Clinical characteristics and risk factors for ZF2001 fully vaccinated inpatients with COVID-19: A retrospective cohort study.

The ZF2001 vaccine has demonstrated high efficacy in preventing coronavirus disease 2019 (COVID-19). However, the clinical characteristics of breakthrough infections in vaccinated individuals and the risk factors for adverse outcomes in COVID-19 patients remain unclear. We conducted a retrospective single-center cohort study at Xiangya Hospital of Central South University, including 210 fully vaccinated COVID-19 inpatients from December 5, 2022, to January 31, 2023. Data on clinical characteristics, laboratory findings, disease severity, treatment, and prognosis were collected and analyzed. Our findings revealed that COVID-19 inpatients still experienced common symptoms at the onset of illness, but most laboratory findings were within the normal range, except for white blood cell count (WBC), lymphocyte count, and lactate dehydrogenase (LDH) levels. Following standard treatment, 95.7% of patients were discharged from the hospital. We identified seven variables significantly associated with a higher risk of adverse outcomes, including age over 65, elevated WBC count, reduced lymphocyte count, higher levels of blood urea nitrogen (BUN), LDH, troponin, D-dimer, and procalcitonin. This study supports the substantial clinical benefits of the ZF2001 vaccine for COVID-19 patients. Additionally, age over 65, elevated WBC count, reduced lymphocyte count, and higher blood levels of BUN, LDH, D-dimer, and procalcitonin may be used as predictive factors for disease progression in fully vaccinated COVID-19 inpatients.

Mn(II)-Based Metal Halide with Near-Unity Quantum Yield for White LEDs and High-Resolution X-ray Imaging.

Metal halides have drawn great interest as luminescent materials and scintillators due to their outstanding optical properties. Exploring new types of phosphors with easy production processes, excellent photophysical properties, high light yields, and environmentally friendly compositions is crucial and quite challenging. Herein, a novel Mn(II)-based metal halide (4-BTP)2MnBr4 was produced using a facile solvent evaporation method, which exhibited a strong green emission peaking at 524 nm from the d-d transition of tetrahedral-coordinated Mn2+ ion and a near-unity quantum yield. The prepared white light-emitting diode device has a wide color gamut of 100.7% NTSC with CIE chromaticity coordinates of (0.32, 0.32). In addition, (4-BTP)2MnBr4 demonstrates excellent characteristics in X-ray scintillation, including a high light yield of 98 000 photons/MeV, a sensitive detection limit of 37.4 nGy/s, excellent resistance to radiation damage, and successful demonstration of X-ray imaging with high resolution at 21.3 lp/mm, revealing the potential for application in diagnostic X-ray medical imaging and industry radiation detection.

Ultralong Red Room-Temperature Phosphorescence of 2D Organic-Inorganic Metal Halide Perovskites for Afterglow Red LEDs and X-ray Scintillation Applications.

Organic-inorganic metal hybrid perovskites (OIHPs) have emerged as a promising class of materials for next-generation optoelectronic applications. However, the realization of red and near-infrared (NIR) room-temperature phosphorescence (RTP) in these materials remains limited. In this study, a very strong red RTP emission centered at 610 nm is achieved by doping Mn2+ ions into Cd-based 2D OIHPs. Notably, the optimized B-EACC:Mn2+ exhibited a high quantum yield of 44.11%, an ultralong lifetime of up to 378 ms, and excellent stability against high temperatures and various solvents, surpassing most reported counterparts of 2D OIHPs. Moreover, the B-EACC:Mn2+ can be used as a red emitter for coating an ultraviolet light-emitting diode chip, exhibiting an observable afterglow to the naked eye for approximately 4 s. In addition, the B-EACC:Mn2+ demonstrates interesting characteristics under X-ray excitation, exhibiting X-ray response at radiation doses in the range of 34.75-278 µGy s-1. This work suggests the infinite possibility of doping guest ions to realize red RTP in 2D OIHPs, promoting the development of long-persistent phosphorescent emitters for multifunctional light-emitting applications.

