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Infection with human papillomavirus (HPV) typically leads to cervical cancer, skin related cancers and many other tumors. HPV is mainly responsible for evading immune tumor monitoring in HPV related cancers. Toll like receptors (TLRs) are particular pattern recognition molecules. When the body is facing immune danger, it can lead to innate and direct adaptive immunity. TLR plays an important role in initiating antiviral immune responses. HPV can affect the expression level of TLR and interfere with TLR related signaling pathways, resulting in sustained viral infection and even carcinogenesis. This paper introduces the HPV virus and HPV related cancers. We discussed the present comprehension of TLR, its expression and signaling, as well as its role in HPV infection. We also provided a detailed introduction to immunotherapy methods for HPV related diseases based on TLR agonists. This will provide insights into methods that support the therapeutic method of HPV related conditions with TLR agonists

Background Castleman’s disease is a rare lymphoproliferative disorder that is often misdiagnosed because of its untypical clinical or imaging features except for a painless mass. Besides, it is also difficult to cure Castleman’s disease due to its unclear pathogenesis. Case presentation We present a Castleman’s disease case with diagnostic significance regarding a 54-year-old Chinese male who has a painless mass in his left parotid gland for 18 months with a 30-years history of autoimmune disease psoriasis. Computed tomography scan showed a high-density nodule with clear boundaries in the left parotid and multiple enlarged lymph nodes in the left submandibular and neck region. General checkup, the extremely elevated serum interleukin-6 and lymph node biopsy in the left submandibular region gave us an initial suspicion of Castleman’s disease. Then the patient underwent a left superficial parotidectomy. Based on histopathologic analysis, we made a certain diagnosis of Castleman’s disease and gave corresponding treatments. In 18 months of follow-up, the patient showed no evidence of recurrence, with the level of serum interleukin-6 decreased. Conclusions Clinicians should be aware of the possibility of Castleman’s disease when faced with masses or enlarged lymph nodes in the parotid gland to avoid misdiagnosis, especially in patients with autoimmune diseases and elevated serum interleukin-6.

The exploration of artificial metal-peptide assemblies (MPAs) is one of the most exciting fields because of their great potential for simulating the dynamics and functionality of natural proteins. However, unfavorable enthalpy changes make forming discrete complexes with large and adaptable cavities from flexible peptide ligands challenging. Here, we present a strategy integrating metal-cluster building blocks and peptides to create chiral metal-peptide assemblies and get a family of enantiopure [ R-/S- Ni 3 L 2 ] n (n = 2, 3, 6) MPAs, including the R-/S- Ni 6 L 4 capsule, the S- Ni 9 L 6 trigonal prism, and the R-/S- Ni 18 L 12 octahedron cage. X-ray crystallography shows MPA formation reactions are highly solvent-condition-dependent, resulting in significant changes in ligand conformation and discrete cavity sizes. Moreover, we demonstrate that a structure transformation from Ni 18 L 12 to Ni 9 L 6 in the presence of benzopyrone molecules depends on the peptide conformational selection in crystallization. This work reveals that a metal-cluster building block approach enables facile bottom-up construction of artificial metal-peptide assemblies. The use of metal clusters to construct artificial protein-mimic structures with adaptable cavities has potential for simulating the dynamics and functionality of natural proteins. Here, the authors develop a family of chiral metal-peptide assemblies using {Ni3} clusters and flexible peptides, resulting in structures such as octahedral cages, trigonal prisms, and capsules.

Vitrification reduces the fertilisation capacity and developmental ability of mammalian oocytes; this effect is closely associated with an abnormal increase of cytoplasmic free calcium ions ([Ca 2+ ]i). However, little information about the mechanism by which vitrification increases [Ca 2+ ]i levels or a procedure to regulate [Ca 2+ ]i levels in these oocytes is available. Vitrified bovine oocytes were used to analyse the effect of vitrification on [Ca 2+ ]i, endoplasmic reticulum Ca 2+ (ER Ca 2+ ), and mitochondrial Ca 2+ (mCa 2+ ) levels. Our results showed that vitrification, especially with dimethyl sulfoxide (DMSO), can induce ER Ca 2+ release into the cytoplasm, consequently increasing the [Ca 2+ ]i and mCa 2+ levels. Supplementing the cells with 10 μM 1,2-bis (o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA-AM or BAPTA) significantly decreased the [Ca 2+ ]i level and maintained the normal distribution of cortical granules in the vitrified bovine oocytes, increasing their fertilisation ability and cleavage rate after in vitro fertilisation (IVF). Treating vitrified bovine oocytes with 1 μM ruthenium red (RR) significantly inhibited the Ca 2+ flux from the cytoplasm into mitochondria; maintained normal mCa 2+ levels, mitochondrial membrane potential, and ATP content; and inhibited apoptosis. Treating vitrified oocytes with a combination of BAPTA and RR significantly improved embryo development and quality after IVF.

