Gut microbiota plays a significant role in gout.

With the development of social economy, the incidence of gout is increasing, which is closely related to people's increasingly rich diet. Eating a diet high in purine, fat, sugar and low-fibre for a long time further aggravates gout by affecting uric acid metabolism. The renal metabolism mechanism of uric acid has been thoroughly studied. To find a new treatment method for gout, increasing studies have recently been conducted on the mechanism of intestinal excretion, metabolism and absorption of uric acid. The most important research is the relationship between intestinal microbiota and the risk of gout. Gut microbiota represent bacteria that reside in a host's gastrointestinal tract. The composition of the gut microbiota is associated with protection against pathogen colonization and disease occurrence. This review focuses on how gut microbiota affects gout through uric acid and discusses the types of bacteria that may be involved in the occurrence and progression of gout. We also describe potential therapy for gout by restoring gut microbiota homeostasis and reducing uric acid levels. We hold the perspective that changing intestinal microbiota may become a vital method for effectively preventing or treating gout.

Thylakoid protein FPB1 synergistically cooperates with PAM68 to promote CP47 biogenesis and Photosystem II assembly.

In chloroplasts, insertion of proteins with multiple transmembrane domains (TMDs) into thylakoid membranes usually occurs in a co-translational manner. Here, we have characterized a thylakoid protein designated FPB1 (Facilitator of PsbB biogenesis1) which together with a previously reported factor PAM68 (Photosynthesis Affected Mutant68) is involved in assisting the biogenesis of CP47, a subunit of the Photosystem II (PSII) core. Analysis by ribosome profiling reveals increased ribosome stalling when the last TMD segment of CP47 emerges from the ribosomal tunnel in fpb1 and pam68. FPB1 interacts with PAM68 and both proteins coimmunoprecipitate with SecY/E and Alb3 as well as with some ribosomal components. Thus, our data indicate that, in coordination with the SecY/E translocon and the Alb3 integrase, FPB1 synergistically cooperates with PAM68 to facilitate the co-translational integration of the last two CP47 TMDs and the large loop between them into thylakoids and the PSII core complex.

The role of TGF-ß signaling in muscle atrophy, sarcopenia and cancer cachexia.

Skeletal muscle, comprising a significant proportion (40 to 50 percent) of total body weight in humans, plays a critical role in maintaining normal physiological conditions. Muscle atrophy occurs when the rate of protein degradation exceeds protein synthesis. Sarcopenia refers to age-related muscle atrophy, while cachexia represents a more complex form of muscle wasting associated with various diseases such as cancer, heart failure, and AIDS. Recent research has highlighted the involvement of signaling pathways, including IGF1-Akt-mTOR, MuRF1-MAFbx, and FOXO, in regulating the delicate balance between muscle protein synthesis and breakdown. Myostatin, a member of the TGF-ß superfamily, negatively regulates muscle growth and promotes muscle atrophy by activating Smad2 and Smad3. It also interacts with other signaling pathways in cachexia and sarcopenia. Inhibition of myostatin has emerged as a promising therapeutic approach for sarcopenia and cachexia. Additionally, other TGF-ß family members, such as TGF-ß1, activin A, and GDF11, have been implicated in the regulation of skeletal muscle mass. Furthermore, myostatin cooperates with these family members to impair muscle differentiation and contribute to muscle loss. This review provides an overview of the significance of myostatin and other TGF-ß signaling pathway members in muscular dystrophy, sarcopenia, and cachexia. It also discusses potential novel therapeutic strategies targeting myostatin and TGF-ß signaling for the treatment of muscle atrophy.

Comparison of a novel hand-held retractor-assisted transforaminal lumbar interbody fusion by the wiltse approach and posterior TLIF: a one-year prospective controlled study.

