Prominent Intrinsic Proton Conduction in Two Robust Zr/Hf Metal-Organic Frameworks Assembled by Bithiophene Dicarboxylate.

To date, developing crystalline proton-conductive metal-organic frameworks (MOFs) with an inherent excellent proton-conducting ability and structural stability has been a critical priority in addressing the technologies required for sustainable development and energy storage. Bearing this in mind, a multifunctional organic ligand, 3,4-dimethylthiophene[2,3-b]thiophene-2,5-dicarboxylic acid (H2DTD), was employed to generate two exceptionally stable three-dimensional porous Zr/Hf MOFs, [Zr6O4(OH)4(DTD)6]·5DMF·H2O (Zr-DTD) and [Hf6O4(OH)4(DTD)6]·4DMF·H2O (Hf-DTD), using solvothermal means. The presence of Zr6 or Hf6 nodes, strong Zr/Hf-O bonds, the electrical influence of the methyl group, and the steric effect of the thiophene unit all contribute to their structural stability throughout a wide pH range as well as in water. Their proton conductivity was fully examined at various relative humidities (RHs) and temperatures. Creating intricate and rich H-bonded networks between the guest water molecules, coordination solvent molecules, thiophene-S, -COOH, and -OH units within the framework assisted proton transfer. As a result, both MOFs manifest the maximum proton conductivity of 0.67 × 10-2 and 4.85 × 10-3 S·cm-1 under 98% RH/100 °C, making them the top-performing proton-conductive Zr/Hf-MOFs. Finally, by combining structural characteristics and activation energies, potential proton conduction pathways for the two MOFs were identified.

Cyclin-dependent kinase 12 deficiency reprogrammes cellular metabolism to alleviate ferroptosis potential and promote the progression of castration-resistant prostate cancer.

BACKGROUND: Cyclin-dependent kinase 12 (CDK12)-deficient prostate cancer defines a subtype of castration-resistant prostate cancer (CRPC) with a poor prognosis. Current therapy, including PARP inhibitors, shows minimal treatment efficacy for this subtype of CRPC, and the underlying mechanism remains elusive. METHODS: Based on bioinformatics analysis, we evaluated the relationship between CDK12 deficiency and prostate cancer patient's prognosis and treatment resistance. Furthermore, we used CRISPR-Cas9 technology and mass spectrometry-based metabolomic profiling to reveal the metabolic characteristics of CDK12-deficient CRPC. To elucidate the specific mechanisms of CDK12 deficiency-mediated CRPC metabolic reprogramming, we utilized cell RNA-seq profiling and other molecular biology techniques, including cellular reactive oxygen species probes, mitochondrial function assays, ChIP-qPCR and RNA stability analyses, to clarify the role of CDK12 in regulating mitochondrial function and its contribution to ferroptosis. Finally, through in vitro drug sensitivity testing and in vivo experiments in mice, we identified the therapeutic effects of the electron transport chain (ETC) inhibitor IACS-010759 on CDK12-deficient CRPC. RESULTS: CDK12-deficient prostate cancers reprogramme cellular energy metabolism to support their aggressive progression. In particular, CDK12 deficiency enhanced the mitochondrial respiratory chain for electronic transfer and ATP synthesis to create a ferroptosis potential in CRPC cells. However, CDK12 deficiency downregulated ACSL4 expression, which counteracts the lipid oxidation stress, leading to the escape of CRPC cells from ferroptosis. Furthermore, targeting the ETC substantially inhibited the proliferation of CDK12-deficient CRPC cells in vitro and in vivo, suggesting a potential new target for the therapy of CDK12-deficient prostate cancer. CONCLUSIONS: Our findings show that energy and lipid metabolism in CDK12-deficient CRPC work together to drive CRPC progression and provide a metabolic insight into the worse prognosis of CDK12-deficient prostate cancer patients. KEY POINTS: CDK12 deficiency promotes castration-resistant prostate cancer (CRPC) progression by reprogramming cellular metabolism. CDK12 deficiency in CRPC leads to a more active mitochondrial electron transport chain (ETC), ensuring efficient cell energy supply. CDK12 phosphorylates RNA Pol II to ensure the transcription of ACSL4 to regulate ferroptosis. Mitochondrial ETC inhibitors exhibit better selectivity for CDK12-deficient CRPC cells, offering a promising new therapeutic approach for this subtype of CRPC patients.

