14-3-3 binding motif phosphorylation disrupts Hdac4-organized condensates to stimulate cardiac reprogramming.

Cell fate conversion is associated with extensive post-translational modifications (PTMs) and architectural changes of sub-organelles, yet how these events are interconnected remains unknown. We report here the identification of a phosphorylation code in 14-3-3 binding motifs (PC14-3-3) that greatly stimulates induced cardiomyocyte (iCM) formation from fibroblasts. PC14-3-3 is identified in pivotal functional proteins for iCM reprogramming, including transcription factors and chromatin modifiers. Akt1 kinase and protein phosphatase 2A are the key writer and key eraser of the PC14-3-3 code, respectively. PC14-3-3 activation induces iCM formation with the presence of only Tbx5. In contrast, PC14-3-3 inhibition by mutagenesis or inhibitor-mediated code removal abolishes reprogramming. We discover that key PC14-3-3-embedded factors, such as histone deacetylase 4 (Hdac4), Mef2c, and Foxo1, form Hdac4-organized inhibitory nuclear condensates. PC14-3-3 activation disrupts Hdac4 condensates to promote cardiac gene expression. Our study suggests that sub-organelle dynamics regulated by a PTM code could be a general mechanism for stimulating cell reprogramming.

Enhancing Iodine Capture of Porous Organic Cages through N-Heteroatom Engineering.

Iodine radioisotopes, produced or released during nuclear-related activities, severely affect human health and the environment. The efficient removal of radioiodine from both aqueous and vapor phases is crucial for the sustainable development of nuclear energy. In this study, we propose an "N-heteroatom engineering" strategy to design three porous organic cages with N-containing functional groups for efficient iodine capture. Among the molecular cages investigated, FT-Cage incorporating tertiary amine groups and RT-Cage with secondary amine groups show higher adsorption capacity and much faster iodine release compared to IT-Cage with imine groups. Detailed investigations demonstrate the superiority of amine groups, along with the influence of crystal structures and porosity, for iodine capture. These findings provide valuable insights for the design of porous organic cages with enhanced capabilities for capturing iodine.

14-3-3 binding motif phosphorylation disrupts Hdac4 organized condensates to stimulate cardiac reprogramming.

Cell fate conversion is associated with extensive epigenetic and post translational modifications (PTMs) and architectural changes of sub-organelles and organelles, yet how these events are interconnected remains unknown. We report here the identification of a phosphorylation code in 14-3-3 binding motifs (PC14-3-3) that greatly stimulates induced cardiomyocyte (iCM) formation from fibroblasts. PC14-3-3 was identified in pivotal functional proteins for iCM reprogramming, including transcription factors and epigenetic factors. Akt1 kinase and PP2A phosphatase were a key writer and eraser of the PC14-3-3 code, respectively. PC14-3-3 activation induces iCM formation with the presence of only Tbx5. In contrast, PC14-3-3 inhibition by mutagenesis or inhibitor-mediated code removal abolished reprogramming. We discovered that key PC14-3-3 embedded factors, such as Hdac4, Mef2c, Nrip1, and Foxo1, formed Hdac4 organized inhibitory nuclear condensates. Notably, PC14-3-3 activation disrupted Hdac4 condensates to promote cardiac gene expression. Our study suggests that sub-organelle dynamics regulated by a post-translational modification code could be a general mechanism for stimulating cell reprogramming and organ regeneration. Highlights: A PC14-3-3 (phosphorylation code in 14-3-3 binding motifs) is identified in pivotal functional proteins, such as HDAC4 and Mef2c, that stimulates iCM formation.Akt1 kinase and PP2A phosphatase are a key writer and a key eraser of the PC14-3-3 code, respectively, and PC14-3-3 code activation can replace Mef2c and Gata4 in cardiac reprogramming.PC14-3-3 activation disrupts Hdac4 organized condensates which results in releasing multiple 14-3-3 motif embedded proteins from the condensates to stimulate cardiac reprogramming.Sub-organelle dynamics and function regulated by a post-translational modification code could be a general mechanism in stimulating cell reprogramming and organ regeneration.

Nuclear Acly protects the liver from ischemia-reperfusion injury.

