Reprogramming Tumor-Associated Macrophages with a Se-Based Core-Satellite Nanoassembly to Enhance Cancer Immunotherapy.

Tumor-associated macrophages (TAMs), as the most prevalent immune cells in the tumor microenvironment, play a pivotal role in promoting tumor development through various signaling pathways. Herein, we have engineered a Se@ZIF-8 core-satellite nanoassembly to reprogram TAMs, thereby enhancing immunotherapy outcomes. When the nanoassembly reaches the tumor tissue, selenium nanoparticles and Zn2+ are released in response to the acidic tumor microenvironment, resulting in a collaborative effort to promote the production of reactive oxygen species (ROS). The generated ROS, in turn, activate the nuclear factor κB (NF-κB) signaling pathway, driving the repolarization of TAMs from M2-type to M1-type, effectively eliminating cancer cells. Moreover, the nanoassembly can induce the immunogenic death of cancer cells through excess ROS to expose calreticulin and boost macrophage phagocytosis. The Se@ZIF-8 core-satellite nanoassembly provides a potential paradigm for cancer immunotherapy by reversing the immunosuppressive microenvironment.

Neuroprotection and mechanisms of ginsenosides in nervous system diseases: Progress and perspectives.

Ginsenosides are the primary component discernible from ginseng, including Rb1, Rb2, Rd, Rg1, Rg2, and compound K, and so forth. They have been shown to have multiple pharmacological activities. In recent years, more and more studies have been devoted to the neuroprotection of various ginsenosides against neurological diseases and their potential mechanisms. This paper comprehensively summarizes and reviews the neuroprotective effects of various ginsenosides on neurological diseases, especially acute and chronic neurodegenerative diseases, and their mechanisms, as well as their potential therapeutic applications to promote neuroprotection in disease prevention, treatment, and prognosis. Briefly, ginsenosides exert effective neuroprotective effects on neurological conditions, including stroke, Alzheimer's disease, Parkinson's disease, and brain/spinal cord injuries through a variety of molecular mechanisms, including anti-inflammatory, antioxidant, and anti-apoptotic. Among them, some signaling pathways play important roles in related processes, such as PI3K/Akt, TLR4/NF-κB, ROS/TXNIP/NLRP3, HO-1/Nrf2, Wnt/ß-catenin, and Ca2+ pathway. In conclusion, the present study reviews the research progress on the neuroprotective effects of ginsenosides in the last decade, with the aim of furnishing essential theoretical underpinning and effective references for further research and exploration of the multiple medicinal values of Chinese herbal medicines and their small molecule compounds, including ginseng and panax ginseng. Because there is less evidence in the existing clinical studies, future research should be focused on clinical trials in order to truly reflect the clinical value of various ginsenosides for the benefit of patients.

The relationship between resistance evolution and carbon metabolism in Staphylococcus xylosus under ceftiofur sodium stress.

Staphylococcus xylosus has emerged as a bovine mastitis pathogen with increasing drug resistance, resulting in substantial economic impacts. This study utilized iTRAQ analysis to investigate the mechanisms driving resistance evolution in S. xylosus under ceftiofur sodium stress. Findings revealed notable variations in the expression of 143 proteins, particularly glycolysis-related proteins (TpiA, Eno, GlpD, Ldh) and peptidoglycan (PG) hydrolase Atl. Following the induction of ceftiofur sodium resistance in S. xylosus, the emergence of resistant strains displaying characteristics of small colony variants (SCVs) was observed. The transcript levels of TpiA, Eno, GlpD and Ldh were up-regulated, TCA cycle proteins (ICDH, MDH) and Atl were down-regulated, lactate content was increased, and NADH concentration was decreased in SCV compared to the wild strain. That indicates a potential role of carbon metabolism, specifically PG hydrolysis, glycolysis, and the TCA cycle, in the development of resistance to ceftiofur sodium in S. xylosus.

Apheresis practice variation during the COVID-19 pandemic: Results of a survey.

