Comparing cohort and period trends of early-onset colorectal cancer: a global analysis.

BACKGROUND: Incidence of early-onset colorectal cancer (EOCRC) has increased globally in recent decades. We examined EOCRC incidence trends worldwide for potential cohort effects, defined as changes associated with time of birth (e.g., early-life exposure to carcinogens), and period effects, defined as changes associated with calendar periods (e.g., screening programs). METHODS: We obtained long-term incidence data for EOCRC diagnosed at age 20-49 through Year 2012 for 35 countries in the Cancer Incidence in Five Continents database. We used a smoothing method to help compare cohort and period trends of EOCRC, and used an age-period-cohort model to estimate cohort and period effects. RESULTS: Cohort effects had a more dominant role than period effects in the EOCRC incidence in Shanghai (China), the United Kingdom, Australia, New Zealand, Canada, the United States, and Osaka (Japan). The smoothed trends show the specific birth cohorts when EOCRC began to increase: the 1940s-1950s birth cohorts in the United States; the 1950s-1960s birth cohorts in other western countries; the 1960s birth cohorts in Osaka (Japan); and the 1970s-1980s birth cohorts in Shanghai (China). Such increases occurred earlier for early-onset cancers of the rectum than the colon. For the other countries, the results were less clear. CONCLUSIONS: Recent birth cohorts may have been exposed to risk factors different than earlier cohorts, contributing to increased EOCRC incidence in several developed countries or regions in the West and Asia. Such increases began in earlier birth cohorts in western countries than in developed regions of Asia.

Diagnosis, treatment, and surveillance of Diamond-Blackfan anaemia syndrome: international consensus statement.

Diamond-Blackfan anaemia (DBA), first described over 80 years ago, is a congenital disorder of erythropoiesis with a predilection for birth defects and cancer. Despite scientific advances, this chronic, debilitating, and life-limiting disorder continues to cause a substantial physical, psychological, and financial toll on patients and their families. The highly complex medical needs of affected patients require specialised expertise and multidisciplinary care. However, gaps remain in effectively bridging scientific discoveries to clinical practice and disseminating the latest knowledge and best practices to providers. Following the publication of the first international consensus in 2008, advances in our understanding of the genetics, natural history, and clinical management of DBA have strongly supported the need for new consensus recommendations. In 2014 in Freiburg, Germany, a panel of 53 experts including clinicians, diagnosticians, and researchers from 27 countries convened. With support from patient advocates, the panel met repeatedly over subsequent years, engaging in ongoing discussions. These meetings led to the development of new consensus recommendations in 2024, replacing the previous guidelines. To account for the diverse phenotypes including presentation without anaemia, the panel agreed to adopt the term DBA syndrome. We propose new simplified diagnostic criteria, describe the genetics of DBA syndrome and its phenocopies, and introduce major changes in therapeutic standards. These changes include lowering the prednisone maintenance dose to maximum 0·3 mg/kg per day, raising the pre-transfusion haemoglobin to 9-10 g/dL independent of age, recommending early aggressive chelation, broadening indications for haematopoietic stem-cell transplantation, and recommending systematic clinical surveillance including early colorectal cancer screening. In summary, the current practice guidelines standardise the diagnostics, treatment, and long-term surveillance of patients with DBA syndrome of all ages worldwide.

Regulatory effect of Yinchenhao decoction on bile acid metabolism to improve the inflammatory microenvironment of hepatocellular carcinoma in mice.

Hepatocellular carcinoma (HCC) is a malignant tumor with extremely high mortality. The tumor microenvironment is the "soil" of its occurrence and development, and the inflammatory microenvironment is an important part of the "soil". Bile acid is closely related to the occurrence of HCC. Bile acid metabolism disorder is not only directly involved in the occurrence and development of HCC but also affects the inflammatory microenvironment of HCC. Yinchenhao decoction, a traditional Chinese medicine formula, can regulate bile acid metabolism and may affect the inflammatory microenvironment of HCC. To determine the effect of Yinchenhao decoction on bile acid metabolism in mice with HCC and to explore the possible mechanism by which Yinchenhao decoction improves the inflammatory microenvironment of HCC by regulating bile acid metabolism, we established mice model of orthotopic transplantation of hepatocellular carcinoma. These mice were treated with three doses of Yinchenhao decoction, then liver samples were collected and tested. Yinchenhao decoction can regulate the disorder of bile acid metabolism in liver cancer mice. Besides, it can improve inflammatory reactions, reduce hepatocyte degeneration and necrosis, and even reduce liver weight and the liver index. Taurochenodeoxycholic acid, hyodeoxycholic acid, and taurohyodeoxycholic acid are important molecules in the regulation of the liver inflammatory microenvironment, laying a foundation for the regulation of the liver tumor inflammatory microenvironment based on bile acids. Yinchenhao decoction may improve the inflammatory microenvironment of mice with HCC by ameliorating hepatic bile acid metabolism.