BACKGROUND AND AIMS: Hepatic ischemia-reperfusion (IR) injury is the most common complication that occurs in liver surgery and hemorrhagic shock. ATP citrate lyase (Acly) plays a pivotal role in chromatin modification via generating acetyl-CoA for histone acetylation to influence biological processes. We aim to examine the roles of Acly, which is highly expressed in hepatocytes, in liver IR injury. APPROACH AND RESULTS: The functions of Acly in hepatic IR injury were examined in the mouse model with a hepatocyte-specific knockout of Acly . The Acly target genes were analyzed by CUT&RUN assay and RNA sequencing. The relationship between the susceptibility of the steatotic liver to IR and Acly was determined by the gain of function studies in mice. Hepatic deficiency of Acly exacerbated liver IR injury. IR induced Acly nuclear translocation in hepatocytes, which spatially fueled nuclear acetyl-CoA. This alteration was associated with enhanced acetylation of H3K9 and subsequent activation of the Foxa2 signaling pathway. Nuclear localization of Acly enabled Foxa2-mediated protective effects after hypoxia-reperfusion in cultured hepatocytes, while cytosolic Acly demonstrated no effect. The presence of steatosis disrupted Acly nuclear translocation. In the steatotic liver, restoration of Acly nuclear localization through overexpression of Rspondin-1 or Rspondin-3 ameliorated the IR-induced injury. CONCLUSIONS: Our results indicate that Acly regulates histone modification by means of nuclear AcCoA production in hepatic IR. Disruption of Acly nuclear translocation increases the vulnerability of the steatotic liver to IR. Nuclear Acly thus may serve as a potential therapeutic target for future interventions in hepatic IR injury, particularly in the context of steatosis.

Two new furanone derivatives from the endophytic fungus Byssochlamys sp. and their cytotoxic activities.

Two new furanone derivatives, byssochlanones A-B (1-2) were purified from the endophytic fungus Byssochlamys sp. isolated from the wetland plant, Phragmites australis. Their structures were elucidated on the basis of extensive spectroscopic analyses. Compounds 1-2 represented typical furanone analogues which are not common in natural products. The absolute configuration of compounds 1-2 were identified through quantum-chemical electronic circular dichroism (ECD) calculation compared with their experimental CD. In addition, compounds 1-2 were tested for their cytotoxic activities against HCT-8 and Hela cancer cell lines, and compound 2 showed moderate activity against HCT-8 cells with IC50 value of 21.3 µM.

The Functions and Mechanisms of Long Non-coding RNA SNHGs in Gastric Cancer.

Gastric cancer is one of the most common malignancies worldwide. Despite significant advancements in surgical and adjuvant treatments, patient prognosis remains unsatisfactory. Long non-coding RNAs (lncRNAs) are a class of RNA molecules that lack protein-coding capacity but can participate in various mechanisms of tumor malignancy. Among them, small nucleolar host genes (SNHGs) represent a subgroup of lncRNAs. Studies have revealed their involvement not only in gastric cancer cell proliferation, invasion, migration, epithelialmesenchymal transition (EMT), and apoptosis but also in chemotherapy resistance and tumor stemness. This review comprehensively summarizes the biological functions, molecular mechanisms, and clinical significance of SNHGs in gastric cancer. It provides novel insights into potential biomarkers and therapeutic targets for the exploration of gastric cancer.

Oxygen-limited pyrolysis and incineration impact on biochar transport.

At present, studies on biochar transport have focused on biochar obtained by oxygen-limited pyrolysis, which may differ from conventional biochar produced by incineration in nature. This work investigated the transport and retention mechanisms of three types of oxygen-limited pyrolytic biochar and three types of traditional biochar in saturated porous media. The results showed that the specific surface area of the three oxygen-limited pyrolysis biochar (180-200 m2·g-1) was higher than that of the traditional biochar (50-60 m2·g-1). Therefore, the retention capacity of pyrolytic biochar is strong and the permeability is less than 0.1. The absolute value of the zeta potential of traditional biochar is greater than 30 mV, and the electrostatic repulsion generated is stronger, with a peak penetration rate of 0.16. Moreover, the zeta potential of biochar and traditional biochar is regulated by pH value and ionic strength. In acidic conditions or solutions with high ionic strength, the zeta potentials of the six types of biochar changed to about - 15 mV, and the second minimum value was less than 0, indicating that there was a tendency for sedimentation. This study provides a new perspective for assessing the transport and environmental risks of biochar in the environment.

Chiral Molecular Cage with Tunable Stereoinversion Barriers.