BACKGROUND: The COVID-19 pandemic affected healthcare delivery across all specialties including apheresis. To describe the changes in apheresis service practices that occurred during the pandemic, the American Society for Apheresis (ASFA) Apheresis Medicine Attending Physician Subcommittee conducted a survey study. STUDY DESIGN AND METHODS: A 32-question survey was designed and distributed to 400 ASFA physician members on September 7, 2022. Attending physicians responded to questions about whether and how apheresis service practices changed during the COVID-19 pandemic compared with the time period prior to the pandemic in terms of: (1) procedure types and volumes, (2) patient consultation workflow, and (3) the use of telemedicine. Descriptive analyses were reported as number and frequency of responses. RESULTS: The survey response rate was 13.8% (55/400). Of these respondents, 96.4% (53/55) were attending physicians. The majority of respondents (42/53, 79.2%) indicated that the types of procedures performed during COVID-19 compared to pre-pandemic did not change. Most frequently for apheresis procedure volume, respondents reported: no change in their monthly inpatient volume (21/47, 44.7%) and a decrease in their monthly outpatient volume (28/46, 60.9%). Prior to COVID-19, 75.0% (30/40) of respondents performed consultations at bedside for inpatients and 67.4% (29/43) performed consultations at bedside for outpatients. Bedside consultations decreased in both settings during the pandemic but were still most frequently performed by attending physicians. At the same time, the use of telemedicine increased for 15.4% of survey respondents during COVID-19. CONCLUSION: Some, but not all, respondents observed or made changes to their apheresis service during the COVID-19 pandemic. A subset of changes, such as increased utilization of telemedicine, may persist.

Fine Mapping of Five Grain Size QTLs Which Affect Grain Yield and Quality in Rice.

Grain size is a quantitative trait with a complex genetic mechanism, characterized by the combination of grain length (GL), grain width (GW), length to width ration (LWR), and grain thickness (GT). In this study, we conducted quantitative trait loci (QTL) analysis to investigate the genetic basis of grain size using BC1F2 and BC1F2:3 populations derived from two indica lines, Guangzhan 63-4S (GZ63-4S) and TGMS29 (core germplasm number W240). A total of twenty-four QTLs for grain size were identified, among which, three QTLs (qGW1, qGW7, and qGW12) controlling GL and two QTLs (qGW5 and qGL9) controlling GW were validated and subsequently fine mapped to regions ranging from 128 kb to 624 kb. Scanning electron microscopic (SEM) analysis and expression analysis revealed that qGW7 influences cell expansion, while qGL9 affects cell division. Conversely, qGW1, qGW5, and qGW12 promoted both cell division and expansion. Furthermore, negative correlations were observed between grain yield and quality for both qGW7 and qGW12. Nevertheless, qGW5 exhibited the potential to enhance quality without compromising yield. Importantly, we identified two promising QTLs, qGW1 and qGL9, which simultaneously improved both grain yield and quality. In summary, our results laid the foundation for cloning these five QTLs and provided valuable resources for breeding rice varieties with high yield and superior quality.

[Clinical and genetic analysis of a Chinese patient with Alström syndrome].

OBJECTIVE: To explore the genetic etiology for a patient with Alström syndrome (ALMS) presenting as dilated cardiomyopathy. METHODS: A 41-year-old male patient who had presented at the Sixth Medical Center of PLA General Hospital on October 20, 2021 was selected as the study subject. Clinical and laboratory examinations were carried out. Whole exome sequencing (WES) was employed for genetic testing, and candidate variants were validated by Sanger sequencing and pathogenicity analysis. RESULTS: The patient had a 14-year medical history characterized by dilated cardiomyopathy, complete atrioventricular block, visual impairment, sensorineural hearing loss, truncal obesity, insulin resistance, type 2 diabetes, hypertension, renal dysfunction, and paranoid delusions. Genetic testing revealed that he has harbored compound heterozygous variants of the ALMS1 gene, namely c.6823C>T (p.Arg2275Ter) and c.9442_9445dup (p.Ser3149LysfsTer2). Sanger sequencing confirmed that they were inherited from his father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1_VeryStrong+PM2_Supporting+PM3+PP3, PVS1_VeryStrong+PM2_Supporting+PM3). Literature review indicated that the complete atrioventricular block in the patient was a phenotype unreported previously. CONCLUSION: The c.6823C>T (p.Arg2275Ter) and c.9442_9445dup (p.Ser3149LysfsTer2) compound heterozygous variants of the ALMS1 gene probably underlay the pathogenesis in this patient. Above findings have expanded the phenotypic spectrum of ALMS and provided insights for clinicians dealing with similar cases.