Achieving Ultralong Room-Temperature Phosphorescence in Two-Dimensional Metal Halide Perovskites by Alkyl Chain Engineering.

Two-dimensional (2D) metal halide perovskites with highly efficient ultralong room-temperature phosphorescence (URTP) are rare due to their uncertain structures and complicated intermolecular interactions. Herein, by varying the alkyl length of organic units, we synthesized two single-component 2D metal hybrid perovskites, i.e., B-MACC and B-EACC, with obvious URTP emission. In particular, B-EACC exhibits a green-yellow URTP emission with an ultralong lifetime (579 ms) and a high efficiency (14.86%). It is found that the molecular packing of B-EA+ cations because of the presence one more carbon in the alkyl chain affords strong hydrogen bonding and π-π stacking interactions, which immobilizes and reduces the triplet exciton quenching. Moreover, B-MACC and B-EACC with space-time dual-resolved characteristics can be utilized for dynamic information encryption and optical logic gate applications. This study is the first to disclose the relation between the characteristics of molecular packing and the resultant URTP of 2D metal hybrid perovskites, significantly advancing the development of next-generation URTP materials for versatile applications.

Posterior-only debridement, internal fixation, and interbody fusion using titanium mesh in the surgical treatment of thoracolumbar tuberculosis with spinal epidural abscess: a minimum 5-year follow-up.

OBJECTIVE: To investigate the clinical efficacy and feasibility of posterior-only debridement, internal fixation, and interbody fusion using titanium mesh in the surgical treatment of thoracolumbar tuberculosis (TB) with spinal epidural abscess. METHODS: From January 2008 to January 2014, a total of 45 patients (27 male and 18 female) were reviewed. The patients were diagnosed with thoracolumbar TB with spinal epidural abscess. The patients underwent posterior-only debridement, internal fixation, and interbody fusion using titanium mesh. Hence, we assessed the intraoperative and postoperative complications, disease recurrences, kyphosis deformity correction, and neurological improvement following the American Spinal Injury Association (ASIA). We used SPSS 22.0 for the statistical analyses. An independent Student's t-test was used for the analysis of preoperative and postoperative continuous variables. The value of P (P < 0.05) was considered statistically significant. RESULTS: The mean age of patients was 37.76 ± 10.94 years (17-59 years). The mean follow-up time was 82.76 ± 12.56 months (60-128 months). The mean kyphosis Cobb angle preoperative was 29.36 ± 13.29° (5-55°) and postoperative was 3.58 ± 5.44° (- 6-13°), given the value of P (P < 0.001). According to the neurological score by the ASIA scale, there were 3 cases of grade B, 11 cases of grade C, 16 cases of grade D, and 15 cases of grade E preoperatively. The neurological score improved by 1 ~ 2 grades. All patients achieved pain relief and the VAS score significantly reduced at the last follow-up (P<0.05). While 1 patient had cerebrospinal fluid leakage, 1 had a neurological complication, 1 had delayed surgical wound healing, and 1 had a disease recurrence. No pseudoarthrosis or implant failure occurred in our patients. All patients achieved solid bone graft fusion. CONCLUSION: For thoracolumbar TB patients with spinal epidural abscess, posterior-only debridement, internal fixation, and interbody fusion using titanium mesh are safe and effective surgical treatments.

Smoking, DNA Methylation, and Breast Cancer: A Mendelian Randomization Study.