High-altitude hypoxia exposure inhibits erythrophagocytosis by inducing macrophage ferroptosis in the spleen.

High-altitude polycythemia (HAPC) affects individuals living at high altitudes, characterized by increased red blood cells (RBCs) production in response to hypoxic conditions. The exact mechanisms behind HAPC are not fully understood. We utilized a mouse model exposed to hypobaric hypoxia (HH), replicating the environmental conditions experienced at 6000 m above sea level, coupled with in vitro analysis of primary splenic macrophages under 1% O2 to investigate these mechanisms. Our findings indicate that HH significantly boosts erythropoiesis, leading to erythrocytosis and splenic changes, including initial contraction to splenomegaly over 14 days. A notable decrease in red pulp macrophages (RPMs) in the spleen, essential for RBCs processing, was observed, correlating with increased iron release and signs of ferroptosis. Prolonged exposure to hypoxia further exacerbated these effects, mirrored in human peripheral blood mononuclear cells. Single-cell sequencing showed a marked reduction in macrophage populations, affecting the spleen's ability to clear RBCs and contributing to splenomegaly. Our findings suggest splenic ferroptosis contributes to decreased RPMs, affecting erythrophagocytosis and potentially fostering continuous RBCs production in HAPC. These insights could guide the development of targeted therapies for HAPC, emphasizing the importance of splenic macrophages in disease pathology.

Cancer incidence trends in New York State and associations with common population-level exposures 2010-2018: an ecological study.

The impact of common environmental exposures in combinations with socioeconomic and lifestyle factors on cancer development, particularly for young adults, remains understudied. Here, we leveraged environmental and cancer incidence data collected in New York State at the county level to examine the association between 31 exposures and 10 common cancers (i.e., lung and bronchus, thyroid, colorectal, kidney and renal pelvis, melanoma, non-Hodgkin lymphoma, and leukemia for both sexes; corpus uteri and female breast cancer; prostate cancer), for three age groups (25-49, 50-69, and 70-84 year-olds). For each cancer, we stratified by age group and sex, and applied regression models to examine the associations with multiple exposures simultaneously. The models included 642,013 incident cancer cases during 2010-2018 and found risk factors consistent with previous reports (e.g., smoking and physical inactivity). Models also found positive associations between ambient air pollutants (ozone and PM2.5) and prostate cancer, female breast cancer, and melanoma of the skin across multiple population strata. Additionally, the models were able to better explain the variation in cancer incidence data among 25-49 year-olds than the two older age groups. These findings support the impact of common environmental exposures on cancer development, particularly for younger age groups.

Long-Term Outcomes of dMMR/MSI-H Rectal Cancer Treated With Anti-PD-1-Based Immunotherapy as Curative-Intent Treatment.

BACKGROUND: Neoadjuvant anti-PD-1 therapy has shown encouraging efficacy in patients with deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC), which suggests its potential as a curative-intent therapy and a promising treatment option for organ preservation. We aimed to investigate the long-term outcomes of patients with dMMR/MSI-H LARC who experienced clinical complete response (cCR) after anti-PD-1 therapy. METHODS: We retrospectively analyzed patients with dMMR/MSI-H LARC who achieved cCR and received nonoperative management following neoadjuvant anti-PD-1-based treatment from 4 Chinese medical centers. Patients were followed up for at least 1 year after they achieved cCR, their clinical data were collected, and survival outcomes were analyzed using the Kaplan-Meier method. RESULTS: A total of 24 patients who achieved cCR and received nonoperative management from March 2018 to May 2022 were included, with a median age of 51.0 years (range, 19.0-77.0 years). The median treatment course to reach cCR was 6.0 (range, 1.0-12.0). Fifteen patients (62.5%) continued their treatments after experiencing cCR, and the median treatment course was 17.0 (range, 3.0-36.0). No local regrowth or distant metastasis was observed in a median follow-up time of 29.1 months (range, 12.6-48.5 months) after cCR. The 3-year disease-free and overall survivals were both 100%. CONCLUSIONS: Patients with dMMR/MSI-H locally advanced or low-lying rectal cancer who achieved cCR following anti-PD-1-based therapy had promising long-term outcomes. A prospective clinical trial with a larger sample size is required to further validate these findings.

