High temperature and humidity in the environment disrupt bile acid metabolism, the gut microbiome, and GLP-1 secretion in mice.

High temperature and humidity in the environment are known to be associated with discomfort and disease, yet the underlying mechanisms remain unclear. We observed a decrease in plasma glucagon-like peptide-1 levels in response to high-temperature and humidity conditions. Through 16S rRNA gene sequencing, alterations in the gut microbiota composition were identified following exposure to high temperature and humidity conditions. Notably, changes in the gut microbiota have been implicated in bile acid synthesis. Further analysis revealed a decrease in lithocholic acid levels in high-temperature and humidity conditions. Subsequent in vitro experiments demonstrated that lithocholic acid increases glucagon-like peptide-1 secretion in NCI-H716 cells. Proteomic analysis indicated upregulation of farnesoid X receptor expression in the ileum. In vitro experiments revealed that the combination of lithocholic acid with farnesoid X receptor inhibitors resulted in a significant increase in GLP-1 levels compared to lithocholic acid alone. In this study, we elucidate the mechanism by which reduced lithocholic acid suppresses glucagon-like peptide 1 via farnesoid X receptor activation under high-temperature and humidity condition.

Local Confinement Effects of Block Copolymers Driving Self-Assembly of Nanoparticles into Discrete Pancake-Shaped Superlattices.

The utilization of polymer conformations to construct a variety of superlattices is a common method within the field. However, this technique often results in only long-range ordering rather than the formation of distinct superlattices. In this study, a well-organized array of discrete pancake-shaped superlattices (DPSs) is successfully obtained through the utilization of air-liquid interface self-assembly, facilitated by the confined environment created by a block copolymer. It is crucial to note that both the self-assembly behavior and resulting morphologies of the DPSs can be precisely tuned by adjusting several experimental parameters, most notably the concentration and molecular architecture of the block copolymers. Furthermore, this work provides valuable insights into the formation processes and mechanisms underpinning the DPSs. The approach described here is both straightforward and efficacious, establishing a strong foundation for subsequent research and the development of non-close-packed superlattice structures.

Nanocomposites of Conducting Polymers and 2D Materials for Flexible Supercapacitors.

Flexible supercapacitors (FSCs) with high electrochemical and mechanical performance are inevitably necessary for the fabrication of integrated wearable systems. Conducting polymers with intrinsic conductivity and flexibility are ideal active materials for FSCs. However, they suffer from poor cycling stability due to huge volume variations during operation cycles. Two-dimensional (2D) materials play a critical role in FSCs, but restacking and aggregation limit their practical application. Nanocomposites of conducting polymers and 2D materials can mitigate the above-mentioned drawbacks. This review presents the recent progress of those nanocomposites for FSCs. It aims to provide insights into the assembling strategies of the macroscopic structures of those nanocomposites, such as 1D fibers, 2D films, and 3D aerogels/hydrogels, as well as the fabrication methods to convert these macroscopic structures to FSCs with different device configurations. The practical applications of FSCs based on those nanocomposites in integrated self-powered sensing systems and future perspectives are also discussed.

Molten-Salt-Assisted Strategy Enables High-Rate Micron-Sized Single-Crystal Li-Rich, Mn-Based Layered Oxide Cathode Materials.

Li-rich Mn-based layered oxides (LMLOs) are expected to be the most promising high-capacity cathodes for the next generation of lithium-ion batteries (LIBs). However, the poor cycling stability and kinetics performance of polycrystalline LMLOs restrict their practical applications due to the anisotropic lattice stress and crack propagation during cycling. Herein, B-doped micron-sized single-crystal Co-free LMLOs were obtained by molten-salt (LiNO3 and H3BO3)-assisted sintering. The results reveal that the low-melting-point molten salt can serve as liquid-phase media to improve the efficiency of atomic mass transfer and crystal nucleation and growth. The modified single-crystal LMLO cathodes can resist the accumulation of anisotropic stress and strain during the cycling and reduce interface side reactions, thus achieving excellent high-voltage stability and kinetics performance. The reversible specific capacity of the single crystals is 210.8 mAh g-1 at 1C with a voltage decay rate of 1.95 mV/cycle and up to 161.1 mAh g-1 at 10C with a capacity retention of 81.06% after 200 cycles.

Efficient conversion of cane molasses into Tremella fuciformis polysaccharides with enhanced bioactivity through repeated batch culture.

