Phototherapy such as photothermal therapy and photodynamic therapy in cancer treatment has been developed quickly over the past few years for its noninvasive nature and high efficiency. However, there are still many drawbacks in phototherapy that prevent it from clinical applications. Thus, scientists have designed different systems to overcome the issues associated with phototherapy, including enhancing the targeting ability of phototherapy, low‐temperature photothermal therapy, replacing near‐infrared light with other excitation sources, and so on. This article discusses the problems and shortcomings encountered in the development of phototherapy and highlights possible solutions to address them so that phototherapy may become a useful cancer treatment approach in clinical practice. This article aims to give a brief summary about current research advancements in phototherapy research and provides a quick guideline toward future developments in the field.

To comprehensively analyze the global level and trends of prevalence, incidence and years lived with disability (YLDs) for low back pain (LBP) from 1990 to 2019 by age, sex and sociodemographic index (SDI). Publicly available modelled data and methods were obtained from the Global Burden of Diseases (GBD) study 2019, and used to evaluate the global burden of LBP through a systematic analysis. Globally, the age-standardized prevalence, incidence and YLDs rate of LBP were slightly decreased from 1990 to 2019, but the number of the prevalent cases, incident cases and YLDs had substantially increased, and LBP remains the leading cause of YLDs in 2019 worldwide. The number of prevalent cases was increased with age and peaked at the age of 45–54 years for both sexes, and the global prevalence rate was higher in females than in males and increased with age, peaking at the 80–84 age group in both sexes in 2019. Overall, a positive association between the age-standardized YLD rate and SDI was observed over the past thirty years. At the national revel, the United States, Denmark and Switzerland had the three highest levels of age-standardized prevalence, while Zambia, Zimbabwe and Canada showed the highest increase in the age-standardized prevalence during 1990–2019. LBP is a major public health issue globally, and its burden remains high. Increasing population awareness about its risk factors and preventive measures for LBP are needed to reduce the future burden of this condition. Due to the high prevalence and heavy burden of LBP globally, it is important to update its epidemiological data. This systematic analysis provides researchers and healthcare policy makers with up-to-date, comprehensive and comparable information on global LBP burden, which is of clinical translational significance.

Background: Recently, the association between inflammatory bowel disease (including ulcerative colitis and Crohn’s disease) and BMD has attracted great interest in the research community. However, the results of the published epidemiological observational studies on the relationship between inflammatory bowel disease and BMD are still inconclusive. Here, we performed a two-sample Mendelian randomization analysis to investigate the causal link between inflammatory bowel disease and level of BMD using publically available GWAS summary statistics.Methods: A series of quality control steps were taken in our analysis to select eligible instrumental SNPs which were strongly associated with exposure. To make the conclusions more robust and reliable, we utilized several robust analytical methods (inverse-variance weighting, MR-PRESSO method, mode-based estimate method, weighted median, MR-Egger regression, and MR.RAPS method) that are based on different assumptions of two-sample MR analysis. The MR-Egger intercept test, Cochran’sQtest, and “leave-one-out” sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on BMD. Outlier variants identified by the MR-PRESSO outlier test were removed step-by-step to reduce heterogeneity and the effect of horizontal pleiotropy.Results: Our two-sample Mendelian randomization analysis with two groups of exposure GWAS summary statistics and four groups of outcome GWAS summary statistics suggested a definitively causal effect of genetically predicted ulcerative colitis on TB-BMD and FA-BMD but not on FN-BMD or LS-BMD (after Bonferroni correction), and we merely determined a causal effect of Crohn’s disease on FN-BMD but not on the others, which was somewhat inconsistent with many published observational researches. The causal effect of inflammatory bowel disease on TB-BMD was significant and robust but not on FA-BMD, FN-BMD, and LS-BMD, which might result from the cumulative effect of ulcerative colitis and Crohn’s disease on BMDs.Conclusions: Our Mendelian randomization analysis supported the causal effect of ulcerative colitis on TB-BMD and FA-BMD. As to Crohn’s disease, only the definitively causal effect of it on decreased FN-BMD was observed. Updated MR analysis is warranted to confirm our findings when a more advanced method to get less biased estimates and better precision or GWAS summary data with more ulcerative colitis and Crohn’s disease patients was available.