To manufacture dental restorations composed of lithium disilicate (LD) through the computer-aided design and manufacturing (CAD/CAM) process, thermal refinement is an essential process that can affect the optical and mechanical properties of ceramics. In this study, we aimed to evaluate the translucency and flexural strength of lithium disilicate glass–ceramic for CAD/CAM using different thermal refinement schedules and thicknesses by measuring the total transmission of light through the specimen and calculating the peak load of the specimen until fracture in a piston-on-three-ball test, respectively. The results showed that a lower translucency was exhibited in thicker specimens, and the flexural strength decreased in the order of 1.0, 0.5, and 2.0 mm (p < 0.05). The lithium disilicates thermally refined at a heat of 820 degrees were shown to have the highest biaxial flexural strength (p < 0.05). These findings suggest that it is possible to adjust transparency and strength according to the clinical situation by choosing an appropriate thickness and thermal refinement process.

Our previous research has shown that galanin plays an antinociceptive effect via binding to galanin receptors (GalRs) in nucleus accumbens (NAc). This study focused on the involvement of GalR2 in galanin-induced antinociceptive effect in NAc of neuropathic pain rats. The chronic constriction injury of sciatic nerve (CCI) was used to mimic neuropathic pain model. The hind paw withdrawal latency (HWL) to thermal stimulation and hind paw withdrawal threshold (HWT) to mechanical stimulation were measured as the indicators of pain threshold. The results showed that 14 and 28 days after CCI, the expression of GalR2 was up-regulated in bilateral NAc of rats, and intra-NAc injection of GalR2 antagonist M871 reversed galanin-induced increases in HWL and HWT of CCI rats. Furthermore, intra-NAc injection of GalR2 agonist M1145 induced increases in HWL and HWT at day 14 and day 28 after CCI, which could also be reversed by M871. Finally, we found that M1145-induced antinociceptive effect in NAc of CCI rats was stronger than that in intact rats. These results imply that the GalR2 is activated in the NAc from day 14 to day 28 after CCI and GalR2 is involved in the galanin-induced antinociceptive effect in NAc of CCI rats.

Little information is available regarding the effect of melatonin on the quality and fertilization capability of sex-sorted bull sperm, and even less about the associated mechanism. Sex-sorted sperm from three individual bulls were washed twice in wash medium and incubated in a fertilization medium for 1.5 h, and each was supplemented with melatonin (0, 10−3 M, 10−5 M, 10−7 M, and 10−9 M). The reactive oxygen species (ROS) and endogenous antioxidant activity (glutathione peroxidase (GPx); superoxide dismutase (SOD); catalase (CAT)), apoptosis (phosphatidylserine [PS] externalization; mitochondrial membrane potential (Δψm)), acrosomal integrity events (malondialdehyde (MDA) level; acrosomal integrity), capacitation (calcium ion [Ca2+]i level; cyclic adenosine monophosphate (cAMP); capacitation level), and fertilization ability of the sperm were assessed. Melatonin receptor 1 (MT1) and 2 (MT2) expression were examined to investigate the involvement of melatonin receptors on sex-sorted bull sperm capacitation. Our results show that treatment with 10−5 M melatonin significantly decreased the ROS level and increased the GPx, SOD, and CAT activities of sex-sorted bull sperm, which inhibited PS externalization and MDA levels, and improved Δψm, acrosomal integrity, and fertilization ability. Further experiments showed that melatonin regulates sperm capacitation via MT1. These findings contribute to improving the fertilization capacity of sex-sorted bull sperm and exploring the associated mechanism.