The manipulation of chirality in molecular entities that rapidly interconvert between enantiomeric forms is challenging, particularly at the supramolecular level. Advances in controlling such dynamic stereochemical systems offer opportunities to understand chiral symmetry breaking and homochirality. Herein, we report the synthesis of a face-rotating tetrahedron (FRT), an organic molecular cage composed of tridurylborane facial units that undergo stereomutations between enantiomeric trefoil propeller-like conformations. After resolution, we show that the racemization barrier of the enantiopure FRT can be regulated in situ through the reversible binding of fluoride anions onto the tridurylborane moieties. Furthermore, the addition of an enantiopure phenylethanol to the FRT can effectively induce chirality of the molecular cage by preferentially binding to one of its enantiomeric conformers. This study presents a new paradigm for controlling dynamic chirality in supramolecular systems, which may have implications for asymmetric synthesis and dynamic stereochemistry.

Inhibition of AGEs-RAGE-PP2A Axis Alleviates Cognitive Impairment after Chronic Heart Failure.

To investigate the effect of the AGEs-RAGE-PP2A axis on cognitive impairment (CI) after chronic heart failure (CHF). Mice were divided into six groups: Sham, TAC, Sham+RAGE-/-, TAC+RAGE-/-, AG, and FTY720 group. AG mice and FTY720 mice were treated with AGEs inhibitor (aminoguanidine, AG) and PP2A activator (FTY720) respectively after TAC surgery. The cardiac function of AG and TAC+RAGE-/- mice was significantly better than that of TAC mice (P<0.05). However, the heart function of FTY720 mice were just improved a part of that. To behavioral function, the escape latency period of the TAC+RAGE-/-, AG and FTY720 mice were significantly shorter (P<0.05), and the times of platform crossings and residence time of them were significantly improved (P<0.05). HE staining and silver staining show the structure of TAC+RAGE-/-, AG and FTY720 mice were more complete. Also, in these three groups, the expression of Aß and p-tau protein in the brain can be significantly down-regulated (P<0.05) and the PP2A protein expression level was up-regulated (P<0.05). And the expression of hippocampal Bax, Cyt-C, and Caspase-3 of that were all down-regulated (P<0.05), and Bcl-2 was up-regulated (P<0.05). Deficient of AGEs, RAGE and activating PP2A can significantly attenuate the cognitive impairment in CHF mice, and protect the brain structure. This mechanism seems via reducing the expression of Aß, p-tau, and apoptotic protein.

Genome mosaic structure of two novel HIV-1 recombinant forms (CRF01_AE/B) in men who have sex with men in Hebei, China.

BACKGROUND: Homosexual contact is the main route of human immunodeficiency virus type one (HIV-1) transmission in Cangzhou Prefecture, Hebei, China. Moreover, the number of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) in this key population is ever increasing. METHODS: In this study, we identified two novel URFs (hcz0017 and hcz0045) from two men who have sex with men (MSM) based in Cangzhou Prefecture. Phylogenetic and recombinant breakpoint analyses, based on the near full-length genomes (NFLGs) of the two novel URFs, showed that they originated from a recombination between HIV-1 CRF01_AE and subtype B. RESULTS: HXB2 numbering revealed that the NFLGs of hcz0017 and hcz0045 each contained the following seven subregions: hcz0017: IB (790-1,171 nt), IICRF01_AE (1,172-2,022 nt), IIIB (2,023-4,469 nt), IVCRF01_AE (4,470-5,866 nt), VB (5,867-7,462 nt), VICRF01_AE (7,463-8,379 nt), VIIB (8,380-9,411 nt); hcz0045: ICRF01_AE (790-5,147 nt), IIB (5,148-5,614 nt), IIICRF01_AE (5,615-6,035 nt), IVB (6,036-6,241 nt), VCRF01_AE (6,242-7,325nt), VIB (7,326-8,254 nt), VIICRF01_AE (8,255-9,411 nt). Moreover, the two MSM from whom the novel URFs originated from were diagnosed as recently HIV-1-infected, suggesting that the high prevalence of HIV-1 among MSM was related to high-risk sexual activity such as unprotected anal sex and multiple sexual partners. CONCLUSIONS: Our results highlight the need to continually monitor HIV-1 diversity in Hebei and its neighboring provinces to achieve a more effective control of HIV-1 spread within the MSM community.

Carcinoma with signet ring cell differentiation associated with invasive breast cancer: A case report.