Superprotonic conductivity of ketoenamine covalent-organic frameworks grafted by imidazole-based units.

The achievement of covalent organic frameworks (COFs) with high stability and exceptional proton conductivity is of tremendous practical importance and challenge. Given this, we hope to prepare the highly stable COFs carrying CN connectors and enhance their proton conductivity via a post-modification approach. Herein, one COF, TpTta, was successfully synthesized by employing 1,3,5-triformylphloroglucinol (Tp) and 4,4',4″-(1,3,5-triazine-2,4,6-triyl)-trianiline (Tta) as starting materials, which has a ß-ketoenamine structure bearing a large amount of -NH groups and intramolecular H-bonds. TpTta was then post-modified by inserting imidazole (Im) and histamine (His) molecules, yielding the corresponding COFs, Im@TpTta and His@TpTta, respectively. As a result, their proton conductivities were surveyed under changeable temperatures (30-100 °C) and relative humidities (68-98 %), revealing a degree of temperature and humidity dependence. Impressively, under identical conditions, the optimum proton conductivities of the two post-modified COFs are 1.14 × 10-2 (Im@TpTta) and 3.45 × 10-3 S/cm (His@TpTta), which are significantly greater than that of the pristine COF, TpTta (2.57 × 10-5 S/cm). Finally, their proton conduction mechanisms were hypothesized based on the computed activation energy values, water vapor adsorption values, and structural properties of these COFs. Additionally, the excellent electrochemical stability of the produced COFs was expressed, as well as the prospective application value.

Overcoming Endosomal Escape Barriers in Gene Drug Delivery Using De Novo Designed pH-Responsive Peptides.

A major challenge in using nanocarriers for intracellular drug delivery is their restricted capacity to escape from endosomes into the cytosol. Here, we significantly enhance the drug delivery efficiency by accurately predicting and regulating the transition pH (pH0) of peptides to modulate their endosomal escape capability. Moreover, by inverting the chirality of the peptide carriers, we could further enhance their ability to deliver nucleic acid drugs as well as antitumor drugs. The resulting peptide carriers exhibit versatility in transfecting various cell types with a high efficiency of up to 90% by using siRNA, pDNA, and mRNA. In vivo antitumor experiments demonstrate a tumor growth inhibition of 83.4% using the peptide. This research offers a potent method for the rapid development of peptide vectors with exceptional transfection efficiencies for diverse pathophysiological indications.

Four Lanthanide(III) Metal-Organic Frameworks Fabricated by Bithiophene Dicarboxylate for High Inherent Proton Conduction.

Currently, it is still a challenge to directly achieve highly stable metal-organic frameworks (MOFs) with superior proton conductivity solely through the exquisite design of ligands and the attentive selection of metal nodes. Inspired by this, we are intrigued by a multifunctional dicarboxylate ligand including dithiophene groups, 3,4-dimethylthieno[2,3-b]thiophene-2,5-dicarboxylic acid (H2DTD), and lanthanide ions with distinct coordination topologies. Successfully, four isostructural three-dimensional lanthanide(III)-based MOFs, [Ln2(DTD)3(DEF)4]·DEF·6H2O [LnIII = TbIII (Tb-MOF), EuIII (Eu-MOF), SmIII (Sm-MOF), and DyIII (Dy-MOF)], were solvothermally prepared, in which the effective proton transport will be provided by the coordinated or free solvent molecules, the crystalline water molecules, and the framework components, as well as a large number of highly electronegative S and O atoms. As expected, the four Ln-MOFs demonstrated the highest proton conductivities (σ) being 0.54 × 10-3, 3.75 × 10-3, 1.28 × 10-3, and 1.92 × 10-3 S·cm-1 for the four MOFs, respectively, at 100 °C/98% relative humidity (RH). Excitingly, Dy-MOF demonstrated an extraordinary ultrahigh σ of 1 × 10-3 S·cm-1 at 30 °C/98% RH. Additionally, the plausible proton transport mechanisms were emphasized.