Tremella fuciformis polysaccharide (TFPS) is a natural mushroom mucopolysaccharide widely used in health foods, medical care, cosmetic and surgical materials. In this study, we developed an efficient strategy for the repeated batch production of highly bioactive TFPS from the agro-industrial residue cane molasses. Cane molasses contained 39.92 % sucrose (w/w), 6.36 % fructose and 3.53 % glucose, all of which could be utilized by T. fuciformis spores, whereas, the TFPS production efficiency only reached 0.74 g/L/d. Corn cobs proved to be the best immobilized carrier that could tightly absorb spores and significantly shorten the fermentation lag period. The average yield of TFPS in eight repeated batch culture was 5.52 g/L with a production efficiency of 2.04 g/L/d. The average fermentation cycle after optimization was reduced by 61.61 % compared with the initial conditions. Compared to glucose as a carbon source, cane molasses significantly increased the proportion of low-molecular-weight TFPS (TFPS-2) in total polysaccharides from 3.54 % to 17.25 % (w/w). Moreover, TFPS-2 exhibited potent antioxidant capacity against four free radicals (O2-, ABTS+, OH, and DPPH). In conclusion, this study lays the foundation for the efficient conversion of cane molasses and production of TFPS with high bioactivity.

Medical errors, affected sites, and adverse consequences among patients in the orthopaedic department: Does age matter?

Background: Orthopaedics have become the focus of research on patient safety due to the high incidence of medical errors. Previous studies were based on all orthopaedic patients and rarely conducted empirical analyses from the perspective of age. This study aimed to fill the academic gap in the age variable by comparing medical errors, affected sites, and adverse consequences in orthopaedic patients. Methods: This retrospective study included 329 litigation claims against orthopaedists using data from China Judgments Online. First, we performed computer crawling and screened 5,237 litigation documents using keywords, including medical errors. Second, 2,536 samples were retained through systematic random sampling, and 549 irrelevant cases were deleted after manual reading. Finally, three clinicians from different medical departments selected 329 incidents related to orthopaedics for further analysis, according to the description of the lawsuits. Three other professional orthopaedists evaluated the patients' ages, affected sites of medical errors, and adverse consequences. Results: The greatest number of medical errors was observed in the joints (30.43%) for all orthopaedic patients. However, adult patients (aged 18-60 years) were most susceptible to errors in the extremities (30.42%). A higher rate of complications was associated with a higher rate of morbidity/mortality for the corresponding patients. Medical errors correlated with complications occurred in the following sites: joints (15.38%), extremities (12.50%), spine (16.95%), multiple sites (15.38%), and hands and feet (14.81%). In addition to surgical errors, over 10% of all orthopaedic patients experienced missed diagnoses. The incidence of insufficient adherence to informed consent obligations was 13.5% among adult patients and was much higher in paediatric and older adults patients. When orthopaedic patients suffered from medical technical errors, iatrogenic mortality/morbidity would decrease by 0.3% for one unit increase in age. Conclusion: Dividing patients into different ages demonstrated diverse results in terms of medical errors and affected sites. Negligence in diagnosis and examination can be fatal factors that endanger safety, and complications may cause morbidity/mortality. When patients suffered from technical errors, age is inversely proportional to mortality/morbidity. Special attention needs to be paid to technical errors in the younger older adults population (60-64 years old), which has inspired implications in promoting aging and public health.

Effect of dexmedetomidine on postoperative nausea and vomiting in female patients undergoing radical thoracoscopic lung cancer resection.

