Correlation of in vitro cell viability and cumulative singlet oxygen luminescence from protoporphyrin IX in mitochondria and plasma membrane.

SIGNIFICANCE: Photodynamic therapy (PDT) can be targeted toward different subcellular localizations, and it is proposed that different subcellular targets vary in their sensitivity to photobiological damage. Since singlet oxygen (1O2) has a very short lifetime with a limited diffusion length in cellular environments, measurement of cumulative 1O2 luminescence is the most direct approach to compare the PDT sensitivity of mitochondria and plasma membrane. APPROACH: PDT-generated near-infrared 1O2 luminescence at 1270 nm was measured together with cell viability for 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) and exogenous PpIX, at different incubation times. Confocal fluorescence microscopy indicated that ALA-induced PpIX (2 h) localized in the mitochondria, whereas exogenous PpIX (1 h) mainly localized to the plasma membrane. Cell viability was determined at several time points during PDT treatments using colony-forming assays, and the surviving fraction correlated well with cumulative 1O2 luminescence counts from PpIX in mitochondria and plasmas membrane, respectively. RESULTS: The mitochondria are more sensitive than the plasma membrane by a factor of 1.7. CONCLUSIONS: Direct 1O2 luminescence dosimetry's potential value for comparing the PDT sensitivity of different subcellular organelles was demonstrated. This could be useful for developing subcellular targeted novel photosensitizers to enhance PDT efficiency.

Unlocking the anticancer activity of gambogic acid: a shift towards ferroptosis via a GSH/Trx dual antioxidant system.

Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in ferroptosis by regulating the cellular antioxidant response and maintaining redox balance. However, compounds that induce ferroptosis through dual antioxidant pathways based on Nrf2 have not been fully explored. In our study, we investigated the impact of Gambogic acid (GA) on MCF-7 cells and HepG2 cells in vitro. The cytotoxicity, colony formation assay and cell cycle assay demonstrated potent tumor-killing ability of GA, while its effect was rescued by ferroptosis inhibitors. Furthermore, RNA sequencing revealed the enrichment of ferroptosis pathway mediated by GA. In terms of ferroptosis indicators detection, evidences for GA were provided including reactive oxygen species (ROS) accumulation, alteration in mitochondrial membrane potential (MMP), disappearance of mitochondrial cristae, lipid peroxidation induction, malondialdehyde (MDA) accumulation promotion, iron ion accumulation as well as glutathione (GSH)/thioredoxin (Trx) depletion. Notably, Ferrostatin-1 (Fer-1) and Liproxstatin-1 (Lip-1) successfully rescued GA-induced MDA accumulation. In terms of mechanism, Nrf2 was found to play a pivotal role in GA-induced ferroptosis by inducing protein alterations through the iron metabolism pathway and GSH/Trx dual antioxidant pathway. Furthermore, GA exerted good antitumor activity in vivo through GSH/Trx dual antioxidant pathway, and Fer-1 significantly attenuated its efficacy. In conclusion, our findings first provided new evidence for GA as an inducer of ferroptosis, and Nrf2-mediated GSH/Trx dual antioxidant system played an important role in GA-induced ferroptosis.

Suppressing the Thermal Quenching Effect via a Cluster Conformer in Copper(I)-Iodide Coordination Polymeric Phosphors for High-Power White LED Lighting.

High-power LED lighting is a crucial challenge due to the notorious thermal quenching (TQ) effect of traditional phosphors at high operating currents, which would result in poor device performance and hamper practical optoelectronic application. Herein, we demonstrate ligand engineering of a cubane- versus staircase-like [Cu4I4] conformer as a node in coordination polymers, which remarkably suppresses the TQ effect of cluster-based photoluminescence. For complex 1 (the formula [Cu4I4(bbimb)2]n) with the cubane-like [Cu4I4] conformer as a node, the metallophilicity interaction enables ultrabright triplet emission with a photoluminescence quantum yield over 82%, and the phonon-assisted detrapping process of excitons effectively suppresses the TQ effect in the wide temperature range. In contrast, the staircase-like [Cu4I4] conformer as a node in complex 2 (the formula [Cu4I4(bbtmb)2]n) exhibits a serious TQ effect over the investigated temperature. Phosphor-converted white LEDs (pc-wLEDs) were fabricated by integrating the cluster-based coordination polymers as a color converter, and their electroluminescence performances were investigated under high bias currents. The prototype pc-wLED device by incorporating the phosphor with the suppressed TQ effect exhibits a continuous rise in brightness under a high bias current of 300 mA. The results demonstrate that ligand engineering of the cluster conformer via suppressing the TQ effect proves efficient in designing an ideal color converter for high-power pc-wLED lighting.