[Clinical Efficacy of Anchor Suture Bridge Technique for Avulsion Fractures of the Posterior Cruciate Ligament Tibial Insertion Point in the Knee Joint]. / é”šé’‰ç¼çº¿æ¡¥æŠ€æœ¯å¯¹è†å ³èŠ‚åŽäº¤å‰éŸ§å¸¦èƒ«éª¨æ­¢ç‚¹æ’•è„±éª¨æŠ˜çš„ä¸´åºŠç–—æ•ˆ.

Objective: To investigate the clinical efficacy of the anchor suture bridge technique in treating avulsion fractures at the tibial insertion point of the posterior cruciate ligament (PCL) in the knee joint. Methods: In this study, we reviewed 80 patients with PCL tibial avulsion fractures treated using the anchor suture bridge technique in our department from February 2010 to December 2023. Follow-ups were conducted starting at 3 months post-surgery, then every 3 months until 12 months post-surgery. Clinical and follow-up data of each patient were analyzed. The Lysholm and Hospital for Special Surgery Knee-Rating Scale (HSS) scores of knee function before surgery and at the last follow-up were compared to assess the surgical treatment outcome. Results: The 80 patients were followed up for an average of (12.16±1.08) months post-surgery. Re-examination X-rays showed that all fractures had healed, with an average healing time of (3.66±0.51) months. All patients recovered well, with primary healing of surgical incisions and no complications such as neurovascular injury, skin necrosis, incision infection, fracture displacement, or ligament laxity. Postoperative knee Lysholm and HSS scores were significantly higher than preoperative scores. At the last follow-up, the Lysholm score increased from (46.30±6.10) preoperatively to (90.85±3.27), and the HSS score increased from (45.30±5.80) to (91.15±2.66), with statistically significant differences (P<0.025). Conclusion: The anchor suture bridge technique is effective in treating avulsion fractures of the PCL tibial insertion point in the knee joint. It has a high safety profile and leads to good postoperative knee function recovery, with no serious postoperative complications, demonstrating excellent clinical efficacy.

Changes in Early T-Cell Subsets and Their Impact on Prognosis in Patients with Sepsis: A Single-Center Retrospective Study.

Objective: To analyze the early changes in CD3+, CD4+, and CD8+T-cell subset counts in patients with sepsis and their correlation with prognosis to provide a feasible basis for clinical immunomodulation in sepsis. Methods: This is a single-center retrospective study. The study enrolled sepsis patients (meeting SEPSIS 3.0 definition) who were admitted to the Department of Intensive Care Unit at the First Hospital of Jilin University from July 5th, 2018 to December 5th, 2019 and were aged 18 years or above. In addition, these patients underwent cellular immune testing (CD3+, CD4+, CD8+ T lymphocyte counts, and CD4+/CD8+ ratio) within 24 hours of ICU admission. Patient's clinical data including age, gender, infection site, APACHE II score, SOFA score, length of ICU stay, mechanical ventilation time, ICU mortality, 28-day mortality, and 3-year survival status were collected. The prognostic indicators and survival of the decreased and nondecreased groups of different subsets of T lymphocyte counts and CD4+/CD8+ ratio were compared. Results: A total of 206 patients were enrolled, with 76.7% having a decrease in CD3+ T lymphocyte count, 76.7% having a decrease in CD4+ T lymphocyte count, and 63.6% having a decrease in CD8+ T lymphocyte count. Furthermore, 21.8% had a lower CD4+/CD8+ ratio. Analysis showed that the CD3+ T lymphocyte count decreased group had a longer length of ICU stay [11 d (4, 21) vs. 7 d (4, 17), P=0.03], increased percentage of mechanical ventilation (67.5% vs. 51.0%, P=0.04), and extended mechanical ventilation time [144 h (48, 360) vs. 96 h (48, 144), P=0.04] compared to the nondecreased group. The 28-day mortality was higher in the decreased group of CD4+/CD8+ ratio compared to the nondecreased group (33.3% vs. 25.5%, P=0.29); however, the difference did not reach statistical significance. Logistic regression analysis revealed no significant correlation between the decrease in CD4+/CD8+ ratio and 28-day mortality (P=0.11). The 3-year follow-up revealed that the CD4+/CD8+ decreased group had a lower survival rate than the nondecreased group (33.3% vs. 53.4%, P=0.01). Conclusions: In the early stage of sepsis, most patients showed a decrease in CD3+, CD4+, and CD8+T-cell subsets, as well as in the CD4+/CD8+ ratio. The decrease in CD3+ and CD4+/CD8+ was related to some poor prognosis.