Introduction: Postoperative nausea and vomiting (PONV) is a prevalent postsurgical complication. The objective of our study was to compare the effect of different doses of dexmedetomidine on PONV in female patients undergoing radical thoracoscopic lung cancer resection. Methods: A total of 164 female patients undergoing elective thoracoscopic radical lung cancer surgery were enrolled and assigned to one of four groups. Patients received 0.2 µg/kg/h, 0.4 µg/kg/h, 0.8 µg/kg/h dexmedetomidine and normal saline in the Dex1, Dex2, Dex3 and Control groups, respectively. The primary outcome was the incidence of PONV during 48 h postoperatively. The second outcomes included the incidence of PONV and postoperative vomiting (POV) at four time points postoperatively (T1: PACU retention period; T2: PACU discharge to postoperative 12 h; T3: postoperative 12 h-postoperative 24 h; T4: postoperative 24 h-postoperative 48 h), the area under the curve of PONV grade (PONVAUC), PONV grade, POV grade and other postoperative recovery indicators. Results: The incidence of PONV differed among the four groups. The Dex2 group (29.27%) was lower than that in the Dex1 group (61.90%) and Control group (72.50%). The incidence of PONV at T2 in the Dex1 group (11.90%) and Dex2 group (9.76%) was lower than that in the Control group (42.50%). The incidence of PONV at T3 in the Dex2 group (29.27%) was lower than that in the Dex1 group (61.90%) and Control group (62.50%). The PONVAUC was lower in the Dex2 group than in the Control group. The incidence of POV at T3 in the Dex2 and Dex3 groups was lower than that in the Control group. The consumption of remifentanil, norepinephrine, PACU dwell time, VAS scores, postoperative PCA press frequency, and the time for the first postoperative oral intake were different among the four groups. The regression model shows that the Dex2 group is a protective factor for PONV. Conclusion: Dexmedetomidine can reduce the incidence of PONV and accelerate postoperative recovery in female patients undergoing radical thoracoscopic lung cancer resection. Compared with the other two dosages, 0.4 µg/kg/h dexmedetomidine is preferable. Clinical Trial Registration: chictr.org.cn, identifier ChiCTR2300071831.

IMoVR-Net: A robust interpretable network for multi-ocular lesion recognition from TAO facial images.

Thyroid-associated ophthalmopathy (TAO) is an organ-specific autoimmune disease that seriously affects patient's life and health. However, the early diagnosis of TAO is highly dependent on the physician's subjective experience. Moreover, the currently proposed deep learning networks for eye diseases do not provide robust interpretability concerning feature learning paradigm, model structure, and the number of neurons. But the mentioned components are very important for model interpretability and are key factors that severely affect the transparency of the model. Therefore, a robust interpretable multi-orientation visual recognition network (IMoVR-Net) for TAO multi-ocular lesion recognition is proposed in this paper. Firstly, a multi-orientation visual cascaded encoder composed of the DenseGabor module and the dilated Gabor convolution group is proposed to achieve the fine extraction of multi-directional TAO lesion features by using a novel feature learning paradigm called alternating filtering. Besides, combining information theory and topology tool, an optimization rule based on topological energy entropy is proposed to provide a solid interpretable theory for determining the model structure. Finally, a clustering correlation analysis method is developed to accomplish the determination of the number of convolutional hidden neurons, providing robust interpretability for the selection of the number of neurons. Compared to other advanced models, the IMoVR-Net achieved state-of-the-art performance on different TAO ocular datasets with an average accuracy, sensitivity, precision, and F1 score of 0.878, 87.27 %, 0.875, and 87.39 %, respectively. The IMoVR-Net has good clinical application prospects due to its strong recognition ability and robust interpretability in feature extraction paradigm, model structure, and number of convolutional neurons.

Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice.

CONTEXT: Aryl hydrocarbon receptor (AhR) agonists are potential therapeutic agents for ulcerative colitis (UC). Indirubin (IDR), which is a natural AhR ligand approved for leukemia treatment, ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the therapeutic mechanisms of IDR are unknown, limiting its application. OBJECTIVE: This study explores the therapeutic mechanisms of IDR in DSS-induced colitis using transcriptomic analysis. MATERIALS AND METHODS: Male BALB/c mice were categorized to six groups: normal, DSS model (2% DSS), IDR treatment (10, 20 and 40 mg/kg), and sulfasalazine (520 mg/kg) groups. The drugs were intragastrically administered for 7 consecutive days. The disease activity index (DAI) was recorded. After euthanasia, the colon length was measured, and histopathological examination, immunohistochemistry staining using F4/80, and colonic transcriptomic analysis were conducted. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB) were conducted to verify our findings. RESULTS: Compared with DSS, IDR treatment decreased the DAI score by 64.9% and increased colon length by 26.2%. Moreover, it alleviated mucosal injury and reduced macrophage infiltration. Transcriptomic analysis identified several downregulated genes (Igkvs and Nlrp3), as well as Nlrp3/Il1ß and hemoglobin gene networks, after IDR treatment. The abundances of NF-κB p65, NLRP3, IL-1ß, and HBA decreased by 69.1, 59.4, 81.1, and 83.0% respectively, after IDR treatment. DISCUSSION AND CONCLUSION: Apart from the well-documented NF-κB signalling pathway, IL-17A, and NLRP3-IL-1ß, the suppression of haemoglobin-induced lipid peroxidation could be a previously unknown mechanism of IDR. Our study can help improve its application for UC treatment.