Jasmonic acid (JA) plays an important role in regulating leaf senescence. However, the molecular mechanisms of leaf senescence in apple (Malus domestica) remain elusive. In this study, we found that MdZAT10, a C2H2-type zinc finger transcription factor (TF) in apple, markedly accelerates leaf senescence and increases the expression of senescence-related genes. To explore how MdZAT10 promotes leaf senescence, we carried out liquid chromatography/mass spectrometry screening. We found that MdABI5 physically interacts with MdZAT10. MdABI5, an important positive regulator of leaf senescence, significantly accelerated leaf senescence in apple. MdZAT10 was found to enhance the transcriptional activity of MdABI5 for MdNYC1 and MdNYE1, thus accelerating leaf senescence. In addition, we found that MdZAT10 expression was induced by methyl jasmonate (MeJA), which accelerated JA-induced leaf senescence. We also found that the JA-responsive protein MdBT2 directly interacts with MdZAT10 and reduces its protein stability through ubiquitination and degradation, thereby delaying MdZAT10-mediated leaf senescence. Taken together, our results provide new insight into the mechanisms by which MdZAT10 positively regulates JA-induced leaf senescence in apple.

Acute ischemic stroke (AIS) is a leading cause of mortality and disability worldwide. Intravenous thrombolysis (IVT) improves recovery, but predicting outcomes remains challenging. Machine learning (ML) and biomarkers like ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein β (S100β), and neuron-specific enolase (NSE) may enhance prognostic accuracy. We aimed to assess the predictive value of serum brain injury biomarkers for 3-month outcomes in AIS patients treated with IVT, using an ML-based model. A multicenter prospective cohort study was conducted, enrolling AIS patients treated with recombinant tissue plasminogen activator from 16 hospitals. Of 1580 patients, 1028 were included and divided into training (  = 571), testing (  = 243), and external validation (  = 214) cohorts. Thirty-three variables, including demographics, clinical data, and biomarkers (UCH-L1, S100β, NSE), were analyzed. Least Absolute Shrinkage and Selection Operator regression was used for feature selection, and six ML algorithms were tested. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), 1-score, calibration curve, and decision curve analysis. The light gradient boosting machines (LightGBM) model achieved the best performance in the training dataset (AUC: 0.846; 1-score: 0.789) and external validation dataset (AUC: 0.714). Eight critical predictors, including age, admission National Institutes of Health Stroke Scale (NIHSS) score, Trial of Org 10172 in Acute Stroke Treatment, white blood cell, finger blood glucose, UCH-L1, S100β, and NSE, were identified and incorporated into an ML model for clinical application. Shapley additive interpretation analysis enhances the interpretability of the model, with NIHSS score and NSE as top contributors. External validation confirmed good calibration and consistent net benefit across threshold probabilities (0.1-0.8). Integrating serum biomarkers (UCH-L1, S100β, NSE) with ML significantly improves 3-month outcome prediction in AIS patients. The LightGBM model offers robust performance and clinical interpretability for individualized treatment planning.

The aim of this study was to test the effects of five different concentrations (0, 10 −3 , 10 −4 , 10 −5 , and 10 −6  M) of resveratrol (Res) supplementation in bull sperm washing and fertilisation medium on levels of reactive oxygen species (ROS), phosphatidylserine (PS) externalisation, mitochondrial membrane potential (Δψm), ATP and malondialdehyde (MDA), acrosomal integrity, blastocyst rate, and blastocyst quality after in vitro fertilisation (IVF). The results for sex-sorted sperm from three bulls showed: (1) ROS and MDA levels in 10 −3  M and 10 −4  M Res groups were significantly lower than those of controls ( P  < 0.05); (2) the percentage of viable sperm, percentage of sperm with high Δψm, and the ATP content in 10 −3  M and 10 −4  M Res groups were significantly higher than those of controls ( P  < 0.05); (3) the percentage of viable sperm with acrosomal integrity, and the blastocyst percentage and quality of the 10 −4  M Res group were significantly higher than those of controls ( P  < 0.05). In conclusion, 10 −4  M Res supplementation in washing and fertilisation medium of sex-sorted bull sperm significantly decreased ROS, PS externalisation, and MDA, and protected mitochondrial function and acrosomal integrity, thereby increasing blastocyst percentage and quality following IVF.