Effects of parietal repetitive transcranial magnetic stimulation in prolonged disorders of consciousness: A pilot study.

Objective: Although the parietal cortex is related to consciousness, the dorsolateral prefrontal and primary motor cortices are the usual targets for repetitive transcranial magnetic stimulation (rTMS) for prolonged disorders of consciousness (pDoC). Herein, we applied parietal rTMS to patients with pDoC, to verify its neurobehavioral effects and explore a new potential rTMS target. Materials and methods: Twenty-six patients with pDoC were assigned to a rTMS or sham group. The rTMS group received 10 sessions of parietal rTMS; the sham group received 10 sessions of sham stimulation. The Coma Recovery Scale-Revised (CRS-R) and event-related potential (ERP) were collected before and after the 10 sessions or sham sessions. Results: After the 10 sessions, the rTMS group showed: a significant CRS-R score increase; ERP appearance of a P300 waveform and significantly increased Fz amplitudes; increased potentials on topographic mapping, especially in the left prefrontal cortex; and an increase in delta and theta band powers at Fz, Cz, and Pz. The sham group did not show such changes in CRS-R score or ERP results statistically. Conclusion: Parietal rTMS shows promise as a novel intervention in the recovery of consciousness in pDoC. It showed neurobehavioral enhancement of residual brain function and may promote frontal activity by enhancing frontal-parietal connections. The parietal cortex may thus be an alternative for rTMS therapy protocols.

Positive Development Patterns in Left-Behind Adolescents: Do Resilience and Making Sense of Adversity Have Beneficial Effects?

Purpose: Despite increased attention to the positive development of left-behind adolescents, research findings remain inconclusive. Utilizing latent profile analysis, we identified various positive development profiles among the left-behind adolescents and explored the association between resilience and positive development profiles, alongside the mediating role of making sense of adversity. Methods: A multi-stage cluster sampling procedure was employed, randomly selecting four provinces-Zhejiang, Guangdong, Henan, and Jiangxi-from the central and coastal regions. The sample comprised 718 left-behind adolescents recruited from primary and junior high schools across grades 4, 5, 7, and 8. Three scales were utilized, and analyses included latent profile analysis and mediation analysis. Results: Three latent subgroups of positive development among left-behind adolescents were identified: low, moderate, and high. Those with higher resilience and positive perceptions of adversity tended to belong to the high group rather than the low (ß = -0.45, p < 0.001; ß = -0.09, p < 0.001) or moderate group (ß = -0.23, p < 0.001; ß = -0.04, p < 0.05). Left-behind adolescents with higher negative perceptions of adversity tended to belong to the high group rather than the moderate group (ß = -0.07, p < 0.01). Mediation analysis revealed that resilience facilitated the development of positive appraisals of adversity, subsequently increasing the likelihood of being categorized into the high (95% CI of -0.09 to -0.03) or moderate group (95% CI of -0.05 to -0.01) rather than the low group. Conclusion: These findings hold significant implications for intervention formulation. Educators should focus on strengthening resilience and fostering positive perceptions of adversity among the low group. For the moderate group, maintaining moderate negative perceptions of adversity may stimulate the intrinsic potential for positive development more effectively.