Predictors of achieving minimal clinically important difference in functional status for elderly patients with degenerative lumbar spinal stenosis undergoing lumbar decompression and fusion surgery.

OBJECTIVE: To identify the predictors for the achievement of minimal clinically important difference (MCID) in functional status among elderly patients with degenerative lumbar spinal stenosis (DLSS) undergoing lumbar decompression and fusion surgery. METHODS: Patients who underwent lumbar surgery for DLSS and had a minimum of 1-year follow-up were included. The MCID achievement threshold for the Oswestry Disability Index (ODI) was set at 12.8. General patient information and the morphology of lumbar paraspinal muscles were evaluated using comparative analysis to identify influencing factors. Multiple regression models were employed to identify predictors associated with MCID achievement. A receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cut-off values for predicting functional recovery. RESULTS: A total of 126 patients (46 males, 80 females; mean age 73.0 ± 5.9 years) were included. The overall rate of MCID achievement was 74.6%. Patients who achieved MCID had significantly higher psoas major muscle attenuation (43.55 vs. 39.23, p < 0.001) and preoperative ODI (51.5 vs. 41.6, p < 0.001). Logistic regression showed that elevated psoas major muscle attenuation (p = 0.001) and high preoperative ODI scores (p = 0.001) were independent MCID predictors. The optimal cut-off values for predicting MCID achievement were found to be 40.46 Hounsfield Units for psoas major muscle attenuation and 48.14% for preoperative ODI. CONCLUSION: Preoperative psoas major muscle attenuation and preoperative ODI were reliable predictors of achieving MCID in geriatric patients undergoing lumbar decompression and fusion surgery. These findings offer valuable insights for predicting surgical outcomes and guiding clinical decision-making in elderly patients.

Psoas muscle index and psoas muscle density are associated with functional status in patients with degenerative lumbar spinal stenosis.

BACKGROUND: The factors affecting lumbar spinal function in patients with degenerative lumbar spinal stenosis (DLSS) are still unclear. OBJECTIVE: This study explored psoas major muscle morphology in patients with DLSS and its association with their functional status. METHODS: A retrospective study was conducted on 288 patients with DLSS and 260 control subjects. Psoas major muscle evaluation included three morphometric parameters at the L3/4 disc level: psoas major index (PMI), muscle attenuation, and psoas major morphological changes (MPM). The association between psoas major morphology and functional status was assessed using the Oswestry disability index (ODI). RESULTS: Both female and male patients with DLSS had a higher PMI and lower muscle attenuation. PMI and muscle attenuation were inversely correlated with age in the DLSS group. After multivariable analyses, the PMI and psoas major muscle attenuation were positively correlated with patients' functional status. CONCLUSION: The PMI and muscle attenuation were positively correlated with functional status in patients with DLSS. These findings have important implications for physiotherapy programs of postoperative rehabilitation and conservative management of DLSS.

Ligand-Functionalized MIL-68-type Indium(III) Metal-Organic Frameworks with Prominent Intrinsic Proton Conductivity.

Indium-based metal-organic frameworks (In-MOFs) have now become an attractive class of porous solids in materials science and electrochemistry due to their diverse structures and promising applications. In the field of proton conduction, to find more crystalline MOFs with splendid proton-conductive properties, herein, five three-dimensional isostructural In-MOFs, MIL-68-In or MIL-68-In-X (X = NH2, OH, Br, or NO2) using terephthalic acid (H2BDC) or functionalized terephthalic acids (H2BDC-X) as multifunctional linkages were efficiently fabricated. First, the outstanding structural stability of the five MOFs, including thermal and water stability, was verified by thermal analysis and powder X-ray diffraction. Subsequently, the H2O-mediated proton conductivities (σ) were fully assessed and compared. Notably, their σ evinced a significant positive correlation between the temperature or relative humidity (RH) and varied with the functional groups on the organic ligands. Impressively, their highest σ values are up to 10-3-10-4 S/cm (100 °C/98% RH) and change in this order: MIL-68-In-OH (1.72 × 10-3 S/cm) > MIL-68-In-NH2 (1.70 × 10-3 S/cm) > MIL-68-In-NO2 (4.47 × 10-4 S/cm) > MIL-68-In-Br (4.11 × 10-4 S/cm) > MIL-68-In (2.37 × 10-4 S/cm). Finally, the computed activation energy values under 98 or 68% RHs are assessed, and the related proton conduction mechanisms are speculated. Moreover, after electrochemical testing, these MOFs illustrate remarkable structural rigidity, laying a meritorious material foundation for future applications.