Quantitative Imaging for Predicting Hematoma Expansion in Intracerebral Hemorrhage: A Multimodel Comparison.

BACKGROUND: Several studies report that radiomics provides additional information for predicting hematoma expansion in intracerebral hemorrhage (ICH). However, the comparison of diagnostic performance of radiomics for predicting revised hematoma expansion (RHE) remains unclear. METHODS: The cohort comprised 312 consecutive patients with ICH. A total of 1106 radiomics features from seven categories were extracted using Python software. Support vector machines achieved the best performance in both the training and validation datasets. Clinical factors models were constructed to predict RHE. Receiver operating characteristic curve analysis was used to assess the abilities of non-contrast computed tomography (NCCT) signs, radiomics features, and combined models to predict RHE. RESULTS: We finally selected the top 21 features for predicting RHE. After univariate analysis, 4 clinical factors and 5 NCCT signs were selected for inclusion in the prediction models. In the training and validation dataset, radiomics features had a higher predictive value for RHE (AUC = 0.83) than a single NCCT sign and expansion-prone hematoma. The combined prediction model including radiomics features, clinical factors, and NCCT signs achieved higher predictive performances for RHE (AUC = 0.88) than other combined models. CONCLUSIONS: NCCT radiomics features have a good degree of discrimination for predicting RHE in ICH patients. Combined prediction models that include quantitative imaging significantly improve the prediction of RHE, which may assist in the risk stratification of ICH patients for anti-expansion treatments.

[The role of ROS/JNK/caspase 3 axis in apoptosis induction by menthol-favored electronic cigarette liquid in human periodontal ligament stem cells].

PURPOSE: To explore the cytotoxic effect of a menthol-favored E-liquid on human periodontal ligament stem cells (hPDLSCs), as well as the underlying mechanism of electronic cigarette (E-cig)-induced cell apoptosis. METHODS: PDLSCs were isolated and cultured from periodontal ligament tissues of healthy premolars extracted for orthodontic reasons. Cells in passage 3 were used to detect the surface markers of stem cells by flow cytometry. Then the cells were exposed to different doses of menthol-favored E-liquid (at 59 mg/L nicotine concentration) in the culture median (the final nicotine concentrations were 0.1 µg/mL, 1.0 µg/mL, 10 µg/mL, 50 µg/mL, 0.1 mg/mL, 0.2 mg/mL and 0.5 mg/mL, respectively) for different period of times (24, 48 and 72 h). The cell viability was analyzed by CCK-8 assay. Cell apoptosis was evaluated by flow cytometry (7-AAD and Annexin V staining) and TUNEL assay. Reactive oxygen species (ROS) production was detected with fluorescence probe DCFH-DA by confocal microscopy and flow cytometry. The protein expression levels associated with ROS/JNK/caspase 3 axis(p-JNK, JNK, c-Jun, p-c-Jun, Bcl-2, Bax and cleaved-caspase 3) were analyzed by Western blot. Immunocytofluorescense staining was applied to evaluate the expression level of p-JNK. After addition of NAC, a ROS scavenger, and MAPK/JNK specific blocker SP600125, their effects on E-cig-induced cell apoptosis were evaluated. Statistical analysis was performed with Graph Pad 5.0 software package. RESULTS: Human PDLSCs were successfully isolated and cultured and flow cytometry assay showed the mesenchymal stem cell surface biomarkers (CD73, CD90 and CD105) were positively expressed. CCK8 assay indicated cell viability was significantly(P＜0.001) different among all concentration groups at various time points (24, 48 or 72 h), and the difference in apoptosis rate among all concentration groups was also statistically significant (P＜0.001). After exposure to E-liquid with nicotine concentration ≥50 µg/mL, cell viability was significantly reduced, and the proportion of apoptotic cells and the cellular ROS level was significantly increased in a dose-dependent manner as compared with the control group(0.0 mg/mL). Western blot assay showed E-cig exposure could promote MAPK/JNK phosphorylation in a dose-dependent and time-dependent manner. Either NAC or SP600125 could partially rescue the E-cig-induced cell apoptosis via reversing up-regulation of p-JNK and cleaved caspase 3. CONCLUSIONS: ROS/JNK/caspase 3 axis is involved in menthol-favored E-liquid-induced apoptosis of hPDLSCs.