Sex and age differences in chronic postoperative pain among patients undergoing thoracic surgery: a retrospective cohort study.

Background: The effect of sex and age on chronic post-thoracic surgical pain (CPTP) at rest and with activity remains unclear. The main purpose of this study was to investigate the relationship between the incidence of chronic postoperative pain (at rest and with activity) and sex/age differences. Methods: This was a single-center retrospective study that included adult patients who had undergone elective thoracic surgery. Patients were divided into two groups based on sex. Demographic and perioperative data were collected, including age, sex, education level, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) physical status, and medical history (hypertension, diabetes mellitus). Chronic postoperative pain data were collected by telephone follow-up. Results: Among the 3,159 patients enrolled, 1,762 were male, and 1,397 were female. After creating a matched-pairs cohort, 1,856 patients were analyzed. The incidence of CPTP at rest was 14.9% among males and 17.8% among females (p = 0.090). The incidence of CPTP with activity was 28.4% among males and 35.0% among females (p = 0.002). We analyzed three different models after propensity matching to validate the stability of the prediction model between sex and CPTP, and female sex was a significant predictor of CPTP with activity 3 months after surgery. Further analysis showed that females in the 45-55-year-old age group were more prone to develop CPTP. Conclusion: Females have a higher incidence of chronic postoperative pain with activity after thoracic surgery. Females in the 45-55-year-old age group are more prone to develop CPTP than females in other age groups.

Effects of preoperative current smoking on chronic postsurgical pain in thoracic surgery: a retrospective cohort study.

OBJECTIVE: This study aimed to investigate the effect of preoperative current smoking on chronic postsurgical pain in patients who underwent thoracic surgery. METHODS: A total of 5,395 patients aged over 18 years old who underwent thoracic surgery from January 2016 to March 2020 in Henan Provincial People's Hospital were enrolled. Patients were divided into two groups: the smoking group (SG group) and the nonsmoking group (NSG group). Propensity score matching was utilized to eliminate the influence of confounding factors, and a multivariable logistic regression model was established to determine the effect of preoperative current smoking on chronic postsurgical pain. The dose-response relationship between the smoking index (SI) and chronic postsurgical pain at rest was analyzed using a restricted cubic spline curve. RESULTS: In a matched cohort of 1028 patients, the incidence of chronic pain at rest was 13.2% in the smoking group and 19.0% in the nonsmoking group (P = 0.011). Three different models were used to verify the stability of the model between preoperative current smoking and chronic postsurgical pain. A regression model was established to determine the influence of different smoking indexes (SIs) on chronic postsurgical pain. The incidence of chronic pain at rest was lower in patients with SI ≥400 before thoracic surgery than in patients whose SI was less than 400. CONCLUSIONS: A relationship between the preoperative current smoking index and chronic postsurgical pain at rest was observed. The incidence of chronic postsurgical pain at rest was lower in patients whose SI was greater than 400.

A High-Relative-Bandwidth Doherty Power Amplifier with Modified Load Modulation Network for Wireless Communications.

This paper presents a novel load modulation network to realize a broadband Doherty power amplifier (DPA). The proposed load modulation network consists of two generalized transmission lines and a modified coupler. A comprehensive theoretical analysis is carried out to explain the operation principles of the proposed DPA. The analysis of the normalized frequency bandwidth characteristic shows that a theoretical relative bandwidth of approximately 86% can be obtained across a normalized frequency range of 0.4-1.0. The complete design process that allows the design of the large-relative-bandwidth DPA based on derived parameter solutions is presented. A broadband DPA operating between 1.0 GHz and 2.5 GHz was fabricated for validation. Measurements demonstrate that the DPA can deliver an output power of 43.9-44.5 dBm with a drain efficiency of 63.7-71.6% in the 1.0-2.5 GHz frequency band at the saturation level. Moreover, a drain efficiency of 45.2-53.7% can be obtained at the 6 dB power back-off level.

Rapidly and ultra-sensitive colorimetric detection of H2O2 and glucose based on ferrous-metal organic framework with enhanced peroxidase-mimicking activity.