Effect of deep neuromuscular block on the quality of early recovery after sleeve gastrectomy in obese patients: a randomized controlled trial.

BACKGROUND: Deep neuromuscular block (NMB) has been shown to improve surgical conditions and alleviate post-operative pain in bariatric surgery compared with moderate NMB. We hypothesized that deep NMB could also improve the quality of early recovery after laparoscopic sleeve gastrectomy (LSG). METHODS: Eighty patients were randomized to receive either deep (post-tetanic count 1-3) or moderate (train-of-four count 1-3) NMB. The QoR-15 questionnaire was used to evaluate the quality of early recovery at 1 day before surgery (T0), 24 and 48 h after surgery (T2, T3). Additionally, we recorded diaphragm excursion (DE), postoperative pain, surgical condition, cumulative dose of analgesics, time of first flatus and ambulation, post-operative nausea and vomiting, time of tracheal tube removal and hospitalization time. MAIN RESULTS: The quality of recovery was significantly better 24 h after surgery in patients who received a deep versus moderate block (114.4 ± 12.9 versus 102.1 ± 18.1). Diaphragm excursion was significantly greater in the deep NMB group when patients performed maximal inspiration at T2 and T3 (P < 0.05). Patients who underwent deep NMB reported lower visceral pain scores 40 min after surgery; additionally, these patients experienced lower pain during movement at T3 (P < 0.05). Optimal surgical conditions were rated in 87.5% and 64.6% of all measurements during deep and moderate NMB respectively (P < 0.001). The time to tracheal tube removal was significantly longer in the deep NMB group (P = 0.001). There were no differences in other outcomes. CONCLUSION: In obese patients receiving deep NMB during LSG, we observed improved QoR-15 scores, greater diaphragmatic excursions, improved surgical conditions, and visceral pain scores were lower. More evidence is needed to determine the effects of deep NMB on these outcomes. TRIAL REGISTRATION: ChiCTR2200065919. Date of retrospectively registered: 18/11/2022.

A narrative review of deep learning in thyroid imaging: current progress and future prospects.

Background and Objective: Deep learning (DL) has contributed substantially to the evolution of image analysis by unlocking increased data and computational power. These DL algorithms have further facilitated the growing trend of implementing precision medicine, particularly in areas of diagnosis and therapy. Thyroid imaging, as a routine means to screening for thyroid diseases on large-scale populations, is a massive data source for the development of DL models. Thyroid disease is a global health problem and involves structural and functional changes. The objective of this study was to evaluate the general rules and future directions of DL networks in thyroid medical image analysis through a review of original articles published between 2018 and 2023. Methods: We searched for English-language articles published between April 2018 and September 2023 in the databases of PubMed, Web of Science, and Google Scholar. The keywords used in the search included artificial intelligence or DL, thyroid diseases, and thyroid nodule or thyroid carcinoma. Key Content and Findings: The computer vision tasks of DL in thyroid imaging included classification, segmentation, and detection. The current applications of DL in clinical workflow were found to mainly include management of thyroid nodules/carcinoma, risk evaluation of thyroid cancer metastasis, and discrimination of functional thyroid diseases. Conclusions: DL is expected to enhance the quality of thyroid images and provide greater precision in the assessment of thyroid images. Specifically, DL can increase the diagnostic accuracy of thyroid diseases and better inform clinical decision-making.

Environmental drivers of the rising incidence of early-onset colorectal cancer in the United States.