Blue-shifted genetically encoded Ca2+ indicator with enhanced two-photon absorption.

Significance: Genetically encoded calcium ion (Ca2+) indicators (GECIs) are powerful tools for monitoring intracellular Ca2+ concentration changes in living cells and model organisms. In particular, GECIs have found particular utility for monitoring the transient increase of Ca2+ concentration that is associated with the neuronal action potential. However, the palette of highly optimized GECIs for imaging of neuronal activity remains relatively limited. Expanding the selection of available GECIs to include new colors and distinct photophysical properties could create new opportunities for in vitro and in vivo fluorescence imaging of neuronal activity. In particular, blue-shifted variants of GECIs are expected to have enhanced two-photon brightness, which would facilitate multiphoton microscopy. Aim: We describe the development and applications of T-GECO1-a high-performance blue-shifted GECI based on the Clavularia sp.-derived mTFP1. Approach: We use protein engineering and extensive directed evolution to develop T-GECO1. We characterize the purified protein and assess its performance in vitro using one-photon excitation in cultured rat hippocampal neurons, in vivo using one-photon excitation fiber photometry in mice, and ex vivo using two-photon Ca2+ imaging in hippocampal slices. Results: The Ca2+-bound state of T-GECO1 has an excitation peak maximum of 468 nm, an emission peak maximum of 500 nm, an extinction coefficient of 49,300 M-1 cm-1, a quantum yield of 0.83, and two-photon brightness approximately double that of EGFP. The Ca2+-dependent fluorescence increase is 15-fold, and the apparent Kd for Ca2+ is 82 nM. With two-photon excitation conditions at 850 nm, T-GECO1 consistently enabled the detection of action potentials with higher signal-to-noise (SNR) than a late generation GCaMP variant. Conclusions: T-GECO1 is a high-performance blue-shifted GECI that, under two-photon excitation conditions, provides advantages relative to late generation GCaMP variants.

Rescue of cardiac dysfunction during chemotherapy in acute myeloid leukaemia by blocking IL-1α.

BACKGROUND AND AIMS: Patients with acute myeloid leukaemia (AML) suffer from severe myocardial injury during daunorubicin (DNR)-based chemotherapy and are at high risk of cardiac mortality. The crosstalk between tumour cells and cardiomyocytes might play an important role in chemotherapy-related cardiotoxicity, but this has yet to be demonstrated. This study aimed to identify its underlying mechanism and explore potential therapeutic targets. METHODS: Cardiac tissues were harvested from an AML patient after DNR-based chemotherapy and were subjected to single-nucleus RNA sequencing. Cardiac metabolism and function were evaluated in AML mice after DNR treatment by using positron emission tomography, magnetic resonance imaging, and stable-isotope tracing metabolomics. Plasma cytokines were screened in AML mice after DNR treatment. Genetically modified mice and cell lines were used to validate the central role of the identified cytokine and explore its downstream effectors. RESULTS: In the AML patient, disruption of cardiac metabolic homeostasis was associated with heart dysfunction after DNR-based chemotherapy. In AML mice, cardiac fatty acid utilization was attenuated, resulting in cardiac dysfunction after DNR treatment, but these phenotypes were not observed in similarly treated tumour-free mice. Furthermore, tumour cell-derived interleukin (IL)-1α was identified as a primary factor leading to DNR-induced cardiac dysfunction and administration of an anti-IL-1α neutralizing antibody could improve cardiac functions in AML mice after DNR treatment. CONCLUSIONS: This study revealed that crosstalk between tumour cells and cardiomyocytes during chemotherapy could disturb cardiac energy metabolism and impair heart function. IL-1α neutralizing antibody treatment is a promising strategy for alleviating chemotherapy-induced cardiotoxicity in AML patients.