An update on noninvasive neuromodulation in the treatment of patients with prolonged disorders of consciousness.

BACKGROUND: With the improvement of emergency techniques, the survival rate of patients with severe brain injury has increased. However, this has also led to an annual increase in the number of patients with prolonged disorders of consciousness (pDoC). Hence, recovery of consciousness is an important part of treatment. With advancing techniques, noninvasive neuromodulation seems a promising intervention. The objective of this review was to summarize the latest techniques and provide the basis for protocols of noninvasive neuromodulations in pDoC. METHODS: This review summarized the advances in noninvasive neuromodulation in the treatment of pDoC in the last 5 years. RESULTS: Variable techniques of neuromodulation are used in pDoC. Transcranial ultrasonic stimulation (TUS) and transcutaneous auricular vagus nerve stimulation (taVNS) are very new techniques, while transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) are still the hotspots in pDoC. Median nerve electrical stimulation (MNS) has received little attention in the last 5 years. CONCLUSIONS: Noninvasive neuromodulation is a valuable and promising technique to treat pDoC. Further studies are needed to determine a unified stimulus protocol to achieve optimal effects as well as safety.

Traffic noise distribution characteristics of high-rise buildings along ultra-wide cross section highway with multiple noise reduction measures.

Nowadays, ultra-wide cross section highway is a hotspot in construction and brings some unique noise distribution characteristics. In this work, we further investigate noise distribution characteristics of diverse building layouts along ultra-wide cross section highway in Guangdong Province with multiple noise mitigation measures. By the aid of vehicle noise emission model and noise mapping, the influence of high-rise building layouts and shielding in the urban planning on noise mitigation is also considered. Some key findings are summarized as follows: (1) Under the same distance, the noise level of non-frontage building facades is higher than frontage building facades. After taking noise reduction measures, the noise reduction effect of non-street-facing building facades, buildings facing the road, and buildings at a long distance to the road is greater than street-facing building facades, buildings sideways to the road, and buildings at a short distance; (2) the distribution trend of insertion loss (IL) of non-frontage buildings is influenced by the height of the frontage buildings. Specifically, the trend of insertion loss first increases and then decreases as the floor rises when the height of non-frontage buildings is higher than frontage buildings. Comparatively, the trend of insertion loss decreases as the floor rises when the height of non-frontage buildings is equal to frontage buildings; (3) when double noise reduction measures are implemented, the noise distribution trend in buildings is similar to that observed with individual noise reduction measure, where the difference between both is only 0.6 dB(A). Thanks to the high representativeness of the case area, this work can provide some design guidance for the urban planning and the selection of noise reduction measures along the ultra-wide cross section highway.

Enteral feeding strategies in patients with acute gastrointestinal injury: From limited to progressive to open feeding.

Acute gastrointestinal injury (AGI) is very common in critically ill patients, and its severity is positively correlated with mortality. Critically ill patients with digestive and absorption dysfunction caused by AGI face higher nutritional risks, making nutritional support particularly important. Early enteral nutrition (EN) support is extremely important because it can promote the recovery of intestinal function, protect the intestinal mucosal barrier, reduce microbiota translocation, reduce postoperative complications, shorten hospital stay, and improve clinical prognosis. In recent years, many nutritional guidelines have been proposed for critically ill patients; however, there are few recommendations for the implementation of EN in patients with AGI, and their quality of evidence is low. The use of EN feeding strategies in critically ill patients with AGI remains controversial. The aim of this review was to elaborate on how EN feeding strategies should transition from limited to progressive to open feeding and explain the time window for this transition.

Causal roles and clinical utility of cardiovascular proteins in colorectal cancer risk: a multi-modal study integrating mendelian randomization, expression profiling, and survival analysis.