Protective effect of chitosan-modified rice porous starch loaded catechin on HT-29 cells exposed to lead ion.

To explore how chitosan-modified rice porous starch-loaded catechin (CT@RPS/CS) protects HT-29 cells exposed to lead ions. METHOD: The HT-29 cells were treated differently based on their grouping. The effect of CT@RPS/CS on lead-induced toxicity was evaluated using cell proliferation, apoptosis, oxidative stress index, and cytokine tests. RESULTS: CT@RPS/CS did not affect the activity, cell apoptosis, oxidative stress level, and related cytokines of HT-29 cells. After exposure to lead, CT@RPS/CS has the potential to enhance cellular activity, minimize apoptosis, and decrease the level of oxidative stress. DISCUSSION: CT@RPS/CS not only has no toxicity to cells but also adsorbs lead ions, which protects cells.

YTHDC1 as a tumor progression suppressor through modulating FSP1-dependent ferroptosis suppression in lung cancer.

Ferroptosis is a regulated cell death process initiated by iron-dependent phospholipid peroxidation and is mainly suppressed by GPX4-dependent and FSP1-dependent surveillance mechanisms. However, how the ferroptosis surveillance system is regulated during cancer development remains largely unknown. Here, we report that the YTHDC1-mediated m6A epigenetic regulation of FSP1 alleviates the FSP1-dependent ferroptosis suppression that partially contributes to the tumor suppressive role of YTHDC1 in lung cancer progression. YTHDC1 knockdown promoted the lung tumor progression and upregulated FSP1 protein level that resulted in ferroptosis resistance of lung cancer cells. Silencing FSP1 abrogated YTHDC1 knockdown-induced proliferation increase and ferroptosis resistance. Mechanistically, YTHDC1 binding to the m6A sites in the FSP1 3'-UTR recruited the alternative polyadenylation regulator CSTF3 to generate a less stable shorter 3'-UTR contained FSP1 mRNA, whereas YTHDC1 downregulation generated the longer 3'-UTR contained FSP1 mRNA that is stabilized by RNA binding protein HuR and thus led to the enhanced FSP1 protein level. Therefore, our findings identify YTHDC1 as a tumor progression suppressor in lung cancer and a ferroptosis regulator through modulating the FSP1 mRNA stability and thus suggest a ferroptosis-related therapeutic option for YTHDC1high lung cancer.

Two R2R3-MYB transcription factors from Chinese cedar (Cryptomeria fortunei Hooibrenk) are involved in the regulation of secondary cell wall formation.

As the most abundant renewable energy source, wood comprises the secondary cell wall (SCW). SCW biosynthesis involves lignin and cellulose deposition. Increasing studies have illustrated that R2R3-MYB transcription factors (TFs) play pivotal roles in affecting lignin accumulation and SCW formation. Nevertheless, the regulatory roles of R2R3-MYBs are still unresolved in Cryptomeria fortunei Hooibrenk cambium and wood formation. To dissect the potentials of CfMYBs, we successfully cloned and intensively studied the functions of CfMYB4 and CfMYB5 in SCW formation and abiotic stress response. They both contained the conserved MYB domain capable of forming a special structure that could bind to the core motifs of downstream genes. The phylogenetic tree implied that two CfMYBs clustered into different evolutionary branches. They were predominantly expressed in the stem and were localized to the nucleus. Furthermore, CfMYB4 functioned as an activator to enhance lignin and cellulose accumulation, and increase the SCW thickness by elevating the expression levels of SCW-related genes. By contrast, CfMYB5 negatively regulated lignin and cellulose biosynthesis, and decreased SCW formation by reducing the expression of SCW biosynthetic genes. Our data not only highlight the regulatory functions of CfMYBs in lignin deposition but also provide critical insights into the development of strategies for the genetic improvement of Cryptomeria fortunei wood biomass.