KTN1 mediated unfolded protein response protects keratinocytes from ionizing radiation-induced DNA damage.

BACKGROUND: The unfolded protein response (UPR) is one of the cytoprotective mechanisms against various stresses and essential for the normal function of skin. Skin injury caused by ionizing radiation (IR) is a common side effect of radiotherapy and it is unclear how UPR affects IR-induced skin injury. OBJECTIVES: To verify the effect of UPR on IR-induced DNA damage in keratinocytes and the relation between an endoplasmic reticulum (ER) protein KTN1 and UPR. METHODS: All experiments were performed on keratinocytes models: HaCaT and HEK-A. ER lumen and the expression levels of KTN1 and UPR pathway proteins (PERK, IRE1α and ATF6) were examined by transmission electron microscopy and immunoblotting, respectively. 4-PBA, an UPR inhibitor, was used to detected its effects on DNA damage and cell proliferation. Subsequently, the effects of KTN1 deletion on UPR, DNA damage and cell proliferation after IR were detected. Tunicamycin was used to reactivate UPR and then we examined its effects on DNA damage. RESULTS: UPR was activated by IR in keratinocytes. Inhibition of UPR aggravated DNA damage and suppressed cell proliferation after IR. KTN1 expression was upregulated by IR and KTN1 depletion reduced ER expansion and the expression of UPR-related proteins. Moreover, KTN1 depletion aggravated DNA damage and suppressed cell proliferation after IR could reversed by reactivation of UPR. CONCLUSION: KTN1 deletion aggravates IR-induced keratinocyte DNA damage via inhibiting UPR. Our findings provide new insights into the mechanisms of keratinocytes in response to IR-induced damage.

Will partial splenic embolization followed by splenectomy increase intraoperative bleeding?

BACKGROUND: Partial splenic embolization (PSE) has been suggested as an alternative to splenectomy in the treatment of hypersplenism. However, some patients may experience recurrence of hypersplenism after PSE and require splenectomy. Currently, there is a lack of evidence-based medical support regarding whether preoperative PSE followed by splenectomy can reduce the incidence of complications. AIM: To investigate the safety and therapeutic efficacy of preoperative PSE followed by splenectomy in patients with cirrhosis and hypersplenism. METHODS: Between January 2010 and December 2021, 321 consecutive patients with cirrhosis and hypersplenism underwent splenectomy at our department. Based on whether PSE was performed prior to splenectomy, the patients were divided into two groups: PSE group (n = 40) and non-PSE group (n = 281). Patient characteristics, postoperative complications, and follow-up data were compared between groups. Propensity score matching (PSM) was conducted, and univariable and multivariable analyses were used to establish a nomogram predictive model for intraoperative bleeding (IB). The receiver operating characteristic curve, Hosmer-Lemeshow goodness-of-fit test, and decision curve analysis (DCA) were employed to evaluate the differentiation, calibration, and clinical performance of the model. RESULTS: After PSM, the non-PSE group showed significant reductions in hospital stay, intraoperative blood loss, and operation time (all P = 0.00). Multivariate analysis revealed that spleen length, portal vein diameter, splenic vein diameter, and history of PSE were independent predictive factors for IB. A nomogram predictive model of IB was constructed, and DCA demonstrated the clinical utility of this model. Both groups exhibited similar results in terms of overall survival during the follow-up period. CONCLUSION: Preoperative PSE followed by splenectomy may increase the incidence of IB and a nomogram-based prediction model can predict the occurrence of IB.

Efficacy and safety of Wuhu oral liquid in treating acute soft tissue injuries: a multicenter, randomized, double-blind, double-dummy, parallel-controlled trial.