PURPOSE: This comprehensive investigation delved into the intricate causal interplay existing between cardiovascular-related plasma proteins and the susceptibility to colorectal cancer, leveraging the robust framework of Mendelian randomization, and employed expression profiling and survival analysis to unravel the latent clinical worth embedded within pertinent gene expressions. METHODS: Protein quantitative trait loci (pQTLs) of 85 cardiovascular proteins were employed as instrumental variables to investigate the causal relationship between proteins and CRC risk using a Mendelian randomization approach. Causal inferences were graded as strong, intermediate or weak based on statistical checks. Drug-target MR examined VEGF receptors for their potential as therapeutic targets for colorectal cancer. Differential expression analysis, diagnostic ROC curves, and survival analyses were performed for identified proteins using RNA-seq data from The Cancer Genome Atlas (TCGA) colorectal cancer cohort. RESULTS: Using cis-pQTLs, LOX-1, VEGF-A and OPG were associated with increased CRC risk (strong evidence), while PTX3, TNF-R2 and MMP-7 were protective (strong evidence). Pan-pQTL analysis found MMP-10 increased risk (intermediate evidence) and ADM increased risk (weak evidence). Drug-target MR found VEGF R1 may be promising therapeutic targets. Differential expression analysis revealed seven genes encoding the identified proteins were dysregulated in tumors. ROC analysis showed five gene expression had high diagnostic accuracy. KM analysis showed four genes had prognostic value. CONCLUSIONS: This large-scale MR study implicates several cardiovascular proteins in CRC susceptibility and progression. Findings highlight roles for VEGF signaling and extracellular matrix regulation. Results nominate specific proteins as potential diagnostic biomarkers or therapeutic targets warranting further investigation.

Antioxidant properties and changes in vitro digestion of the fermented kiwifruit extract prepared by lactic acid bacteria and yeasts.

The health benefits of fermented fruits have attracted consumers' attention. High levels of antioxidant ability in the fermented kiwifruit extract were found at the early stage of fermentation. The co-fermention with Lactobacillus paracasei LG0260 and Kluyveromyces marxianus J2853 showed the highest ABTS radical scavenging ability (ABTS⋅+-SA) and superoxide dismutase (SOD) activity. Also, the typical antioxidant components of SOD activity, vitamin C concentration and total phenol content were highly correlated with ABTS⋅+-SA. Obviously, polyphenols in the fermented kiwifruit extract evolved into monophenols during fermentation. Compared to undigested samples, the activity of ABTS⋅+-SA and reducing power capacity (RP-CA) after the final intestinal digestion decreased and ranged 387.44-531.89 VCµg/mL, 650.95-981.63 VCµg/mL, respectively (P < 0.05). Meanwhile, SOD activity on the 10th day of fermentation were still remained 222.82 U/mL, 206.98 U/mL and 217.23 U/mL, respectively. These results suggested that the fermented kiwifruit extract could exhibit antioxidant activity through tolerance to the digestive environment.

Research and exploration of quality control indicators for nutritional therapy in critically ill patients-a multicenter before-and-after controlled study.