BACKGROUND: This study aims to compare the clinical outcomes and safety of a novel hand-held retractor system-assisted Wiltse TLIF with that P-TLIF and assess whether this hand-held retractor system assisted Wiltse TLIF can yield less paraspinal muscle injury. METHODS: 56 patients (P-TLIF: 26, Wiltse TLIF: 30) were included in this one year prospective controlled study. The operation time, intraoperative blood loss, postoperative drainage, mobilization time, and discharge time were recorded. The clinical outcomes were evaluated by ODI, VAS, JOA, and SF-36 scores (7 days, 3, 6, and 12 months after surgery). Paraspinal muscle injury was assessed by postoperative MRI (6 months after surgery). CK and C-reaction protein were measured pre and postoperatively, and CT or X-ray (one year postoperatively) was used to assess bony union/non-union. RESULTS: The Wiltse (study) group was associated with significantly less estimated blood loss (79.67 ± 28.59 ml vs 192.31 ± 59.48 ml, P = 0.000*), postoperative drainage (43.33 ± 27.89 ml vs 285.57 ± 123.05 ml, P = 0.000*), and shorter mobilization (4.1 ± 1.2 d vs. 3.0 ± 0.9 d, P < 0.05) and discharge times (7.7 ± 1.9 d vs. 6.1 ± 1.2 d, P = 0.002*) than the P-TLIF (control) group. Serum CK activity at 24 h postoperatively in the study group was significantly lower than in the control group (384.10 ± 141.99 U/L vs 532.76 ± 225.76 U/L, P = 0.018*). At 7 days after surgery, VAS (2.3 ± 0.6 vs 3.2 ± 0.7, P = 0.000*)and ODI scores (43.9 ± 11.9 vs 55.2 ± 12.9, P = 0.001*) were lower, while the JOA scores (18.4 ± 3.4 vs 16.3 ± 4.2, P = 0.041*) was higher in the control group than in the study group. Results observed at 3 months of follow-up were consistent with those at 7 days. After six months postoperatively, paraspinal muscle degeneration in the control group was more significant than in the study group (P = 0.008*). CONCLUSION: Our study showed that this novel hand-held retractor system assisted Wiltse approach TLIF can significantly reduce paraspinal muscle injury, postoperative drainage, and intraoperative blood loss, mobilization and discharge time, as well as yield better short-term outcomes compared to P-TLIF. TRIAL REGISTRATION: 25/09/2023 NCT06052579.

Engineered the Active Site of ω-Transaminase for Enhanced Asymmetric Synthesis Towards (S)-1-[4-(Trifluoromethyl)phenyl]ethylamine.

ω-Transaminase (ω-TA) is a promising biocatalyst for the synthesis of chiral amines. In this study, a ω-TA derived from Vitreoscilla stercoraria DSM 513 (VsTA) was heterologous expressed in recombinant E. coli cells and applied to reduce 4'-(trifluoromethyl)acetophenone (TAP) to (S)-1-[4-(trifluoromethyl)phenyl]ethylamine ((S)-TPE), a pharmaceutical intermediate of chiral amine. Aimed to a more efficient synthesis of (S)-TPE, VsTA was further engineered via a semi-rational strategy. Compared to wild-type VsTA, the obtained R411A variant exhibited 2.39 times higher activity towards TAP and enhanced catalytic activities towards other prochiral aromatic ketones. Additionally, better thermal stability for R411A variant was observed with 25.4% and 16.3% increase in half-life at 30 °C and 40 °C, respectively. Structure-guided analysis revealed that the activity improvement of R411A variant was attributed to the introduction of residue A411, which is responsible for the increase in the hydrophobicity of substrate tunnel and the alleviation of steric hindrance, thereby facilitating the accessibility of hydrophobic substrate TAP to the active center of VsTA. This study provides an efficient strategy for the engineering of ω-TA based on semi-rational approach and has the potential for the molecular modification of other biocatalysts.

A Review of Emerging Technologies in Ultra-Smooth Surface Processing for Optical Components.

Advancements in astronomical telescopes and cutting-edge technologies, including deep ultraviolet (DUV) and extreme ultraviolet (EUV) lithography, have escalated demands and imposed stringent surface quality requirements on optical system components. Achieving near-ideal optical components requires ultra-smooth surfaces with sub-nanometer roughness, no sub-surface damage, minimal surface defects, low residual stresses, and intact lattice integrity. This necessity has driven the rapid development and diversification of ultra-smooth surface fabrication technologies. This paper summarizes recent advances in ultra-smooth surface processing technologies, categorized by their material removal mechanisms. A subsequent comparative analysis evaluates the roughness and polishing characteristics of ultra-smooth surfaces processed on various materials, including fused silica, monocrystalline silicon, silicon carbide, and sapphire. To maximize each process's advantages and achieve higher-quality surfaces, the paper discusses tailored processing methods and iterations for different materials. Finally, the paper anticipates future development trends in response to current challenges in ultra-smooth surface processing technology, providing a systematic reference for the study of the production of large-sized freeform surfaces.