Background: Wuhu Oral Liquid (WHOL) is a modified preparation derived from the famous Wuhu Powder, which has a long history of use in treating traumatic injuries. This preparation has anti-inflammatory and analgesic properties and accelerates recovery following acute soft tissue injuries. Aims: To evaluate the efficacy and safety of WHOL in treating acute soft tissue injury associated with qi stagnation and blood stasis syndrome and to provide a basis for applying for the protection of varieties of Chinese medicine for WHOL. Methods: This study was a randomized, controlled, double-blind, multicenter clinical trial in which Fufang Shang Tong Capsule (FFSTC) was selected as the control drug. A total of 480 subjects with acute soft tissue injury associated with qi stagnation and blood stasis syndrome were randomly divided into a test and control group in a 3:1 ratio. The duration of drug treatment was 10 days. The primary outcome was Visual Analogue Scale (VAS) score for pain (including pain at rest and pain on activity). Secondary outcomes included the disappearance time of the pain at rest and on activity; the curative effect of TCM syndrome and improvement in the individual symptoms of TCM (swelling, ecchymosis, and dysfunction); and changes in C-reactive protein (CRP) and interleukin-6 (IL-6) levels. Safety was assessed using vital signs, laboratory examinations, electrocardiograms, and physical examinations. Results: Patient compliance was satisfactory in both groups (all between 80% and 120%). After 4 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the VAS scores for pain at rest (-1.88 ± 1.13 vs. -1.60 ± 0.93, p < 0.05) and on activity (-2.16 ± 1.18 vs. -1.80 ± 1.07, p < 0.05). After 7 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the VAS scores for pain on activity (-3.87 ± 1.60 vs. -3.35 ± 1.30, p < 0.01) and improving swelling (cure rate: 60.4% vs. 46.2%, p < 0.05; obvious effective rate: 60.7% vs. 47.0%, p < 0.05). After 10 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the levels of CRP (-0.13 ± 2.85 vs. 0.25 ± 2.09, p < 0.05) and improving the TCM syndrome (cure rate: 44.1% vs. 30.8%, p < 0.05) and swelling (cure rate: 75.6% vs. 67.5%, p < 0.01; obvious effective rate: 75.6% vs. 68.4%, p < 0.05; effective rate: 77.0% vs. 71.8%, p < 0.05). The disappearance time of pain at rest was 8 days in both groups and 9 days on activity in both groups. In addition, there was no statistical difference between the incidence of adverse events (4.5% vs. 2.6%, p > 0.05) and adverse reactions (0.3% vs. 0%, p > 0.05) between the WHOL group and the FFSTC group. No serious adverse events occurred in either group, and no subjects were withdrawn because of adverse events. Conclusion: WHOL relieves the symptoms caused by acute soft tissue injury associated with qi stagnation and blood stasis syndrome more rapidly than FFSTC, and it is effective and safe in the treatment of acute soft tissue injury. Future studies still need a larger sample size to verify its efficacy and safety. Clinical Trial Registration: https:// www.chictr.org.cn/showproj.html?proj=149531, Identifier ChiCTR2200056411.

Chromosome ends initiate homologous chromosome pairing during rice meiosis.

During meiotic prophase I, chromosomes undergo large-scale dynamics to allow homologous chromosome pairing, prior to which chromosome ends attach to the inner nuclear envelope and form a chromosomal bouquet. Chromosome pairing is crucial for homologous recombination and accurate chromosome segregation during meiosis. However, the specific mechanism by which homologous chromosomes recognize each other is poorly understood. Here, we investigated the process of homologous chromosome pairing during early prophase I of meiosis in rice (Oryza sativa) using pooled oligo probes specific to an entire chromosome or chromosome arm. We revealed that chromosome pairing begins from both ends and extends towards the center from early zygotene through late zygotene. Genetic analysis of both trisomy and autotetraploidy also showed that pairing initiation is induced by both ends of a chromosome. However, healed ends that lack the original terminal regions on telocentric and acrocentric chromosomes cannot initiate homologous chromosome pairing, even though they may still enter the telomere clustering region at the bouquet stage. Furthermore, a chromosome that lacks the distal parts on both sides loses the ability to pair with other intact chromosomes. Thus, the native ends of chromosomes play a crucial role in initiating homologous chromosome pairing during meiosis and likely have a substantial impact on genome differentiation.

Corrigendum: Identification of ACKR4 as an immune checkpoint in pulmonary arterial hypertension.

[This corrects the article DOI: 10.3389/fimmu.2023.1153573.].

RETINOBLASTOMA RELATED 1 switches mitosis to meiosis in rice.