Topical Dihydroartemisinin Improves Wound Healing in Diabetic Mice.

Impaired skin wound healing is a common complication of diabetes mellitus. Angiogenesis is a critical step in wound healing because it allows oxygen and nutrients to reach the injured area, thereby promoting wound cell proliferation, re-epithelialisation, and collagen regeneration. However, the neovascularisation ability of patients with diabetes often decreases. Therefore, finding ways to improve diabetic angiogenesis is important for treating diabetic wounds that do not heal. To the best of our knowledge, it is unclear whether dihydroartemisinin (DHA) affects diabetic wounds. This study sought to determine how topical DHA affects the healing of diabetic wounds and how it is related to markers of angiogenesis. We topically applied DHA to full-thickness cutaneous lesions in a streptozotocin (STZ)-induced diabetic mouse model. Under a fluorescence microscope, the pathological morphology of the wound skin was observed, together with the positive expression of platelet endothelial cell adhesion molecule-1 (CD31) and vascular endothelial growth factor (VEGF). Western blotting was used to determine the CD31 and VEGF protein expression levels. The mRNA expression was determined using qualitative real-time polymerase chain reaction (qRT-PCR). We found that DHA can improve the expression of CD31 and VEGF, and accelerate wound healing in diabetic mice. We believe that DHA promotes angiogenesis, which is associated with increased VEGF signalling in vivo. Therefore, DHA can effectively accelerate the process of diabetic wound healing by promoting angiogenesis, implying that DHA may be used as a topical drug for the treatment of diabetic wounds.

Correlation of psoas major muscle morphology with function and clinical symptoms in patients with symptomatic multilevel lumbar spinal stenosis.

OBJECTIVE: This study was performed to quantify the morphological characteristics of the psoas major muscle in patients with symptomatic multilevel degenerative lumbar spinal stenosis (SMLSS) and assess the correlations of these morphological characteristics with function and clinical symptoms. METHODS: One hundred fourteen patients diagnosed with SMLSS (≥ 3 segments) were included. The patients' presenting symptoms were assessed with the Oswestry Disability Index (ODI), and visual analogue scale (VAS) scores were recorded. The morphology of the psoas major was evaluated at the L3/4 intervertebral disc level in three ways: by measuring (i) the psoas muscle mass index (PMI); (ii) the mean muscle attenuation (Hounsfield units, HU); and (iii) the morphologic change of the psoas major (mean ratios of the short axis to the long axis of the bilateral psoas major). RESULTS: Men had a higher PMI than women (p = 0.001). Patients with severe disability had a significantly lower PMI (p = 0.002) and muscle attenuation (p = 0.001). The PMI and muscle attenuation were significantly higher in the patients with no or mild back pain (both p < 0.001). In the univariable and multivariable analyses, a greater HU value was associated with a higher functional status as assessed by the ODI (p = 0.002), and a higher PMI was associated with less severe back pain as measured by the VAS score (p < 0.001). CONCLUSION: This study showed that muscle attenuation of psoas major positively correlated with the functional status and PMI negatively correlated with low back pain severity in patients diagnosed with SMLSS. Future prospective studies are needed to evaluate whether improvement in such muscle parameters through physiotherapy programs can alleviate the clinical symptoms and improve the functional status of patients with SMLSS.

Physiological and gene expression changes of Cryptomeria fortunei Hooibrenk families under heat stress.