Carcinoma with signet ring cell differentiation is uncommon in patients with invasive breast cancer. Clinical evidence has suggested that the prognosis of this tumor is usually poor if the stage is advanced. The case of a 40-year-old female patient with primary cancer in the right breast accompanied by bilateral neck, axillary, right subclavian and mediastinal lymph node metastases, and left breast metastasis is presented in the current study. The patient developed superior vena cava syndrome and was restricted in lifting the upper right limb when presenting at the Third Affiliated Hospital of Shenzhen University, Shenzhen. The histopathological and immunohistochemical features included ~80% of the tumor cell area having a signet ring cell pattern, exhibiting the phenotype of lobular carcinoma, and ~20% of the tumor cell area exhibiting a ductal carcinoma immunophenotype with neuroendocrine expression The patient received chemotherapy with paclitaxel liposomes and doxorubicin hydrochloride liposomes according to the general guidelines for the treatment of stage IV breast carcinoma. The patient achieved a partial response after 4 cycles of treatment, and then experienced progressive disease in the form of brain metastasis after 6 cycles. Owing to the rarity of carcinoma with signet ring cell differentiation in invasive breast carcinoma, this case report discusses the patient's clinical and histopathological characteristics, and the treatment prognosis.

Biclonal lymphoplasmacytic lymphoma/Waldenström macroglobulinemia associated with POEMS syndrome: A case report and literature review.

Due to its unique clinical, immunological and molecular genetic characteristics, biclonal lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes (POEMS) syndrome is extremely rare in clinical practice, and there is no standard treatment for patients afflicted with this condition. In the present case report, a rare case of double LPL/WM with POEMS syndrome is described. The patient, a 65-year-old male, exhibited significant renal impairment and polylymphadenopathy. The patient was treated with rituximab and his symptoms were resolved following two courses of treatment. A review of the literature was performed, comparing the present case with previous cases. It is hoped that this case report will enable clinicians to gain a better understanding of this disease.

A prognostic nomogram for predicting overall survival in colorectal mucinous adenocarcinoma patients based on the SEER database.

A nomogram was constructed to predict the survival of patients with colorectal mucinous adenocarcinoma based on data extracted from the Surveillance, Epidemiology and End Result (SEER) database. Data collected between 2010 and 2018 were obtained from the SEER database. The log-rank test and multivariate Cox regression were performed to identify the independent prognostic factors for overall survival, which were further used to construct a nomogram model to predict 1-, 3-, and 5-year overall survival. In total, 10846 patients diagnosed with colorectal mucinous adenocarcinoma were enrolled in the study. The following 11 variables were associated with survival and were further incorporated into the nomogram: age at diagnosis, primary site, grade, tumour size, lymph node dissection, T stage, N stage, M stage, surgery for primary site, chemotherapy, and household income. The concordance index (C-index) value was 0.725 (95% confidence interval 0.716-0.734), and the receiver operating characteristic curves and calibration curves showed satisfactory predictive accuracy. Both the C-index and time-independent area under the curve values were greater than those of the American Joint Committee on Cancer 7th TNM classification system (both P < 0.001). In the validation group, the results were consistent with those of the training group, with a C-index value of 0.726 (95% confidence interval 0.713-0.739). This study constructed a practical nomogram to predict 1-, 3-, and 5-year OS for patients with colorectal colorectal mucinous adenocarcinoma based on SEER data.

Anti-inflammatory Polyketides from the Marine-Derived Fungus Eutypella scoparia.

Three new polyketides, eutyketides A and B (1 and 2) and cytosporin X (3), along with four known compounds (4-7), were obtained from the marine-derived fungus Eutypella scoparia. The planar structures of 1 and 2 were elucidated by extensive HRMS and 1D and 2D NMR analyses. Their relative configurations of C-13 and C-14 were determined with chemical conversions by introducing an acetonylidene group. The absolute configurations of 1-3 were determined by comparing their experimental electronic circular dichroism (ECD) data with their computed ECD results. All of the isolated compounds were tested for their anti-inflammatory activities on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages. Compounds 5 and 6 showed stronger anti-inflammatory activities than the other compounds, with the inhibition of 49.0% and 54.9% at a concentration of 50.0 µg/mL, respectively.

BCOFGs loaded with nano-FexSy for the catalytic degradation of QNC: Contribution and mechanism of OFGs for reductive iron regeneration.

Biochar currently served as the support for dispersed metal nanoparticles and cooperated with pyrite to generate more reactive radicals in organic pollution degradation system. But the mechanism of interaction between biochar and pyrite has not been elucidated. In this paper, biochar with oxygen-containing functional groups (OFGs) served as a stable dispersant to prepare nano-FexSy loaded biochar materials (BCOFGs@nano-FexSy). BCOFGs coordinated with nano-FexSy to overcome its drawbacks, boosting QNC removal efficiency from 28.64% to 100%. The XPS and the linear sweep voltammetry (LSV) results revealed higher Fe(II) content and higher electron transfer rate on used BCOFGs@nano-FexSy, further validating that hydroxyl functional groups on biochar surface provided electrons to Fe(III) to achieve efficient Fe(II)/Fe(III) cycling. Based on comparative experiments and studies on the roles of iron, S(II) species and OFGs, we clearly revealed that OFGs on biochar materials surface coordinated with nano-FexSy to catalyze the degradation of QNC. The degradation efficiency of BCOFGs@nano-FexSy for QNC was still as high as 91.39% after five cycles, providing full demonstrations that OFGs and S(II) as the abundant electron donor coordinated with Fe species for QNC catalytic degradation and further enhanced the catalytic performance and stability of nano-FexSy.