CsMYB67 participates in the flavonoid biosynthesis of summer tea leaves.

Flavonoids are important compounds in tea leaves imparting bitter and astringent taste, which also play key roles in tea plants responding to environmental stress. Our previous study showed that the expression level of CsMYB67 was positively correlated with the accumulation of flavonoids in tea leaves as exposed to sunlight. Here, we newly reported the function of CsMYB67 in regulating flavonoid biosynthesis in tea leaves. CsMYB67 was localized in the nucleus and responded to temperature. The results of transient expression assays showed the co-transformation of CsMYB67 and CsTTG1 promoted the transcription of CsANS promoter in the tobacco system. CsTTG1 was bound to the promoter of CsANS based on the results of yeast one-hybrid (Y1H) and transient expression assays, while CsMYB67 enhanced the transcription of CsANS through protein interaction with CsTTG1 according to the results of yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC). Thus, CsMYB67-CsTTG1 module enhanced the anthocyanin biosynthesis through up-regulating the transcription of CsANS. Besides, CsMYB67 also enhanced the transcription of CsFLS and CsUFGT through forming transcription factor complexes. The function of CsMYB67 on flavonoid biosynthesis in tea leaves was validated by gene suppression assay. As CsMYB67 was suppressed, the transcriptional level of CsFLS was greatly reduced, leading to a significant increase in the contents of total catechins and total anthocyanidins. Hence, CsMYB67 plays an important role in regulating the downstream pathway of flavonoid biosynthesis in summer tea leaves.

Gibberellin promotes cambium reestablishment during secondary vascular tissue regeneration after girdling in an auxin-dependent manner in Populus.

Secondary vascular tissue (SVT) development and regeneration are regulated by phytohormones. In this study, we used an in vitro SVT regeneration system to demonstrate that gibberellin (GA) treatment significantly promotes auxin-induced cambium reestablishment. Altering GA content by overexpressing or knocking down ent-kaurene synthase (KS) affected secondary growth and SVT regeneration in poplar. The poplar DELLA gene GIBBERELLIC ACID INSENSITIVE (PtoGAI) is expressed in a specific pattern during secondary growth and cambium regeneration after girdling. Overexpression of PtoGAI disrupted poplar growth and inhibited cambium regeneration, and the inhibition of cambium regeneration could be partially restored by GA application. Further analysis of the PtaDR5:GUS transgenic plants, the localization of PIN-FORMED 1 (PIN1) and the expression of auxin-related genes found that an additional GA treatment could enhance the auxin response as well as the expression of PIN1, which mediates auxin transport during SVT regeneration. Taken together, these findings suggest that GA promotes cambium regeneration by stimulating auxin signal transduction.

Handelin alleviates cachexia- and aging-induced skeletal muscle atrophy by improving protein homeostasis and inhibiting inflammation.