In this article, a novel metal-organic framework, namely MIL-101(FeII), was firstly synthesized via a facile method. In the presence of H2O2, MIL-101(FeII) possesses excellent peroxidase-like activity toward the classical chromogenic substrate, N,N-Diethyl-p-phenylenediamine sulfate salt (DPD). The substitution of Fe2+ enhances the construction of Fe(II)-oxo nodes and accelerates electrons transfer between DPD and H2O2, thereby improving the peroxidase-mimicking catalytic activity of MIL-101(FeII) nanoenzyme. Additionally, DPD molecules could be adsorbed readily onto the surface of the nanoparticles due to the π-π interaction. The study of Michaelis constant indicates that the MIL-101(FeII) exhibits a higher affinity towards DPD (0.16 mM) in contrast to horseradish peroxidase (0.78 mM). In view of the impressive catalytic performance of MIL-101(FeII), two reliable monitoring platforms for the rapid detection of H2O2 and glucose were established with extremely low detection limits of 18.04 nM and 0.87 µM in the ranges of 40-5000 nM and 1.2-300 µM, respectively. The study of the catalytic mechanism indicates that DPD oxidation is attributed to the hydroxyl radical (·OH) produced from the decomposition of H2O2 catalyzed by MIL-101(FeII). Furthermore, the developed sensor indicates high selectivity and stability and can be effectively appropriate for the detection of H2O2 and glucose in real samples. This work not only provides a novel nanozyme with superior catalytic performance for biological analysis, but also broadens the application field of MIL-101(FeII) material.

Case Report: From epilepsy and uterus didelphys to Turner syndrome-associated dysgerminoma.

Dysgerminoma is a rare occurrence in Turner syndrome patients without Y chromosome mosaicism or hormone therapy during puberty. We present a unique case of a 33-year-old nulliparous Chinese woman with intermittent epilepsy and Mullerian anomalies carrying a double uterus, cervix, and vagina. The patient is also characterized as having Turner syndrome accompanied by 46,X, del(Xp22.33-11.23) and del(2)(q11.1-11.2). MRI exhibited a 17.0 cm × 20.0 cm × 10.5 cm solid ovarian lesion. Radical surgery and pathology revealed dysgerminoma at stage IIIc with lymphatic metastases and a KIT gene mutation identified in exon 13. Furthermore, the tumor microenvironment (TME) displayed robust expression of CD4+ T lymphocytes and PD-1, whereas the distribution of CD8+ T lymphocytes and PDL-1 was sporadic. Despite the administration of enoxaparin to prevent thromboembolism, the patient experienced multiple cerebral infarctions during chemotherapy. Subsequently, the patient chose to decline further treatment and was discharged. This exceptional case imparts several noteworthy lessons. First, the coexistence of Mullerian anomalies, although rare, is not incompatible with Turner syndrome. Second, screening for KIT mutations is imperative to reduce the risk of dysgerminoma in Turner syndrome, especially for patients with Y mosaicism who are recommended for hormone replacement therapy. Lastly, comprehensive anticoagulation therapy is crucial for Turner syndrome patients undergoing cisplatin-based chemotherapy.

Effect of landscape design on depth perception in classical Chinese gardens: A quantitative analysis using virtual reality simulation.

It is common for visitors to have rich and varied experiences in the limited space of a classical Chinese garden. This leads to the sense that the garden's scale is much larger than it really is. A main reason for this perceptual bias is the gardener's manipulation of visual information. Most studies have discussed this phenomenon in terms of qualitative description with fragmented perspectives taken from static points, without considering ambient visual information or continuously changing observation points. A general question arises, then, on why depth perception can vary from one observation point to another along a garden path. To better understand the spatial experience in classical Chinese gardens, this study focused on variations in perceived depth among different observation points and aimed to identify influential visual information through psychophysical experimentation. As stimuli for the experiment, panoramic photos of Liu garden were taken from three positions at Lvyin Pavilion. Considering the effects of pictorial visual cues on depth perception, the photos were processed to create 18 kinds of stimuli (six image treatments * three positions). Two tasks were presented to the participants. In Task 1, 71 participants were asked to rate the depth value of the garden using the magnitude estimation method in a cave automatic virtual environment (CAVE). Statistical analysis of Task 1 revealed that depth values differed significantly among different viewpoints. In Task 2, participants were asked to compare 18 stimuli and 3D images presented on three connected monitors and to judge the depth of the garden using the adjustment method. The results of Task 2 again showed that depth values differed significantly among different viewpoints. In both tasks, ambient information (i.e., the perspective of interior space) significantly influenced depth perception.