Heat stress is one of the major abiotic stresses affecting plant growth and productivity. Cryptomeria fortunei (Chinese cedar) is an excellent timber and landscaping tree species in southern China thanks to its beautiful appearance, straight texture and ability to purify the air and improve the environment. In this study, we first screened 8 excellent C. fortunei families (#12, #21, #37, #38, #45, #46, #48, #54) in a second generation seed orchard. We then analyzed the electrolyte leakage (EL) and lethal temperature at 50% (LT50) values under heat stress, to identify the families with the best heat resistance (#48) and the lowest heat resistance (#45) and determine the physiological and morphological response of different threshold-resistance of C. fortune to heat stress. The relative conductivity of the C. fortunei families showed an increasing trend with increasing temperature, following an "S" curve, and the half-lethal temperature ranges between 39°C and 43.2°C. The activities of SOD and POD fluctuated in the early stage of stress but decreased after 37°C. We observed the changes in the cell ultrastructure at 43°C, and the mesophyll cell structure of #48 was less damaged than that of #45. Eight heat resistance gene, including CfAPX1, CfAPX2, CfHSP11, CfHSP21, CfHSP70, CfHSFA1a, CfHSFB2a and CfHSFB4, were all up-regulated in #45 and #48, and there were significant differences between #45 and #48 under different heat stress treatments. We found a significant difference in heat tolerance between #45 and #48, such that #48 shows higher heat tolerance capability and could be exploited in breeding programs. We conclude that the strongly heat-resistant family had a more stable physiological state and a wider range of heat stress adaptations.

A potassium-chloride co-transporter promotes tumor progression and castration resistance of prostate cancer through m6A reader YTHDC1.

SLC12A5, a neuron-specific potassium-chloride co-transporter, has been reported to promote tumor progression, however, the underlying mechanism remains unclear. Here we report that SLC12A5 functions as an oncogene to promote tumor progression and castration resistance of prostate cancer through the N6-methyladenosine (m6A) reader YTHDC1 and the transcription factor HOXB13. We have shown that the level of SLC12A5 was increased in prostate cancer, in comparison to its normal counterparts, and further elevated in castration-resistant prostate cancer (CRPC). The enhanced expression of SLC12A5 mRNA was associated with neuroendocrine prostate cancer (NEPC) progression and poor survival in prostate cancer. Furthermore, we demonstrated that SLC12A5 promoted the castration resistance development of prostate cancer in addition to the cell proliferation and migration. Interestingly, SLC12A5 was detected in the cell nucleus and formed a complex with nuclear m6A reader YTHDC1, which in turn upregulated HOXB13 to promote the prostate cancer progression. Therefore, our findings reveal a mechanism that how the potassium-chloride cotransporter SLC12A5 promotes the tumor progression and provide a therapeutic opportunity for prostate cancer to apply the neurological disorder drug SLC12A5 inhibitors.

Synthesis and Full Characterization of One Organometallic Polyoxometalate-Based Copper(I)-Alkene Complex.

An alkene-bridged thioether ligand (L) was designed and used for its first study within a polyoxometalate (POM) hybrid system, and a POM-based copper(I)-alkene compound [(CuIL)2(PVMoVI12O40)]·(CuIL) (1) was isolated and characterized by X-ray crystallography. A unique alkene-coordinating N(η2-C═C)N mode of L is observed, and the Cu centers are captured by σ2,π-L in a pocket fashion, giving birth to discrete [CuIL]+ cations and [(CuIL)2(PVMoVI12)]- anions. The ionic crystal exhibits solubility in aprotic polar solvents, and the electrospray ionization mass spectrometry is used to explore the nature of species present in the solution. It is found that the whole cluster [PVMoVI12]3- is completely present, and all the main peaks can be assigned to different charged fragments of the same parent cluster.

H2AFX might be a prognostic biomarker for hepatocellular carcinoma.

BACKGROUND: H2AFX can play a central role in DNA repair, replication, transcription regulation, and chromosomal stability. However, there is little research to explore the expression of H2AFX in cancers. Moreover, the correlation between the expression of H2AFX and tumor immunity, which affects the prognosis of hepatocellular carcinoma (HCC), is not clear. This article aimed to observe the correlation between H2AFX and tumor tissue infiltration biomarkers in HCC and its prognostic potential in HCC. METHOD: Oncomine and TIMER database were used to assess the expression level of H2AFX mRNA, and GEPIA and Kaplan-Meier databases were used to evaluate its prognostic potential. The TIMER database analyzed the relationship between h2afx expression level and tumor immune cell infiltration markers in liver cancer tissues. RESULTS: The results showed that H2AFX was overexpressed in tumor tissues than normal tissues in HCC via analysis, and its expression level was correlated with the survival rate of HCC. Moreover, the expression level of H2AFX was related to various immune biomarkers. These results show that overexpression of H2AFX would reflect the poor prognosis of HCC, and these would also reflect that the gene H2AFX can affect the infiltration of HCC immune cells and then play a role in regulating tumor immunity. CONCLUSION: Our study showed that the gene H2AFX might be a potential poor prognostic biomarker in HCC and might be involved in the infiltration of HCC immune cells.