BACKGROUND: Smoking was strongly associated with breast cancer in previous studies. Whether smoking promotes breast cancer through DNA methylation remains unknown. METHODS: Two-sample Mendelian randomization (MR) analyses were conducted to assess the causal effect of smoking-related DNA methylation on breast cancer risk. We used 436 smoking-related CpG sites extracted from 846 middle-aged women in the ARIES project as exposure data. We collected summary data of breast cancer from one of the largest meta-analyses, including 69,501 cases for ER+ breast cancer and 21,468 cases for ER- breast cancer. A total of 485 single-nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) for smoking-related DNA methylation. We further performed an MR Steiger test to estimate the likely direction of causal estimate between DNA methylation and breast cancer. We also conducted colocalization analysis to evaluate whether smoking-related CpG sites shared a common genetic causal SNP with breast cancer in a given region. RESULTS: We established four significant associations after multiple testing correction: the CpG sites of cg2583948 [OR = 0.94, 95% CI (0.91-0.97)], cg0760265 [OR = 1.07, 95% CI (1.03-1.11)], cg0420946 [OR = 0.95, 95% CI (0.93-0.98)], and cg2037583 [OR =1.09, 95% CI (1.04-1.15)] were associated with the risk of ER+ breast cancer. All the four smoking-related CpG sites had a larger variance than that in ER+ breast cancer (all p < 1.83 × 10-11) in the MR Steiger test. Further colocalization analysis showed that there was strong evidence (based on PPH4 > 0.8) supporting a common genetic causal SNP between the CpG site of cg2583948 [with IMP3 expression (PPH4 = 0.958)] and ER+ breast cancer. There were no causal associations between smoking-related DNA methylation and ER- breast cancer. CONCLUSIONS: These findings highlight potential targets for the prevention of ER+ breast cancer. Tissue-specific epigenetic data are required to confirm these results.

Silencing TCF4 Sensitizes Melanoma Cells to Vemurafenib Through Inhibiting GLUT3-Mediated Glycolysis.

BACKGROUND: Vemurafenib is a selective BRAF inhibitor with significant early effects in melanoma, but resistance will develop with the duration of treatment. Therefore, overcoming vemurafenib resistance can effectively improve the survival rate of melanoma. The transcriptional activity of TCF4 is necessary to maintain the malignant phenotype of cancer cells. However, the effect of TCF4 on melanoma sensitivity to vemurafenib and the underlying mechanism is unclear. METHODS: Vemurafenib-resistant A375 (A375/Vem) and SK-Mel-28 (SK-Mel-28/Vem) cells were constructed by administering increasing concentrations of vemurafenib, and the expression of TCF4 was examined in parent and vemurafenib-resistant cells. TCF4 loss-function cells models were established in A375/Vem and SK-Mel-28/Vem cells, respectively. Cell survival, clone formation, and cell apoptosis were assessed. The downstream target gene of TCF4 was verified by chromatin immunoprecipitation. Finally, the effect of TCF4 on melanoma cells glycolysis was investigated and were performed. RESULTS: TCF4 expression was increased in vemurafenib-resistant melanoma cells, and knocking down TCF4 could promote the sensitivity of melanoma cells to vemurafenib. Mechanism investigation revealed that TCF4 could interact with GLUT3 and silencing TCF4 could inhibit GLUT3 expression. In addition, overexpression of GLUT3 reversed the growth and glycolysis of tumor cells that were inhibited by TCF4 knockdown. CONCLUSION: Our study demonstrates that TCF4 downregulation sensitizes melanoma cells to vemurafenib through inhibiting GLUT3-mediated glycolysis. These findings support TCF4 as an oncogene and provide new mechanism by which TCF4 confers chemotherapy resistance in melanoma.

Procalcitonin levels in COVID-19 patients.

Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a pandemic. This study analysed 95 SARS-CoV-2-infected patients, including 62 moderate COVID-19 patients, 21 severe COVID-19 patients and 12 critical COVID-19 patients (6 patients died, all critical). The results showed that the mean serum procalcitonin (PCT) levels were over four times higher in severe patients than in moderate patients and were over eight times higher in critical patients than in moderate patients. For discharged patients, both high-normal PCT levels and abnormal PCT levels decreased during recovery. However, in death cases, serum levels of PCT increased as the disease worsened. We demonstrate that PCT may be an indicator of disease severity in COVID-19 and may contribute to determining the severity of patients infected with SARS-CoV-2. Moreover, serial PCT measurements may be useful in predicting the prognosis.