Shubnikov-de Haas oscillations and nontrivial topological states in Weyl semimetal candidate SmAlSi.

The RAlX (R = Light rare earth; X = Ge, Si) compounds, as a family of magnetic Weyl semimetal, have recently attracted growing attention due to the tunability of Weyl nodes and its interactions with diverse magnetism by rare-earth atoms. Here, we report the magnetotransport evidence and electronic structure calculations on nontrivial band topology of SmAlSi, a new member of this family. At low temperatures, SmAlSi exhibits large non-saturated magnetoresistance (MR) (as large as ∼5500% at 2 K and 48 T) and distinct Shubnikov-de Haas (SdH) oscillations. The field dependent MRs at 2 K deviate from the semiclassical (µ0H)2variation but follow the power-law relation MR∝(µ0H)mwith a crossover fromm∼ 1.52 at low fields (µ0H< 15 T) tom∼ 1 under high fields (µ0H> 18 T), which is attributed to the existence of Weyl points and electron-hole compensated characteristics with high mobility. From the analysis of SdH oscillations, two fundamental frequencies originating from the Fermi surface pockets with non-trivialπBerry phases and small cyclotron mass can be identified, this feature is supported by the calculated electronic band structures with two Weyl pockets near the Fermi level. Our study establishes SmAlSi as a paradigm for researching the novel topological states of RAlX family.

The current-voltage measurements under flat-top pulsed magnetic fields for non-ohmic transport study.

Investigation of the non-ohmic transport behaviors under high magnetic fields can provide a new way to explore novel field-induced phenomena. We present the current-voltage measurements under high magnetic fields based on the flat-top pulsed magnetic field system. Two different measurement strategies were compared, given that the excitation current swept continuously or increased by a series of pulses. For the short duration of the flat-top pulsed field, the continuous current method was adopted and well optimized to reduce the Joule heating and achieve the quasi-static measurements. Finally, the non-ohmic behaviors of a quasi-one-dimensional charge density wave Li0.9Mo6O17 were successfully studied under the magnetic field up to 30 T at 4.2 K, which was the first current-voltage measurements carried out in pulsed magnetic fields.

Effects of hsa-miR-28-5p on Adriamycin Sensitivity in Diffuse Large B-Cell Lymphoma.

Background: Adriamycin (doxorubicin) is an important traditional drug that exhibits cytotoxicity in Diffuse Large B-cell Lymphoma (DLBCL). Doxorubicin affects the DLBCL cells at all stages of their cell cycle. Combined with our previous results, this study discovered that the overexpression of hsa-miR-28-5p inhibited the proliferation, promoted apoptosis, and triggered cell cycle arrest at the S-phase in DLBCL cells. However, the effect of (Homo sapiens, hsa)-microRNA (miR)-28-5p on doxorubicin sensitivity in DLBCL has not been investigated. This study aims to reveal the effects of hsa-miR-28-5p on doxorubicin sensitivity at the level of DLBCL cells. Methods: To determine the optimal concentration of doxorubicin, different concentrations of doxorubicin were used to treat DLBCL cells. CCK-8 assay was used to detect the proliferation of DLBCL cells. The hsa-miR-28-5p-mimic NC and hsa-miR-28-5p mimic were transfected to doxorubicin-mediated DLBCL cells. Simultaneously, blank control groups were set up. The cells were cultured and transfected for 24 h. Next, each group was administered with different concentrations of doxorubicin and cultured again for 24 h to observe the effects of hsa-miR-28-5p on doxorubicin sensitivity at different times. The proliferation, early apoptosis, and late apoptosis in DLBCL cells were determined using soft agar colony-forming assay, mitochondrial membrane potential assay, and caspase-3 activity assay, respectively. The apoptosis and cell cycle were explored using Annexin V-PE/7-AAD and PI/RNase staining buffer, respectively. We speculated that PD-L1 might be involved in the effect of hsa-miR-28-5p on the sensitivity of adriamycin (doxorubicin) in the DLBCL cells. Hence, we performed immunohistochemistry (IHC) to determine PD-L1 expression within formalin-fixed paraffin-embedded (FFPE) samples from 52 DLBCL cases. Results: The optimal concentration of doxorubicin targeting DLBCL cells was found to be 3.028 µmol/l. The effect of doxorubicin on DLBCL cells was time- and concentration-dependent. hsa-miR-28-5p mimic + doxorubicin remarkably decreased proliferation of DLBCL. DLBCL cell apoptosis rate was the highest in hsa-miR-28-5p mimic + doxorubicin group. Apart from that, hsa-miR-28-5p mimic plus doxorubicin had the best effect in promoting DLBCL cell apoptosis. After the intervention of hsa-miR-28-5p mimic + doxorubicin on DLBCL cells, the cell cycle was arrested in the S-phase and DNA synthesis was blocked. hsa-miR-28-5p mimic + doxorubicin could regulate the cycle of DLBCL cells. As a result, overexpression of hsa-miR-28-5p combined with doxorubicin is possibly involved in the development of DLBCL by affecting the proliferation, apoptosis, and cycle of DLBCL cells. PD-L1 showed an association with the prognosis of DLBCL patients. Combining with the literature, this suggested hsa-miR-28-5p may influence DLBCL occurrence and therapeutic effect by regulating the PD-L1 level. Conclusion: The combination of hsa-miR-28-5p mimic and doxorubicin may be considered more effective in inhibiting growth, arresting the cell cycle, and promoting cell apoptosis of DLBCL cells compared to using doxorubicin alone. The effects of doxorubicin on DLBCL cells were found to be time- and concentration-dependent. The overexpression of hsa-miR-28-5p enhanced the effect of doxorubicin on DLBCL cells, which may be attributed to the regulation of PD-L1 levels.