Incidence of early-onset (diagnosed before age 50) colorectal cancer (EOCRC) has increased alarmingly since the 1990s in the United States. This study investigated what environmental exposures may have driven this increase. We obtained EOCRC incidence data from the Surveillance, Epidemiology, and End Results Program, and data for 11 exposures, for example, body mass index (BMI), from long-term national surveys. We aggregated these data for 30 to 49-year-olds during 1992 to 2016 by population subgroups defined by calendar period, age, race and sex, and used negative binomial regression models to identify and estimate associations of EOCRC with multiple exposures. Furthermore, we used counterfactual modeling to quantify contributions of identified risk factors to EOCRC incidence. The top models (with lowest Bayesian Information Criteria) consistently identified excess body weight, represented by overweight and obesity (BMI ≥25) or obesity alone (BMI ≥30), as the strongest risk factor. The best-performing model estimated increased EOCRC incidence due to overweight and obesity, with an incidence rate ratio (95% confidence interval) of 1.20 (1.17-1.22) for white men, 1.04 (1.00-1.08) for black men, 1.17 (1.15-1.21) for white women and 1.03 (0.97-1.08) for black women. Increases in overweight and obesity prevalence contributed to an estimated 30% (standard error: 1%) for men and 28% (standard error: 2%) for women of ECORC incidence during 1992 to 2016. These findings suggest excess body weight substantially contributed to and is likely a primary driver of the rising incidence of EOCRC in the United States. Prevention of excess weight gain may help lower colorectal cancer risk early in life.

A new cytotoxic disaccharide glycoside from the tubers of Arisaema franchetianum.

A new disaccharide glycoside, franchoside A (1), and 17 known compounds were isolated from the tubers of Arisaema franchetianum Engler. The chemical structure of the previously undescribed compound 1 was elucidated on the basis of detailed spectroscopic analyses. Compounds 1, 2, 6, 10, 14 and 18 showed significant cytotoxic activities at varying IC50 values in the range of 4.0-10.6 µM against five cancer cell lines. Compounds 8, 10, 13 and 17 (10 µM) exhibited moderate anti-inflammatory activities by inhibiting the NF-κB signaling pathway and the release of NO from RAW264.7 macrophages induced by lipopolysaccharide (LPS), while compounds 1, 9, 14, 15 and 16 showed weak anti-inflammatory activities.

A noncovalent backbone planarization strategy increases the NIR-II extinction coefficients for gas/phototheranostic applications.

We propose a noncovalent backbone planarization strategy to fabricate a gas/phototheranostic nanocomposite (B-E-NO NPs) in the near-infrared-II (NIR-II, 1000-1700 nm) window by incorporating noncovalent conformational locks. B-E-NO NPs display a giant NIR-II extinction coefficient, realizing multimodal imaging-guided high-efficiency NIR-II photothermal therapy (η = 45.4%) and thermal-initiated nitric oxide combination therapy.

Exposure to nickel chloride induces epigenetic modification on detoxification enzyme glutathione S-transferase M2.

Nickel (Ni) is a human carcinogen with genotoxic and epigenotoxic effects. Environmental and occupational exposure to Ni increases the risk of cancer and chronic inflammatory diseases. Our previous findings indicate that Ni alters gene expression through epigenetic regulation, specifically impacting E-cadherin and angiopoietin-like 4 (ANGPTL4), involved in epithelial-mesenchymal transition and migration. GST-M2, a member of the glutathione S-transferase (GST) enzyme family, plays a crucial role in cellular defense against oxidative damage and has been increasingly associated with cancer. GST-M2 overexpression inhibits lung cancer invasion and metastasis in vitro and in vivo. Hypermethylation of its promoter in cancer cells reduces gene expression, correlating with poor prognosis in non-small-cell lung cancer patients. The impact of Ni on GST-M2 remains unclear. We will investigate whether nickel exerts regulatory effects on GST-M2 through epigenetic modifications. Additionally, metformin, an antidiabetic drug, is being studied as a chemopreventive agent against nickel-induced damage. Our findings indicate that nickel chloride (NiCl2 ) exposure, both short-term and long-term, represses GST-M2 expression. However, the expression can be restored by demethylation agent 5-aza-2'-deoxycytidine and metformin. NiCl2 promotes hypermethylation of the GST-M2 promoter, as confirmed by methylation-specific PCR and bisulfite sequencing. Additionally, NiCl2 also influences histone acetylation, and metformin counteracts the suppressive effect of NiCl2 on histone H3 expression. Metformin reestablishes the binding of specificity protein 1 to the GST-M2 promoter, which is otherwise disrupted by NiCl2 . These findings elucidate the mechanism by which Ni reduces GST-M2 expression and transcriptional activity, potentially contributing to Ni-induced lung carcinogenesis.