Sorafenib sensitizes melanoma cells to vemurafenib through ferroptosis.

BACKGROUND: BRAF gene mutation causes melanoma patients to develop drug resistance after 8-9 months BRAF inhibitors treatment. Therefore, overcoming BRAF inhibitor resistance has important implications for improving patient survival. Sorafenib directly inhibits tumor cell proliferation by blocking the RAF/MEK/ERK-mediated cell signaling pathway. It remains unknown that whether the combination of sorafenib with vemurafenib could sensitize melanoma cells to vemurafenib, and the underlying mechanism needs to be clarified. METHODS: Vemurafenib resistant melanoma cells A375/Vem and SK-Mel-28/Vem were established by exposing to a series of concentration of vemurafenib. Cell viability was measured when A375 and SK-Mel-28 cells treated with vemurafenib or combined with sorafenib. Meanwhile the levels of Iron, GSH, MDA and reactive oxygen species (ROS) were detected. Finally we examined that whether sorafenib sensitizes melanoma cells to vemurafenib through ferroptosis. RESULTS: We found that sorafenib sensitized melanoma cells to vemurafenib. Sorafenib treatment did not significantly alter the production of ROS and the content of iron, GSH and MDA in vemurafenib resistant cells, but cotreatment of sorafenib and vemurafenib dramatically upregulated ROS production, MDA and iron, but decreased GSH concentration. Interestingly, sorafenib strongly promoted vemurafenib-induced cell death, which was blocked by lipid peroxidation inhibitors ferrostatin-1 but not ZVAD-FMK or necrosulfonamid. CONCLUSIONS: Sorafenib sensitized melanoma cells to vemurafenib by increasing ROS production through ferroptosis. Our study reveals that the combination of sorafenib may provide a novel strategy of vemurafenib resistant melanoma therapy.

Knockdown of lncRNA-UCA1 inhibits the proliferation and migration of melanoma cells through modulating the miR-28-5p/HOXB3 axis.

Long non-coding RNA urothelial carcinoma-associated 1 (UCA1) functions as an oncogene in different human cancers, including melanoma. However, the molecular mechanism of UCA1 underlying melanoma progression still remains largely unknown. In the present study, reverse transcription quantitative polymerase chain reaction and western blot analyses were used to examine the mRNA and protein expression levels, respectively. Cell Counting Kit-8 and wound healing assays were conducted to study cell proliferation and migration, respectively. A luciferase reporter assay was used to confirm the targeting relationship. It was demonstrated that UCA1 expression was increased in melanoma tissues and cell lines. In addition, UCA1 expression was higher in melanoma tissues at stage III-IV than in tissues at stage I-II. Inhibition of UCA1 expression markedly reduced melanoma cell proliferation and migration. Further investigation revealed that UCA1 functioned in melanoma cells through directly binding with microRNA (miR)-28-5p. The expression of miR-28-5p was significantly reduced in melanoma tissues and had an inverse correlation with UCA1 expression. In addition, miR-28-5p expression was higher in melanoma tissues at advanced stages than in stage I-II tissues. Furthermore, homeobox (HOX)B3 was identified as a target gene of miR-28-5p in melanoma cells, and HOXB3 overexpression reversed the suppressive effects of UCA1 downregulation on melanoma cell proliferation and migration. Finally, HOXB3 was upregulated in melanoma tissues compared with its expression in adjacent tissues, and HOXB3 expression was increased in melanoma tissues at advanced stages. Taken together, the regulatory network of the UCA1/miR-28-5p/HOXB3 axis in melanoma was demonstrated for the first time in the present study, expanding the understanding of the molecular mechanism underlying melanoma progression. Future studies may further confirm the function of this signaling pathway in vivo.