BACKGROUND: Handelin is a bioactive compound from Chrysanthemum indicum L. that improves motor function and muscle integrity during aging in Caenorhabditis elegans. This study aimed to further evaluate the protective effects and molecular mechanisms of handelin in a mouse muscle atrophy model induced by cachexia and aging. METHODS: A tumour necrosis factor (TNF)-α-induced atrophy model was used to examine handelin activity in cultured C2C12 myotubes in vitro. Lipopolysaccharide (LPS)-treated 8-week-old model mice and 23-month-old (aged) mice were used to examine the therapeutic effects of handelin on cachexia- and aging-induced muscle atrophy, respectively, in vivo. Protein and mRNA expressions were analysed by Western blotting, ELISA and quantitative PCR, respectively. Skeletal muscle mass was measured by histological analysis. RESULTS: Handelin treatment resulted in an upregulation of protein levels of early (MyoD and myogenin) and late (myosin heavy chain, MyHC) differentiation markers in C2C12 myotubes (P < 0.05), and enhanced mitochondrial respiratory (P < 0.05). In TNF-α-induced myotube atrophy model, handelin maintained MyHC protein levels, increased insulin-like growth factor (Igf1) mRNA expression and phosphorylated protein kinase B protein levels (P < 0.05). Handelin also reduced atrogin-1 expression, inhibited nuclear factor-κB activation and reduced mRNA levels of interleukin (Il)6, Il1b and chemokine ligand 1 (Cxcl1) (P < 0.05). In LPS-treated mice, handelin increased body weight (P < 0.05), the weight (P < 0.01) and cross-sectional area (CSA) of the soleus muscle (P < 0.0001) and improved motor function (P < 0.05). In aged mice, handelin slightly increased the weight of the tibialis anterior muscle (P = 0.06) and CSA of the tibialis anterior and gastrocnemius muscles (P < 0.0001). In the tibialis anterior muscle of aged mice, handelin upregulated mRNA levels of Igf1 (P < 0.01), anti-inflammatory cytokine Il10 (P < 0.01), mitochondrial biogenesis genes (P < 0.05) and antioxidant-related enzymes (P < 0.05) and strengthened Sod and Cat enzyme activity (P < 0.05). Handelin also reduced lipid peroxidation and protein carbonylation, downregulated mRNA levels of Fbxo32, Mstn, Cxcl1, Il1b and Tnf (P < 0.05), and decreased IL-1ß levels in serum (P < 0.05). Knockdown of Hsp70 or using an Hsp70 inhibitor abolished the ameliorating effects of handelin on myotube atrophy. CONCLUSIONS: Handelin ameliorated cachexia- and aging-induced skeletal muscle atrophy in vitro and in vivo, by maintaining homeostasis of protein synthesis and degradation, possibly by inhibiting inflammation. Handelin is a potentially promising drug candidate for the treatment of muscle wasting.

The light-harvesting chlorophyll a/b-binding proteins of photosystem II family members are responsible for temperature sensitivity and leaf color phenotype in albino tea plant.

INTRODUCTION: Light-harvesting chlorophyll a/b-binding (LHCB) protein complexes of photosystem II are integral to the formation of thylakoid structure and the photosynthetic process. They play an important role in photoprotection, a crucial process in leaf development under low-temperature stress. Nonetheless, potential key genes directly related to low-temperature response and albino phenotype have not been precisely identified in tea plant. Moreover, there are no studies simultaneously investigating multiple albino tea cultivars with different temperature sensitivity. OBJECTIVES: The study aimed to clarify the basic characteristics of CsLHCB gene family members, and identify critical CsLHCB genes potentially influential in leaf color phenotypic variation and low-temperature stress response by contrasting green and albino tea cultivars. Concurrently, exploring the differential expression of the CsLHCB gene family across diverse temperature-sensitive albino tea cultivars. METHODS: We identified 20 putative CsLHCB genes according to phylogenetic analysis. Evolutionary relationships, gene duplication, chromosomal localization, and structures were analyzed by TBtools; the physiological and biochemical characteristics were analyzed by protein analysis websites; the differences in coding sequences and protein accumulation in green and albino tea cultivars, gene expression with maturity were tested by molecular biology technology; and protein interaction was analyzed in the STRING database. RESULTS: All genes were categorized into seven groups, mapping onto 7 chromosomes, including three tandem and one segmental duplications. They all own a conserved chlorophyll A/B binding protein domain. The expression of CsLHCB genes was tissue-specific, predominantly in leaves. CsLHCB5 may play a key role in the process of leaf maturation and senescence. In contrast to CsLHCB5, CsLHCB1.1, CsLHCB2, and CsLHCB3.2 were highly conserved in amino acid sequence between green and albino tea cultivars. In albino tea cultivars, unlike in green cultivars, the expression of CsLHCB1.1, CsLHCB1.2, and CsLHCB2 was down-regulated under low-temperature stress. The accumulation of CsLHCB1 and CsLHCB5 proteins was lower in albino tea cultivars. Greater accumulation of CsLHCB2 protein was detected in RX1 and RX2 compared to other albino cultivars. CONCLUSIONS: CsLHCB1.1, CsLHCB1.2, and CsLHCB2 played a role in the response to low-temperature stress. The amino acid sequence site mutation of CsLHCB5 would distinguish the green and albino tea cultivars. The less accumulation of CsLHCB1 and CsLHCB5 had a potential influence on albino leaves. Albino cultivars more sensitive to temperature exhibited lower CsLHCB gene expression. CsLHCB2 may serve as an indicator of temperature sensitivity differences in albino tea cultivars. This study could provide a reference for further studies of the functions of the CsLHCB family and contribute to research on the mechanism of the albino in tea plant.