Intervertebral disc degeneration (IDD) is the primary pathological mechanism that underlies low back pain. Overloading-induced cell death, especially endogenous stem cell death, is the leading factor that undermines intrinsic repair and aggravates IDD. Previous research has separately studied the effect of oxygen concentration and mechanical loading in IDD. However, how these two factors synergistically influence endogenous repair remains unclear. Therefore, we established in vitro and in vivo models to study the mechanisms by which hypoxia interacted with overloading-induced cell death of the nucleus pulposus derived stem cells (NPSCs). We found the content of HIF1A (hypoxia inducible factor 1 subunit alpha) and the number of NPSCs decreased with disc degeneration in both rats and human discs. Hence, we isolated this subpopulation from rat discs and treated them simultaneously with hypoxia and excessive mechanical stress. Our results demonstrated that hypoxia exerted protective effect on NPSCs under compression, partially through elevating macroautophagy/autophagy. Proteomics and knockdown experiments further revealed HIF1A-BNIP3-ATG7 axis mediated the increase in autophagy flux, in which HMOX1 and SLC2A1 were also involved. Moreover, HIF1A-overexpressing NPSCs exhibited stronger resistance to over-loading induced apoptosis in vitro. They also showed higher survival rates, along with elevated autophagy after being intra-disc transplanted into over-loaded discs. Jointly, both in vivo and in vitro experiments proved the anti-apoptotic effect of HIF1A on NPSCs under the excessive mechanical loading, suggesting that restoring hypoxia and manipulating autophagy is crucial to maintain the intrinsic repair and to retard disc degeneration. Abbreviations: 3-MA: 3-methyladenine; ACAN: aggrecan; ATG7: autophagy related 7; BafA1: bafilomycin A₁; BAX: BCL2 associated X, apoptosis regulator; BECN1: beclin 1; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; CASP3: caspase 3; CCK8: cell counting kit-8; CHT: chetomin; CMP: compression; CoCl₂: cobalt chloride; COL2A1: collagen type II alpha 1 chain; Ctrl: control; DAPI: 4,6-diamidino-2-phenylindole; DEP: differentially expressed protein; DiR: 1,1-dioctadecyl-3,3,3,3-tetramethyl indotricarbocyanine; ECM: extracellular matrix; FCM: flow cytometry; GD2: disialoganglioside GD 2; GFP: green fluorescent protein; GO: gene ontology; GSEA: gene set enrichment analysis; H&E: hematoxylin-eosin; HIF1A: hypoxia inducible factor 1 subunit alpha; HK2: hexokinase 2; HMOX1: heme oxygenase 1; HX: hypoxia mimicry; IDD: intervertebral disc degeneration; IF: immunofluorescence; IHC: immunohistochemistry; IVD: intervertebral disc; KEGG: kyoto encyclopedia of genes and genomes; LBP: low back pain; Lv: lentivirus; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MMP: mitochondrial membrane potential; NC: negative control; NIR: near-infrared; NP: nucleus pulposus; NPC: nucleus pulposus cell; NPSC: nucleus pulposus derived stem cell; NX: normoxia; PPI: protein-protein interactions; RFP: red fluorescent protein; SLC2A1/GLUT1: solute carrier family 2 member 1; SQSTM1/p62: sequestosome 1; TEK/TIE2: TEK receptor tyrosine kinase; TEM: transmission electron microscopy; TUBB: tubulin beta class I.

Aging is a natural process, which plays a critical role in the pathogenesis of a variety of diseases, i.e., aging-related diseases, such as diabetes, osteoarthritis, Alzheimer disease, cardiovascular diseases, cancers, obesity and other metabolic abnormalities. Metformin, the most widely used antidiabetic drug, has been reported to delay aging and display protective effect on attenuating progression of various aging-related diseases by impacting key hallmark events of aging, including dysregulated nutrient sensing, loss of proteostasis, mitochondrial dysfunction, altered intercellular communication, telomere attrition, genomic instability, epigenetic alterations, stem cell exhaustion and cellular senescence. In this review, we provide updated information and knowledge on applications of metformin in prevention and treatment of aging and aging-related diseases. We focus our discussions on the roles and underlying mechanisms of metformin in modulating aging and treating aging-related diseases.