A Novel Prognostic Signature Associated With the Tumor Microenvironment in Kidney Renal Clear Cell Carcinoma.

Background: The tumor microenvironment (TME) is a complex and evolving environment, and the tumor immune microenvironment in kidney renal clear cell carcinoma (KIRC) has a strong suppressive profile. This study investigates the potential prognostic role and value of genes of the tumor microenvironment in KIRC. Methods: The transcriptome sequencing data of 530 cases and 39 cases of KIRC and the corresponding clinical prognosis information were downloaded from TCGA data and GEO data, respectively, and TME-related gene expression profiles were extracted. A prognostic signature was constructed and evaluated using univariate Cox regression analysis and LASSO regression analysis. Gene set enrichment analysis (GSEA) was used to obtain the biological process of gene enrichment in patients with high and low-risk groups. Results: A prognostic signature consisting of eight TME-related genes (LRFN1, CSF1, UCN, TUBB2B, SERPINF1, ADAM8, ABCB4, CCL22) was constructed. Kaplan-Meier survival analysis yielded significantly lower survival times for patients in the high-risk group than in the low-risk group, and the AUC values for the ROC curves of this prognostic signature were essentially greater than 0.7, and univariate and multifactorial Cox regression analyses indicated that the risk score was independent risk factors for KIRC prognosis. GSEA analysis showed that immune-related biological processes were enriched in the high-risk group and that risk values were strongly associated with multiple immune cell scores and immune checkpoint-related genes (PDCD1, CTLA4). Conclusions: The prognostic signature can accurately predict the prognosis of KIRC patients, which may provide new ideas for future precision immunotherapy of KIRC.

Application of m6A and TME in Predicting the Prognosis and Treatment of Clear Cell Renal Cell Carcinoma.

Background: Previous studies have shown that RNA N6-methyladenosine (m6A) plays an important role in the construction of the tumor microenvironment (TME). However, how m6A plays a role in the TME of clear cell renal cell carcinoma remains unclear. Methods: Based on 23 m6A modulators, we applied consensus cluster analysis to explore the different m6A modification profiles of ccRCC. The CIBERSORT method was employed to reveal the correlation between TME immune cell infiltration and different m6A modification patterns. A m6A score was constructed using a principal component analysis algorithm to assess and quantify the m6A modification patterns of individual tumors. Results: Three distinct m6A modification patterns of ccRCC were identified. The characteristics of TME cell infiltration in these three patterns were consistent with immune rejection phenotype, immune inflammation phenotype, and immune desert phenotype. In particular, when m6A scores were high, TME was characterized by immune cell infiltration and patient survival was higher (p < 0.05). When m6A scores were low, TME was characterized by immunosuppression and patient survival was lower (p < 0.05). The immunotherapy cohort confirmed that patients with higher m6A scores had significant therapeutic advantages and clinical benefits. Conclusions: The m6A modification plays an important role in the formation of TME. The m6A scoring system allows the identification of m6A modification patterns in individual tumors, discriminates the immune infiltrative features of TME, and provides more effective prognostic indicators and treatment strategies for immunotherapy.