivity. The solid-state structures of Et-Tol-BPDA, Et-Tol-BPymDA, and 1:1 complexes of the two ligands with U(VI) or Th(IV) were analyzed by X-ray diffraction technique. The results from this work implicate the potential of bipyridine- and bipyrimidine-derived diamide ligands for uranium/thorium separation.

The Role of Cytoskeleton Protein 4.1 in Immunotherapy.

Cytoskeleton protein 4.1 is an essential class of skeletal membrane protein, initially found in red blood cells, and can be classified into four types: 4.1R (red blood cell type), 4.1N (neuronal type), 4.1G (general type), and 4.1B (brain type). As research progressed, it was discovered that cytoskeleton protein 4.1 plays a vital role in cancer as a tumor suppressor. Many studies have also demonstrated that cytoskeleton protein 4.1 acts as a diagnostic and prognostic biomarker for tumors. Moreover, with the rise of immunotherapy, the tumor microenvironment as a treatment target in cancer has attracted great interest. Increasing evidence has shown the immunoregulatory potential of cytoskeleton protein 4.1 in the tumor microenvironment and treatment. In this review, we discuss the role of cytoskeleton protein 4.1 within the tumor microenvironment in immunoregulation and cancer development, with the intention of providing a new approach and new ideas for future cancer diagnosis and treatment.

Supramolecular Shish Kebabs: Higher Order Dimeric Structures from Ring-in-Rings Complexes with Conformational Adaptivity.

Use of abiotic chemical systems for understanding higher order superstructures is challenging. Here we report a ring-in-ring(s) system comprising a hydrogen-bonded macrocycle and cyclobis(paraquat-o-phenylene) tetracation (o-Box) or cyclobis(paraquat-p-phenylene) tetracation (CBPQT4+ , p-Box) that assembles to construct discrete higher order structures with adaptive conformation. As indicated by mass spectrometry, computational modeling, NMR spectroscopy, and single-crystal X-ray diffraction analysis, this ring-in-ring(s) system features the box-directed aggregation of multiple macrocycles, leading to generation of several stable species such as H4G (1 a/o-Box) and H5G (1 a/o-Box). Remarkably, a dimeric shish-kebab-like ring-in-rings superstructure H7G2 (1 a/o-Box) or H8G2 (1 a/p-Box) is formed from the coaxial stacking of two ring-in-rings units. The formation of such unique dimeric superstructures is attributed to the large π-surface of this 2D planar macrocycle and the conformational variation of both host and guest.

Real-Time Cell Temperature Fluctuation Monitoring System Using Precision Pt Sensors Coated with Low Thermal Capacity, Low Thermal Resistance, and Self-Assembled Multilayer Films.

Real-time monitoring of cell temperature fluctuation can help researchers better understand physiological phenomena and the effects of drug treatment on cells, which is a novel and important tool for cellular informatics. The platinum (Pt) temperature sensor is widely used in temperature measurement with the advantages of strong stability, great accuracy, and high sensitivity. However, the commercially available Pt sensors have large thermal resistance and heat capacity which are difficult to be applied for cell temperature measurement because only a very small amount of heat flux is generated by live cells. In this study, we designed a system using precision Pt thin-film temperature sensors with low heat capacity and thermal resistance. The Pt thin-film sensors are covered by a silicon nitride insulation layer grafted with a self-assembled multilayer silane film for promoting cell adhesion. The temperature coefficient of resistance of the Pt temperature sensor was about 2100 ppm/°C. The four-wire lead design next to the sensor detection area ensured maximum accuracy, resulting in a system noise below 0.01 °C over a long time. HEK-293T and HeLa cells were cultured on the sensor surface, respectively. The temperature fluctuation of 293T cells was monitored in a cell culture medium, showing a temperature increase of about 0.05-0.12 °C. The temperature fluctuation of HeLa cells treated with cisplatin was also measured and recorded, indicating a temperature decrease of 0.01 °C first and then a gradual temperature increase of 0.04 °C. The Pt sensor system we developed demonstrated high sensitivity and long stability for cell temperature fluctuation monitoring, which can be widely used in cell activity and cellular informatics studies.

Chromosome-scale Amaranthus tricolor genome provides insights into the evolution of the genus Amaranthus and the mechanism of betalain biosynthesis.

Amaranthus tricolor is a vegetable and ornamental amaranth, with high lysine, dietary fibre and squalene content. The red cultivar of A. tricolor possesses a high concentration of betalains, which has been used as natural food colorants. Here, we constructed the genome of A. tricolor, the first reference genome for the subgenus Albersia, combining PacBio HiFi, Nanopore ultra-long and Hi-C data. The contig N50 size was 906 kb, and 99.58% of contig sequence was anchored to the 17 chromosomes, totalling 520 Mb. We annotated 27,813 protein-coding genes with an average 1.3 kb coding sequence and 5.3 exons. We inferred that A. tricolor underwent a whole-genome duplication (WGD) and that the WGD shared by amaranths occurred in the last common ancestor of subfamily Amaranthoideae. Moreover, we comprehensively identified candidate genes in betalain biosynthesis pathway. Among them, DODAα1 and CYP76ADα1, located in one topologically associated domain (TAD) of an active (A) compartment on chromosome 16, were more highly expressed in red leaves than in green leaves, and DODAα1 might be the rate-limiting enzyme gene in betalains biosynthesis. This study presents new genome resources and enriches our understanding of amaranth evolution, betalains production, facilitating molecular breeding improvements and the understanding of C4 plants evolution.