The transition from mitosis to meiosis is a critical event in the reproductive development of all sexually reproducing species. However, the mechanisms that regulate this process in plants remain largely unknown. Here, we find that the rice (Oryza sativa L.) protein RETINOBLASTOMA RELATED 1 (RBR1) is essential to the transition from mitosis to meiosis. Loss of RBR1 function results in hyper-proliferative sporogenous-cell-like cells (SCLs) in the anther locules during early stages of reproductive development. These hyper-proliferative SCLs are unable to initiate meiosis, eventually stagnating and degrading at late developmental stages to form pollen-free anthers. These results suggest that RBR1 acts as a gatekeeper of entry into meiosis. Furthermore, cytokinin content is significantly increased in rbr1 mutants, whereas the expression of type-B response factors, particularly LEPTO1, is significantly reduced. Given the known close association of cytokinins with cell proliferation, these findings imply that hyper-proliferative germ cells in the anther locules may be attributed to elevated cytokinin concentrations and disruptions in the cytokinin pathway. Using a genetic strategy, the association between germ cell hyper-proliferation and disturbed cytokinin signaling in rbr1 has been confirmed. In summary, we reveal a unique role of RBR1 in the initiation of meiosis; our results clearly demonstrate that the RBR1 regulatory module is connected to the cytokinin signaling pathway and switches mitosis to meiosis in rice.

Identification of clinical characteristics biomarkers for rheumatoid arthritis through targeted DNA methylation sequencing.

OBJECTIVES: Rheumatoid arthritis (RA) is a complex disease with a challenging diagnosis, especially in seronegative patients. The aim of this study is to investigate whether the methylation sites associated with the overall immune response in RA can assist in clinical diagnosis, using targeted methylation sequencing technology on peripheral venous blood samples. METHODS: The study enrolled 241 RA patients, 30 osteoarthritis patients (OA), and 30 healthy volunteers control (HC). Fifty significant cytosine guanine (CG) sites between undifferentiated arthritis and RA were selected and analyzed using targeted DNA methylation sequencing. Logistic regression models were used to establish diagnostic models for different clinical features of RA, and six machine learning methods (logit model, random forest, support vector machine, adaboost, naive bayes, and learning vector quantization) were used to construct clinical diagnostic models for different subtypes of RA. Least absolute shrinkage and selection operator regression and detrended correspondence analysis were utilized to screen for important CGs. Spearman correlation was used to calculate the correlation coefficient. RESULTS: The study identified 16 important CG sites, including tumor necrosis factort receptor associated factor 5 (TRAF5) (chr1:211500151), mothers against decapentaplegic homolog 3 (SMAD3) (chr15:67357339), tumor endothelial marker 1 (CD248) (chr11:66083766), lysosomal trafficking regulator (LYST) (chr1:235998714), PR domain zinc finger protein 16 (PRDM16) (chr1:3307069), A-kinase anchoring protein 10 (AKAP10) (chr17:19850460), G protein subunit gamma 7 (GNG7) (chr19:2546620), yes1 associated transcriptional regulator (YAP1) (chr11:101980632), PRDM16 (chr1:3163969), histone deacetylase complex subunit sin3a (SIN3A) (chr15:75747445), prenylated rab acceptor protein 2 (ARL6IP5) (chr3:69134502), mitogen-activated protein kinase kinase kinase 4 (MAP3K4) (chr6:161412392), wnt family member 7A (WNT7A) (chr3:13895991), inhibin subunit beta B (INHBB) (chr2:121107018), deoxyribonucleic acid replication helicase/nuclease 2 (DNA2) (chr10:70231628) and chromosome 14 open reading frame 180 (C14orf180) (chr14:105055171). Seven CG sites showed abnormal changes between the three groups (P < 0.05), and 16 CG sites were significantly correlated with common clinical indicators (P < 0.05). Diagnostic models constructed using different CG sites had an area under the receiver operating characteristic curve (AUC) range of 0.64-0.78 for high-level clinical indicators of high clinical value, with specificity ranging from 0.42 to 0.77 and sensitivity ranging from 0.57 to 0.88. The AUC range for low-level clinical indicators of high clinical value was 0.63-0.72, with specificity ranging from 0.48 to 0.74 and sensitivity ranging from 0.72 to 0.88. Diagnostic models constructed using different CG sites showed good overall diagnostic accuracy for the four subtypes of RA, with an accuracy range of 0.61-0.96, a balanced accuracy range of 0.46-0.94, and an AUC range of 0.46-0.94. CONCLUSIONS: This study identified potential clinical diagnostic biomarkers for RA and provided novel insights into the diagnosis and subtyping of RA. The use of targeted deoxyribonucleic acid (DNA) methylation sequencing and machine learning methods for establishing diagnostic models for different clinical features and subtypes of RA is innovative and can improve the accuracy and efficiency of RA diagnosis.