Overexpression of CfICE1 from Cryptomeria fortunei Enhances Cold, Drought and Salt Stress in Poplar.

ICE1, a regulator of the cold-inducible transcriptome and freezing tolerance, is currently widely believed to be involved in plant resistance to cold stress. In this study, CfICE1 from Cryptomeria fortunei was transformed into poplar. Physiological indicators of transgenic, empty vector and wild-type poplar after abiotic stress (cold, drought and salt) were determined. Transgenic lines had a higher chlorophyll content, antioxidant enzyme activity and soluble protein content, as well as a lower malondialdehyde and hydrogen peroxide content. The ultrastructure of the plant was observed by transmission electron microscopy, and after stress, the cell structure of the transgenic line was more complete than that of the wild type. CfICE1 was upregulated in transgenic poplar trees after abiotic stress (cold, drought and salt). The CfICE1 transgenic plants improved plant resistance by regulating the CBF gene of poplar under cold and salt stress. In terms of plant responses to abiotic stress, this study showed that overexpression of CfICE1 improved the cold, drought and salt tolerance of poplars.

Androgen Metabolism and Response in Prostate Cancer Anti-Androgen Therapy Resistance.

All aspects of prostate cancer evolution are closely related to androgen levels and the status of the androgen receptor (AR). Almost all treatments target androgen metabolism pathways and AR, from castration-sensitive prostate cancer (CSPC) to castration-resistant prostate cancer (CRPC). Alterations in androgen metabolism and its response are one of the main reasons for prostate cancer drug resistance. In this review, we will introduce androgen metabolism, including how the androgen was synthesized, consumed, and responded to in healthy people and prostate cancer patients, and discuss how these alterations in androgen metabolism contribute to the resistance to anti-androgen therapy.

Transcriptome and Metabolome Analyses Reveal Differences in Terpenoid and Flavonoid Biosynthesis in Cryptomeria fortunei Needles Across Different Seasons.

Cryptomeria fortunei (Chinese cedar) has outstanding medicinal value due to its abundant flavonoid and terpenoid contents. The metabolite contents of C. fortunei needles differ across different seasons. However, the biosynthetic mechanism of these differentially synthesized metabolites (DSMs) is poorly understood. To improve our understanding of this process, we performed integrated non-targeted metabolomic liquid chromatography and gas chromatography mass spectrometry (LC-MS and GC-MS), and transcriptomic analyses of summer and winter needles. In winter, the C. fortunei needle ultrastructure was damaged, and the chlorophyll content and F v/F m were significantly (p < 0.05) reduced. Based on GC-MS and LC-MS, we obtained 106 and 413 DSMs, respectively; based on transcriptome analysis, we obtained a total of 41.17 Gb of clean data and assembled 33,063 unigenes, including 14,057 differentially expressed unigenes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that these DSMs/DEGs were significantly (p < 0.05) enriched in many biosynthesis pathways, such as terpenoids, photosynthates, and flavonoids. Integrated transcriptomic and metabonomic analyses showed that seasonal changes have the greatest impact on photosynthesis pathways, followed by terpenoid and flavonoid biosynthesis pathways. In summer Chinese cedar (SCC) needles, DXS, DXR, and ispH in the 2-methyl-pentaerythritol 4-phosphate (MEP) pathway and GGPS were highly expressed and promoted the accumulation of terpenoids, especially diterpenoids. In winter Chinese cedar (WCC) needles, 9 genes (HCT, CHS, CHI, F3H, F3'H, F3'5'H, FLS, DFR, and LAR) involved in flavonoid biosynthesis were highly expressed and promoted flavonoid accumulation. This study broadens our understanding of the metabolic and transcriptomic changes in C. fortunei needles caused by seasonal changes and provides a reference regarding the adaptive mechanisms of C. fortunei and the extraction of its metabolites.