Design and synthesis of the first PARP-1 and proteasome dual inhibitors to treat breast cancer.

PARP-1 is a crucial factor in repairing DNA single strand damage and maintaining genomic stability. However, the use of PARP-1 inhibitors is limited to combination with chemotherapy or radiotherapy, or as a single agent for indications carrying HRR defects. The ubiquitin-proteasome system processes the majority of cellular proteins and is the principal manner by which cells regulate protein homeostasis. Proteasome inhibitors can cooperate with PARP-1 inhibitors to inhibit DNA homologous recombination repair function. In this study, we designed and synthesized the first dual PARP-1 and proteasome inhibitor based on Olaparib and Ixazomib. Both compounds 42d and 42i exhibited excellent proliferation inhibition and dual-target synergistic effects on cells that were insensitive to PARP-1 inhibitors. Further mechanistic evaluations revealed that 42d and 42i could inhibit homologous recombination repair function by down-regulating the expression of BRCA1 and RAD51. Additionally, 42i induced more significant apoptosis and showed better inhibitory effect on cell proliferation in clonal formation experiments in breast cancer cells than 42d. In summary, our study presented a new class of dual PARP-1/proteasome inhibitors with significant synergistic effects for the treatment of breast cancer.

Recovery of valuable metals from spent lithium-ion batteries via zinc powder reduction roasting and cysteine leaching.

With the annual increase in lithium-ion batteries (LIBs) disposal, valuable resources are being generated with worrying waste, so it is strategically important to recover the critical metals from them. Individual high temperature or leaching processes do not apparently achieve very satisfactory results. In the present work, the reduction with zinc powder was able to convert the lithium in LiNixCoyMnzO2 (NCM) to soluble LiOH, while the reduction and ammonia complexation environment generated by the decomposition of cysteine (Cys) achieved an efficient leaching of transition metals without additional additives. The leaching efficiency of Li can reach more than 92 %, while that of Ni/Co/Mn reaches more than 97 % through the regulation of the parameters of each process. In particular, an in-situ redox mechanism is proposed to explain the efficient leaching of transition metals, which further enriches the theory of spent LIBs recycling and provides a promising idea for various hydrometallurgical extraction systems.

HBcrAg-based risk score performs better than the HBV DNA-based scores for HCC prediction in grey zone patients who are HBeAg-negative.

Background & Aims: Risk scores have been designed to predict the development of hepatocellular carcinoma (HCC) in treatment-naive patients with chronic hepatitis B (CHB). However, little is known about their predictive accuracy in HBeAg-negative patients in the grey zone (GZ). We aimed to develop a HBcrAg-based HCC risk score and explore whether it outperforms other risk scores in GZ patients. Methods: Two retrospective cohorts of HBeAg-negative patients with American Association for the Study of Liver Diseases-defined GZ were established for derivation and validation (Taiwanese, N = 911; Japanese, N = 806). All of them were non-cirrhotic at baseline and remained treatment-naive during the follow-up. The primary endpoint was HCC development. Results: In a median follow-up period of 15.5 years, 85 patients developed HCC in the derivation cohort. We found that age, sex, alanine aminotransferase, platelet count, and HBcrAg, but not HBV DNA levels, were independent predictors and a 20-point GZ-HCC score was developed accordingly. The 10-year and 15-year area under the ROC curve (AUROC) ranged from 0.83 to 0.86, which outperformed the HBV DNA-based HCC risk scores, including REACH-B and GAG-HCC scores (AUROC ranging from 0.66 to 0.74). The better performance was also validated in EASL- and Asian Pacific Association for the Study of the Liver-defined GZ patients. These findings remained consistent in the validation cohort. Finally, the low-risk and high-risk GZ patients (stratified by a score of 8) had an HCC risk close to inactive CHB and immune-active CHB patients, respectively, in both cohorts. Conclusions: The HBcrAg-based GZ-HCC score predicts HCC better than other HBV DNA-based risk scores in GZ patients who are HBeAg-negative patients, which may help optimise their clinical management. Impact and implications: We have developed a risk score based on HBcrAg, which has shown better predictive ability for HCC compared with other risk scores based on HBV DNA. Using a score of 8, GZ patients can be classified into low- and high-risk groups, which can guide follow up and early treatment, respectively. This validated risk score is a valuable tool for optimising the management of GZ patients who are HBeAg-negative.