Poly(3-Methylthiophene)/Graphene Composite Cathode for Rechargeable Aluminum-Ion Batteries.

To reduce the dependence on traditional fossil energy, developing efficient energy storage systems is urgent. The reserves of aluminum resources in the earth's crust are extremely rich, which makes aluminum-ion batteries a promising competitor of new energy storage devices. Here, we report a poly(3-methylthiophene)/graphene (P3TH/Graphene) composite as the cathode of an aluminum-ion battery. The adjustment of polymer chain spacing by the methyl side chain provides a channel conducive to the transport of large-size AlCl4- complexes. The addition of electron donor groups also changes the electron delocalization characteristics of polymers and improves the specific capacity of the material. At the same time, the in situ composite of graphene can enhance the Π-Π interaction to form a favorable electronic transmission channel. At a current density of 200 mA g-1, the P3TH/Graphene composite showed a specific capacity of ∼150 mA g-1. The flexible structure of the polymer also guarantees the excellent rate capability of the composite.

The Contribution of Double-strand Break Repair Radiation Sensitive Protein 51 Genotypes to Lung Cancer in Taiwan.

BACKGROUND/AIM: Numerous studies have reported the over-expression of the radiation-sensitive protein 51 (RAD51) in various types of cancer. However, the role of RAD51 genotypes in lung cancer remains largely unknown. This study aimed to assess the impact of the common variant RAD51 rs1801320 (G-135C) genotypes on the risk of lung cancer in Taiwan. MATERIALS AND METHODS: The contribution of RAD51 rs1801320 genotypes to lung cancer risk was investigated in a cohort comprising 358 lung cancer patients and 716 age- and sex-matched healthy controls, utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: The analysis revealed that among the control subjects, the percentages of GG, CG, and CC genotypes of RAD51 rs1801320 were 73.2%, 24.3%, and 2.5%, respectively. Among the lung cancer patients, these percentages were 71.0%, 25.1%, and 3.9%, respectively (p for trend=0.4075). Allelic frequency distributions showed no significant association between the C allele of RAD51 rs1801320 and lung cancer risk determination (p=0.2987). Specifically, the RAD51 rs1801320 CC genotypes were associated with an elevated risk of lung cancer among males [adjusted odds ratio (aOR)=2.28, 95% confidence interval (95%CI)=1.03-4.87] and smokers (aOR=2.93, 95%CI=1.23-5.87), but not among females and non-smokers. CONCLUSION: The RAD51 rs1801320 CC genotype was identified as a risk factor for elevated lung cancer risk in males and smokers. This genotype may serve as a molecular biomarker at the DNA level for early detection and prediction of lung cancer in Taiwan.

The association of cervical sagittal alignment with anterior bone loss following single-level anterior cervical surgery.

Background: Anterior bone loss (ABL) is a common phenomenon after cervical disc replacement (CDR), which can also be observed after anterior cervical discectomy and fusion (ACDF). This study aimed to investigate the incidence and severity of ABL in single-level CDR and ACDF and explore the association of cervical sagittal alignment with ABL. Methods: This is a single-center retrospective cohort study. A total of 113 patients treated with CDR and 99 patients treated with ACDF were retrospectively reviewed from January 2014 to December 2018 in West China Hospital. Radiological data were collected at pre-operation, 1 week, 3 months postoperatively, and the last follow-up. The incidence and severity of ABL after both CDR and ACDF were evaluated. Cervical sagittal alignment parameters, including C0-C2 angle, cervical lordosis (CL), C2-C7 sagittal vertical axis (cSVA), T1 slope, functional spinal unit angle, disc angle, and surgical level slope, were evaluated. Results: ABL was identified in 75 (66.4%) patients in the CDR group and 57 (57.6%) patients in the ACDF group. There were no significant differences in the incidence, severity, and location of ABL between the ACDF and CDR groups. For patients who underwent ACDF, the proportion of females was significantly higher in the ABL group (64.9% vs. 33.3%, P=0.002), whereas the body mass index (BMI) was significantly lower in the ABL group compared to the non-ABL group (22.72±3.09 vs. 24.60±3.04, P=0.002). No effect of ABL on the short-term clinical outcomes of ACDF and CDR was observed. In the ACDF group, patients with ABL had significantly smaller postoperative CL (11.83°±8.24° vs. 15.25°±8.32°, P=0.04) and cSVA (17.77±10.08 vs. 23.35±9.86 mm, P=0.007). In the CDR group, no significant differences were found in the cervical sagittal parameters between patients with and without ABL (CL: 12.58±8.70 vs. 15.46±8.50, P=0.10; cSVA: 20.95±8.54 vs. 19.40±9.43, P=0.38). Conclusions: ABL is common after both CDR and ACDF with comparable incidence and severity. Cervical sagittal alignment was closely related to ABL after ACDF yet had less influence on ABL after CDR.