Landscape and the immune patterns of cuproptosis in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma is an increasingly prevalent cancer type characterized by high incidence and mortality rates. Its early detection is challenging, primarily because of the absence of early molecular markers. Cuproptosis is a novel regulatory mechanism of cell death with implications in various cancers. In this study, we aimed to study cuproptosis-related genes in oral squamous cell carcinoma to identify their prognostic value. METHODS: By analyzing genomic, bulk RNA-seq, and single-cell RNA-seq data, we investigated 13 cuproptosis-related genes in The Cancer Genome Atlas-Oral Squamous Cell Carcinoma dataset and Gene Expression Omnibus repository (GSE172577). RESULTS: ATP7A, ATP7B, and DLST were the most frequently mutated genes, with nine of our studied genes associated with overall survival. Single-cell analysis was conducted to identify cuproptosis-related tumor cells in oral squamous cell carcinoma, which revealed two distinct patterns based on the expression of cuproptosis-related genes. These patterns exhibit differences in genetic alterations and tumor immune microenvironment. Finally, we developed a cuproptosis index using a random forest algorithm based on cuproptosis pattern-related genes in which higher levels were linked to poorer prognosis. CONCLUSION: Our findings provide valuable insights into the mechanisms underlying oral squamous cell carcinoma-associated cuproptosis.

The effect of different sources of mesenchymal stem cells on microglia states.

Microglial reaction plays a key role in the prognosis of traumatic CNS injuries (TBI and SCI). A growing number of studies have shown that mesenchymal stem cells (MSCs) play an important role in regulating microglial states. This review summarizes the effects and mechanisms of different sources of MSCs on microglial states in the last 5 years. In general, bone marrow-derived mesenchymal stem cells are the most accessible and widely used, and can produce immunosuppressive effects on a variety of brain injuries including TBI through tissue engineering in situ implantation; MSCs mainly regulate inflammatory pathways and promote the states of microglia in the anti-inflammatory direction, which also secrete certain cytokines or extracellular vesicles to affect apoptotic pathways, such as the extracellular vesicles miR-21-5p, acting as a neuronal protector.

The effects of gestational diabetes mellitus on fetal growth: is it different for low-risk and medium-high-risk pregnant women?

BACKGROUND: It has been suggested that gestational diabetes mellitus (GDM) alters the growth trajectory of a fetus and increases the risk of abnormal birth weight. In spite of this, there is still a significant debate regarding the mode and optimal timing of diagnosing this condition. Our aim was to determine fetal growth velocity and birth biometry in pregnant women with GDM at varying risk levels. METHODS: We conducted a cohort study involving 1023 pregnant women at a maternity hospital in Ma'anshan, China. All women completed an oral glucose tolerance test at 24-28 weeks' gestation. We measured fetal head circumference (HC), femoral length (FL), abdominal circumference (AC), biparietal diameter (BPD), and estimate fetal weight (EFW) by ultrasound at 17, 24, 31, and 35 weeks' gestation, respectively. RESULTS: Overall, 5115 ultrasound scans were performed. Among both low-risk and medium-high-risk pregnant women at 17-24 weeks' gestation, GDM exposure was associated with an increase in fetal growth velocity. Neonates born to women with GDM at medium-high risk had significantly larger birth weights than those born to women without GDM, while this was not observed in women at low risk. CONCLUSION: In medium-high-risk pregnant women, exposure to GDM has a greater effect on the fetus, leading to abnormal fetal growth velocity that lasts beyond week 24. It is evident from our results that the effects of GDM on fetal growth differ between medium-high-risk pregnant women and low-risk pregnant women, and therefore a different screening program based on the risk factor for GDM is warranted.