[Gene Mutation Types of Thalassemia in Chongzuo Childbearing-age Population of Guangxi Zhuang Autonomous Region of China].

OBJECTIVE: To investigate the gene mutation and genotype distribution of thalassemia in the population of childbearing age in Chongzuo area of Guangxi. METHODS: Six α-thalassemia and 17 ß-thalassemia gene mutations common in Chinese were detected by gap-polymerase chain reaction (gap-PCR) combined with agarose gel eletrophoresis and reserve dot bolt hybridization in 29 266 cases of child-bearing age suspected of thalassemia. RESULTS: A total of 19 128 (65.36%) cases were identified with thalassemia. The detection rate of α-thalassemia, ß-thalassemia and α-combining ß-thalassemia was 45.25% (13 242/29 266), 15.47% (4 526/29 266) and 4.65% (1 360/29 266), respectively. A total carrying rate of 8 kinds of α-thalassemia gene mutations was 26.74% (15 649/58 532), including 12.51% for --SEA, followed by 5.70% for -α3.7, and 0.24% for --Thai. Among 32 α-thalassemia genotypes, the most common five were --SEA/αα, -α3.7/αα, αCSα/αα, -α4.2/αα and αWSα/αα, accounting for 47.27%, 18.31%, 8.56%, 8.52% and 7.91%, respectively, as well as 0.97% for --Thai/αα. A total carrying rate of 13 kinds of ß-thalassemia gene mutations was 10.07% (5 897/58 532), including 3.63% for CD41-42, followed by 2.55% for CD17, and 0.003% for -50 (G>A). Among 17 ß-thalassemia genotypes, the most common six were CD41-42/N, CD17/N, CD71-72/N, CD26/N, 28/N and IVSI-1/N, accounting for 36.15%, 25.81%, 9.43%, 8.18%, 8.09% and 7.75%. The homozygous genotype CD26/CD26 [hemoglobin (Hb): 121 g/L] and -28/-28 (Hb: 56 g/L) were respectively detected in one case, and double heterozygous genotype were detected in 5 cases, including 3 cases of CD41-42/CD26 (Hb: 41 g/L, 51 g/L, 63 g/L, respectively), 1 case of -28/IVSI-1 (Hb: 53 g/L), and 1 case of CD71-72/CD26 (Hb: 89 g/L), in which patients with moderate or severe anemia had a history of blood transfusion. Among 104 α-combining ß-thalassemia genotypes, the most common were --SEA/αα, -α3.7/αα combining CD41-42/N and --SEA/αα combining CD17/N, accounting for 12.13%, 9.63% and 9.26%, respectively. In addition, 1 case of --SEA/-α3.7 combining -28/IVSI-1 (Hb: 83 g/L) and 1 case of -α3.7/αα combining CD41-42/ CD41-42 (Hb: 110 g/L) were detected without history of blood transfusion, while 1 case of αWSα/αα combining CD41-42/CD17 (Hb: 79 g/L) and 1 case of --SEA/αα combining CD17/-28 (Hb: 46 g/L) were detected with history. CONCLUSIONS: The detection rate of thalassemia genes is high and the mutations are diverse in the population of childbearing age in Chongzuo area of Guangxi. The common deletion genotype is --SEA/αα in α-thalassemia and CD41-42/N in ß-thalassemia, and deletion genotype --Thai is not rare. There is a certain incidence of intermediate and severe ß-thalassemia, and most patients require transfusion therapy. The results are beneficial for genetic consultation and intervention of thalassemia.

Near infrared II excitation nanoplatform for photothermal/chemodynamic/antibiotic synergistic therapy combating bacterial biofilm infections.