Efficacy and safety of triplet chemotherapy plus anti-EGFR agents in metastatic colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: To date, the optimal treatment for potentially resectable metastatic colorectal cancer (mCRC) patients has yet to be determined. Encouraging results have been reported in studies exploring the efficacy of triplet chemotherapy plus anti-epidermal growth factor receptor (anti-EGFR) target agents. Thus, we conducted a meta-analysis to evaluate the efficacy and safety of triplet chemotherapy plus anti-EGFR target agents. METHODS: We systematically searched the PubMed, Embase, and Web of Science databases from December 2004 to October 2021 for studies examining the efficacy of triplet chemotherapy plus anti-EGFR target agents in mCRC patients. The primary outcomes were the objective response rate (ORR) and R0 resection rate (R0RR), and the secondary outcomes were median progression-free survival (mPFS), median overall survival (mOS), and toxicity. Data were analyzed with R software 4.1.2. RESULTS: Fourteen studies comprising 762 patients with mCRC were included in this meta-analysis. Analysis with a random effects model revealed that after treatment with triplet chemotherapy plus anti-EGFR target agents, the pooled ORR was 82% (95% CI= 76-88%, I2= 76%), and the pooled R0RR of colorectal liver metastasis (CLM) was 59% (95% CI= 49-68%, I2= 60%). The mPFS ranged from 9.5 to 17.8 months, and the mOS ranged from 24.7 to 62.5 months. A total of 648 grade 3 or 4 adverse events were reported; the most commonly reported events were diarrhea (174/648), neutropenia (157/648), and skin toxicity (95/648), which had pooled prevalence rates of 29% (95% CI= 20-39%, I2= 84%), 28% (95% CI= 20-37%, I2= 77%), and 17% (95% CI= 11-24%, I2= 66%), respectively. CONCLUSIONS: Triplet chemotherapy plus anti-EGFR agents therapy seems to be capable of increasing the ORR of mCRC patients and the R0RR of CLM patients. The toxicity of this treatment is manageable. High-quality randomized controlled trial (RCT) studies are required for further validation.

A dual-responsive "Yin-Yang" photothermal delivery system to accelerate Parthenolide anti-tumor efficacy.

Parthenolide (PTL), a germacrane sesquiterpene lactone extracted from the "Yin" Chinese traditional herb feverfew, has gained interest due to its lethal effects on tumor cells and its pharmacological effects within traditional Chinese medicine theory. To overcome low, non-targeted accumulation and uncontrolled release of PTL administration, a dual-responsive PTL-liposomes@chitosan@gold nanoshells (PTL-Lips@CS@GNS) system was fabricated. Hyperthermia generated under light irradiation in the near-infrared region via local surface plasmon resonance of gold nanoshells induced photothermal therapy, which also stimulated PTL release due to the liposomes gel-to-liquid crystalline phase transition. Additionally, PTL-Lips@CS@GNS exhibited a pH-responsive release in the acidic tumor microenvironment. Collectively, this study provides a realistic strategy for an effective combination of traditional Chinese medicine and current nanotechnology for tumor therapy.

Promoting Effect of Horticultural Therapy on College Students' Positive Psychological Quality.

To explore the effect of horticultural therapy on cultivating College Students' positive psychological quality and to provide reference for college students' mental health education, 176 college students were randomly divided into experimental group (n = 88) and control group (n = 88). The experimental group was intervened by horticulture therapy, and the Chinese college students' mental health evaluation system and Chinese college students' positive psychological quality scale were used to test the experimental group and the control group. There was no difference in the six dimensions of positive psychological quality between the experimental group and the control group in the pre-test. After 9 weeks of intervention, the differences between the experimental group and the control group in the "cognitive dimension" and "emotional dimension" were significant. The scores of emotional dimension and transcendental dimension in the experimental group were higher than those in the pre-test (all p < 0.05); meanwhile, there is no difference in the other four dimensions. Horticultural therapy can promote the positive psychological quality of college students.