The modification of meteorological factors on the relationship between air pollution and periodontal diseases: an exploration based on different interaction strategies.

We aimed to characterize the association between air pollutants exposure and periodontal diseases outpatient visits and to explore the interactions between ambient air pollutants and meteorological factors. The outpatient visits data of several large stomatological and general hospitals in Hefei during 2015-2020 were collected to explore the relationship between daily air pollutants exposure and periodontal diseases by combining Poisson's generalized linear model (GLMs) and distributed lag nonlinear model (DLNMs). Subgroup analysis was performed to identify the vulnerability of different populations to air pollutants exposure. The interaction between air pollutants and meteorological factors was verified in both multiplicative and additive interaction models. An interquartile range (IQR) increased in nitrogen dioxide (NO2) concentration was associated with the greatest lag-specific relative risk (RR) of gingivitis at lag 3 days (RR = 1.087, 95% CI 1.008-1.173). Fine particulate matter (PM2.5) exposure also increased the risk of periodontitis at the day of exposure (RR = 1.049, 95% CI 1.004-1.096). Elderly patients with gingivitis and periodontitis were both vulnerable to PM2.5 exposure. The interaction analyses showed that exposure to high levels of NO2 at low temperatures was related to an increased risk of gingivitis, while exposure to high levels of NO2 and PM2.5 may also increase the risk of gingivitis and periodontitis in the high-humidity environment, respectively. This study supported that NO2 and PM2.5 exposure increased the risk of gingivitis and periodontitis outpatient visits, respectively. Besides, the adverse effects of air pollutants exposure on periodontal diseases may vary depending on ambient temperature and humidity.

Effect of gaseous pollutant and greenness exposure on mortality during treatment of newly treated tuberculosis patients: a provincial population-based cohort study.

BACKGROUND: Previous studies addressing the impact of environmental factors on TB prognosis are scarce, with only some studies examining the effect of particulate pollutants on TB mortality. Moreover, few studies have evaluated the effects of multiple gaseous pollutants and greenness exposures on newly treated TB patients on a large population scale. METHODS: Through the Centers for Disease Control and Prevention, data were collected from January 1, 2015 to December 31, 2020 for newly treated TB patients in Anhui Province, China. Data on gaseous pollutants sulfur dioxide, nitrogen dioxide, carbon monoxide, and ozone were collected through the National Earth System Science Data Center of China. Normalized vegetation index data were obtained through NASA. The Cox proportional risk model was also applied to calculate the hazard ratios of SO2, NO2, CO, O3, and NDVI with 95% confidence intervals for mortality among newly treated TB patients. RESULTS: Multifactorial Cox regression analysis showed that for every 0.10 µg/m3 increase in SO2, the risk of death among newly treated TB patients increased by 13.2% (HR = 1.132, 95% CI: 1.045-1.1.225), for every 10 µg/m3 increase in NO2, the risk of death among newly treated TB patients increased by 11.4%, and for each 0.1 mg/m3 increase in CO, the risk of death among newly treated TB patients increased by 5.8%. For each 0.1 increase in NDVI 250m-buffer and 500m-buffer, the risk of death among newly treated TB patients decreased by 8.5% and 6.4%, respectively. The effect of gaseous pollutants on mortality decreased progressively with elevated greenness exposure when greenness exposure was grouped from low to high. CONCLUSION: Gaseous pollutants are a risk factor during the treatment of newly treated TB patients and greenness exposure is a protective factor. Higher greenness exposure reduces the risk of death due to exposure to gaseous pollutants.

The expression of CD86 in CD3+CD56+ NKT cells is associated with the occurrence and prognosis of sepsis-associated encephalopathy in sepsis patients: a prospective observational cohort study.