Objective: To evaluate and explore the feasibility of using quality control indicators for nutritional therapy in critically ill patients as quality evaluation criteria. Methods: This study focused on intensive care unit (ICU) critically ill patients and conducted a cross-sectional investigation of nutritional therapy quality control indicators (the proportion of patients with application of enteral nutrition pump, nutritional risk assessment rate, the proportion of patients start enteral nutrition within 48 hours, and caloric and protein target achievement rate on 7th day) in 13 hospitals in Jilin Province. After training according to the critical patients nutrition related guidelines and the latest literatures, a second cross-sectional investigation was conducted. Then, analyze the improvement of quality control indicators of the nutritional therapy before and after the training, thus evaluating the feasibility of using these quality control indicators as nutritional therapy quality evaluation criteria in critical patients. Results: (1) A total of 631 patients were included before and after training, with a data acquisition rate of 97.3% for enteral nutrition pumps usage and complete data collection for the remaining nutritional risk assessment rate, start enteral nutrition proportion of patients within 48 h, and caloric and protein target achievement rate on 7th day. (2) The nutritional risk assessment rate before and after training was 88.2% vs. 94.8%, with a P-value of 0.003. The proportion of patients start enteral nutrition within 48 h before and after training was 65.1% vs. 75.4%, with a P-value of 0.039; and protein target achievement rate on 7th day before and after training was 64.6% vs. 79.6%, with a p-value of 0.015. These five indicators as quality evaluation criteria are relevant to the current developments in nutritional therapy and consistent with the national conditions of China. The proportion of patients with application of enteral nutrition pump before and after training was 70.1% vs. 79.4%, with a p-value of 0.065, and the caloric target achievement rate on 7th day before and after training was 73.4% vs. 83.9%, with a p-value of 0.062, and there was no statistical difference between the two groups. Conclusion: The five quality control indicators for nutritional therapy in critically ill patients are clinically feasible and can be used as quality evaluation criteria for nutritional therapy in critically ill patients.

A GalNAc-modified CaCO3 nano-immunomodulator for targeted and responsive immunotherapy against orthotopic liver cancer.

A nano-immunomodulator modified with N-acetylgalactosamine (GalNAc) on calcium carbonate (CaCO3) was prepared for targeted and responsive immunotherapy. And the immunologic adjuvant (CpG ODNs) and doxorubicin (DOX) were released to synergistically improve immune response for treating orthotopic liver cancer.

Organelle-based immunotherapy strategies for fighting against cancer.

Destruction of subcellular organelles can cause dysfunction and even death of cells to elicit immune responses. In this review, the characteristics and functions of important organelles are mainly summarized. Then, the intelligent immunotherapeutic strategies and suggestions based on influencing the organelles are further highlighted. This review will provide ideas for developing novel and effective immunotherapy strategies and advance the development of cancer immunotherapy.

Exogenous methionine contributes to reversing the resistance of Streptococcus suis to macrolides.

Streptococcus suis (S. suis) has been increasingly recognized as a porcine zoonotic pathogen that threatens the health of both pigs and humans. Multidrug-resistant Streptococcus suis is becoming increasingly prevalent, and novel strategies to treat bacterial infections caused by these organisms are desperately needed. In the present study, an untargeted metabolomics analysis showed that the significant decrease in methionine content and the methionine biosynthetic pathway were significantly affected by the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis in drug-resistant S. suis. The addition of L-methionine restored the bactericidal activity of macrolides, doxycycline, and ciprofloxacin on S. suis in vivo and in vitro. Further studies showed that the exogenous addition of methionine affects methionine metabolism by reducing S-adenosylmethionine synthetase activity and the contents of S-adenosylmethionine, S-adenosyl homocysteine, and S-ribose homocysteine. Methionine can decrease the total methylation level and methylesterase activity in multidrug resistant S. suis. The drug transport proteins and efflux pump genes were significantly downregulated in S. suis by exogenous L-methionine. Moreover, the exogenous addition of methionine can reduce the survival of S. suis by affecting oxidative stress and metal starvation in bacteria. Thus, L-methionine may influence the development of resistance in S. suis through methyl metabolism and metal starvation. This study provides a new perspective on the mitigation of drug resistance in S. suis.IMPORTANCEBacterial antibiotic resistance has become a severe threat to human and animal health. Increasing the efficacy of existing antibiotics is a promising strategy against antibiotic resistance. Here, we report that L-methionine enhances the efficacy of macrolides, doxycycline, and ciprofloxacin antibiotics in killing Streptococcus suis, including multidrug-resistant pathogens. We investigated the mechanism of action of exogenous methionine supplementation in restoring macrolides in Streptococcus suis and the role of the methionine cycle pathway on methylation levels, efflux pump genes, oxidative stress, and metal starvation in Streptococcus suis. It provides a theoretical basis for the rational use of macrolides in clinical practice and also identifies a possible target for restoring drug resistance in Streptococcus suis.