A review of quantification methods for light absorption enhancement of black carbon aerosol.

Black carbon (BC) is a distinct type of carbonaceous aerosol that has a significant impact on the environment, human health, and climate. A non-BC material coating on BC can alter the mixing state of the BC particles, which considerably enhances the mass absorption efficiency of BC by directing more energy toward the BC cores (lensing effect). A lot of methods have been reported for quantifying the enhancement factor (Eabs), with diverse results. However, to the best of our knowledge, a comprehensive review specific to the quantification methods for Eabs has not been systematically performed, which is unfavorable for the evaluation of obtained results and subsequent radiative forcing. In this review, quantification methods are divided into two broad categories, direct and indirect, depending on whether experimental removal of the coating layer from an aged carbonaceous particle is required. The direct methods described include thermal peeling, solvent dissolution, and optical virtual exfoliation, while the indirect methods include intercept-linear regression fitting, minimum R squared, numerical simulation, and empirical value. We summarized the principles, procedures, virtues, and limitations of the major Eabs quantification methods and analyzed the current problems in the determination of Eabs. We pointed out what breakthroughs are needed to improve or innovate Eabs quantification methods, particularly regarding the need to avoid the influence of brown carbon, develop a broadband Eabs quantification scheme, quantify the Eabs values for the emissions of low-efficiency combustions, measure the Eabs of particles in a high-humidity environment, design a real-time monitor of Eabs by a proper combination of mature techniques, and make more use of artificial intelligence for better Eabs quantification. This review deepens the understanding of Eabs quantification methods and benefits the estimation of the contribution of BC to radiative forcing using climate models.

Anaphylactic deaths: A retrospective study of forensic autopsy cases from 2009 to 2019 in Shanghai, China.

Anaphylaxis is a rare but well-known cause of sudden unexpected death, although data from forensic autopsies in anaphylactic deaths are limited. Herein, a retrospective study of a series of allergic deaths from 2009 through 2019 in Shanghai, China, was conducted to investigate the demographic, medical, and forensic pathological characteristics of fatal anaphylaxis to improve medicolegal understanding on anaphylactic death. Sixty-two autopsy cases of anaphylactic death were registered in this study. Males dominated the cases (74.2%) against females (25.8%), with an average age of 38.8 years. Medications (98.4%), particularly antibiotics (72.6%), were the most frequent cause of anaphylaxis, and 44 cases (71.0%) occurred in clinics administered illegally by unlicensed clinicians. The anaphylactic symptoms began within a few minutes to less than 1 h in 53 cases, with dyspnea (56.5%) and sudden shock (46.8%) being the most common clinical signs. Thirty cases (48.4%) of anaphylaxis resulted in death within 1 h. Laryngeal edema and multiple tissue eosinophil infiltration (85.5%) were the most prevalent autopsy findings, followed by pulmonary edema and congestion (24.2%), which were considered to be non-specific but suggestive. The comorbidities were mainly cardiovascular disease (33.9%), pneumonia (8.1%) and asthma (8.1%). Serum IgE were measured in 11 of 62 cases, ranging from 43.3 to 591 IU/ml, severed as a helpful marker. Therefore, we suggested a thorough analysis of allergen exposure, clinical history and autopsy findings is required for the diagnosis of anaphylactic death currently.