The role of CD3+CD56+ natural killer T (NKT) cells and its co-signaling molecules in patients with sepsis-associated encephalopathy (SAE) is unknown. In this prospective observational cohort study, we initially recruited 260 septic patients and eventually analyzed 90 patients, of whom 57 were in the SAE group and 37 were in the non-SAE group. Compared to the non-SAE group, 28-day mortality was significantly increased in the SAE group (33.3% vs. 12.1%, p = 0.026), while the mean fluorescence intensity (MFI) of CD86 in CD3+CD56+ NKT cells was significantly lower (2065.8 (1625.5 ~ 3198.8) vs. 3117.8 (2278.1 ~ 5349), p = 0.007). Multivariate analysis showed that MFI of CD86 in NKT cells, APACHE II score, and serum albumin were independent risk factors for SAE. Furthermore, the Kaplan-Meier survival analysis indicated that the mortality rate was significantly higher in the high-risk group than in the low-risk group (χ2 = 14.779, p < 0.001). This study showed that the decreased expression of CD86 in CD3+CD56+ NKT cells is an independent risk factor of SAE; thus, a prediction model including MFI of CD86 in NKT cells, APACHE II score, and serum albumin can be constructed for diagnosing SAE and predicting prognosis.

Oncolytic virotherapy evolved into the fourth generation as tumor immunotherapy.

BACKGROUND: Oncolytic virotherapy (OVT) is a promising anti-tumor modality that utilizes oncolytic viruses (OVs) to preferentially attack cancers rather than normal tissues. With the understanding particularly in the characteristics of viruses and tumor cells, numerous innovative OVs have been engineered to conquer cancers, such as Talimogene Laherparepvec (T-VEC) and tasadenoturev (DNX-2401). However, the therapeutic safety and efficacy must be further optimized and balanced to ensure the superior safe and efficient OVT in clinics, and reasonable combination therapy strategies are also important challenges worthy to be explored. MAIN BODY: Here we provided a critical review of the development history and status of OVT, emphasizing the mechanisms of enhancing both safety and efficacy. We propose that oncolytic virotherapy has evolved into the fourth generation as tumor immunotherapy. Particularly, to arouse T cells by designing OVs expressing bi-specific T cell activator (BiTA) is a promising strategy of killing two birds with one stone. Amazing combination of therapeutic strategies of OVs and immune cells confers immense potential for managing cancers. Moreover, the attractive preclinical OVT addressed recently, and the OVT in clinical trials were systematically reviewed. CONCLUSION: OVs, which are advancing into clinical trials, are being envisioned as the frontier clinical anti-tumor agents coming soon.

Anthocyanin metabolism and its differential regulation in purple tea (Camellia sinensis).

Tea plants (Camellia sinensis) typically contain high-flavonoid phytochemicals like catechins. Recently, new tea cultivars with unique purple-colored leaves have gained attention. These purple tea cultivars are enriched with anthocyanin, which provides an interesting perspective for studying the metabolic flux of the flavonoid pathway. An increasing number of studies are focusing on the leaf color formation of purple tea and this review aims to summarize the latest progress made on the composition and accumulation of anthocyanins in tea plants. In addition, the regulation mechanism in its synthesis will be discussed and a hypothetical regulation model for leaf color transformation during growth will be proposed. Some novel insights are presented to facilitate future in-depth studies of purple tea to provide a theoretical basis for targeted breeding programs in leaf color.

Proteogenomics of clear cell renal cell carcinoma response to tyrosine kinase inhibitor.

The tyrosine kinase inhibitor (TKI) Sunitinib is one the therapies approved for advanced renal cell carcinoma. Here, we undertake proteogenomic profiling of 115 tumors from patients with clear cell renal cell carcinoma (ccRCC) undergoing Sunitinib treatment and reveal the molecular basis of differential clinical outcomes with TKI therapy. We find that chromosome 7q gain-induced mTOR signaling activation is associated with poor therapeutic outcomes with Sunitinib treatment, whereas the aristolochic acid signature and VHL mutation synergistically caused enhanced glycolysis is correlated with better prognosis. The proteomic and phosphoproteomic analysis further highlights the responsibility of mTOR signaling for non-response to Sunitinib. Immune landscape characterization reveals diverse tumor microenvironment subsets in ccRCC. Finally, we construct a multi-omics classifier that can detect responder and non-responder patients (receiver operating characteristic-area under the curve, 0.98). Our study highlights associations between ccRCC molecular characteristics and the response to TKI, which can facilitate future improvement of therapeutic responses.