Drug-resistant bacterial biofilm infections (BBIs) are refractory to elimination. Near-infrared-II photothermal therapy (NIR-II PTT) and chemodynamic therapy (CDT) are emerging antibiofilm approaches because of the heavy damage they inflict upon bacterial membrane structures and minimal drug-resistance. Hence, synergistic NIR-II PTT and CDT hold great promise for enhancing the therapeutic efficacy of BBIs. Herein, we propose a biofilm microenvironment (BME)-responsive nanoplatform, BTFB@Fe@Van, for use in the synergistic NIR-II PTT/CDT/antibiotic treatment of BBIs. BTFB@Fe@Van was prepared through the self-assembly of phenylboronic acid (PBA)-modified small-molecule BTFB, vancomycin, and the CDT catalyst Fe2+ ions in DSPE-PEG2000. Vancomycin was conjugated with BTFB through a pH-sensitive PBA-diol interaction, while the Fe2+ ions were bonded to the sulfur and nitrogen atoms of BTFB. The PBA-diol bonds decomposed in the acidic BME, simultaneously freeing the vancomycin and Fe2+ irons. Subsequently, the catalytic product hydroxyl radical was generated by the Fe2+ ions in the oxidative BME overexpressed with H2O2. Moreover, under 1064 nm laser, BTFB@Fe@Van exhibited outstanding hyperthermia and accelerated the release rate of vancomycin and the efficacy of CDT. Furthermore, the BTFB@Fe@Van nanoplatform enabled the precise NIR-II imaging of the infected sites. Both in-vitro and in-vivo experiments demonstrated that BTFB@Fe@Van possesses a synergistic NIR-II PTT/CDT/antibiotic mechanism against BBIs.

GNAS locus: bone related diseases and mouse models.

GNASis a complex locus characterized by multiple transcripts and an imprinting effect. It orchestrates a variety of physiological processes via numerous signaling pathways. Human diseases associated with the GNAS gene encompass fibrous dysplasia (FD), Albright's Hereditary Osteodystrophy (AHO), parathyroid hormone(PTH) resistance, and Progressive Osseous Heteroplasia (POH), among others. To facilitate the study of the GNAS locus and its associated diseases, researchers have developed a range of mouse models. In this review, we will systematically explore the GNAS locus, its related signaling pathways, the bone diseases associated with it, and the mouse models pertinent to these bone diseases.

SFTSV Gn-Head mRNA vaccine confers efficient protection against lethal viral challenge.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus, causing thrombocytopenia and hemorrhagic fever, with a fatality rate ranging from 12% to 30%. SFTSV possesses Gn and Gc glycoproteins, which are responsible for host cell receptor attachment and membrane fusion, respectively, to infect host cells. We have previously reported a protein subunit vaccine candidate (sGn-H-FT) of the SFTSV soluble Gn head region (sGn-H) fused with self-assembling ferritin (FT) nanoparticles, displaying strong protective immunogenicity. In this study, we present messenger RNA (mRNA) vaccine candidates encoding sGn-H or sGn-H-FT, both of which exhibit potent in vivo immunogenicity and protection capacity. Mice immunized with either sGn-H or sGn-H-FT mRNA lipid nanoparticle (LNP) vaccine produced strong total antibodies and neutralizing antibodies (NAbs) against sGn-H. Importantly, NAb titers remained high for an extended period. Finally, mice immunized with sGn-H or sGn-H-FT mRNA LNP vaccine were fully protected from a lethal dose of SFTSV challenge, showing no fatality. These findings underscore the promise of sGn-H and sGn-H-FT as vaccine antigen candidates capable of providing protective immunity against SFTSV infection.

Carbon Ion Radiotherapy: An Evidence-Based Review and Summary Recommendations of Clinical Outcomes for Skull-Base Chordomas and Chondrosarcomas.

Skull-base chordoma and chondrosarcoma are rare radioresistant tumors treated with surgical resection and/or radiotherapy. Because of the established dosimetric and biological benefits of heavy particle therapy, we performed a systematic and evidence-based review of the clinical outcomes of patients with skull-base chordoma and chondrosarcoma treated with carbon ion radiotherapy (CIRT). A literature review was performed using a MEDLINE search of all articles to date. We identified 227 studies as appropriate for review, and 24 were ultimately included. The published data illustrate that CIRT provides benchmark disease control outcomes for skull-base chordoma and chondrosarcoma, respectively, with acceptable toxicity. CIRT is an advanced treatment technique that may provide not only dosimetric benefits over conventional photon therapy but also biologic intensification to overcome mechanisms of radioresistance. Ongoing research is needed to define the magnitude of benefit, patient selection, and cost-effectiveness of CIRT compared to other forms of radiotherapy.