Emerging role of liver-bone axis in osteoporosis.

Background: Increasing attention to liver-bone crosstalk has spurred interest in targeted interventions for various forms of osteoporosis. Liver injury induced by different liver diseases can cause an imbalance in bone metabolism, indicating a novel regulatory paradigm between the liver and bone. However, the role of the liver-bone axis in both primary and secondary osteoporosis remains inadequately elucidated. Therefore, exploring the exact regulatory mechanisms of the liver-bone axis may offer innovative clinical approaches for treating diseases associated with the liver and bone. Methods: Here, we summarize the latest research on the liver-bone axis by searching the PubMed and Web of Science databases and discuss the possible mechanism of the liver-bone axis in different types of osteoporosis. The literature directly reporting the regulatory role of the liver-bone axis in different types of osteoporosis from the PubMed and Web of Science databases has been included in the discussion of this review (including but not limited to the definition of the liver-bone axis, clinical studies, and basic research). In addition, articles discussing changes in bone metabolism caused by different etiologies of liver injury have also been included in the discussion of this review (including but not limited to clinical studies and basic research). Results: Several endocrine factors (IGF-1, FGF21, hepcidin, vitamin D, osteocalcin, OPN, LCAT, Fetuin-A, PGs, BMP2/9, IL-1/6/17, and TNF-α) and key genes (SIRT2, ABCB4, ALDH2, TFR2, SPTBN1, ZNF687 and SREBP2) might be involved in the regulation of the liver-bone axis. In addition to the classic metabolic pathways involved in inflammation and oxidative stress, iron metabolism, cholesterol metabolism, lipid metabolism and immunometabolism mediated by the liver-bone axis require more research to elucidate the regulatory mechanisms involved in osteoporosis. Conclusion: During primary and secondary osteoporosis, the liver-bone axis is responsible for liver and bone homeostasis via several hepatokines and osteokines as well as biochemical signaling. Combining multiomics technology and data mining technology could further advance our understanding of the liver-bone axis, providing new clinical strategies for managing liver and bone-related diseases.The translational potential of this article is as follows: Abnormal metabolism in the liver could seriously affect the metabolic imbalance of bone. This review summarizes the indispensable role of several endocrine factors and biochemical signaling pathways involved in the liver-bone axis and emphasizes the important role of liver metabolic homeostasis in the pathogenesis of osteoporosis, which provides novel potential directions for the prevention, diagnosis, and treatment of liver and bone-related diseases.

Multi-Sensing Inspection System for Thermally Induced Micro-Instability in Metal-Based Selective Laser Melting.

Additive manufacturing (AM) excels in engineering intricate shapes, pioneering functional components, and lightweight structures. Nevertheless, components fabricated through AM often manifest elevated residual stresses and a myriad of thermally induced micro-instabilities, including cracking, incomplete fusion, crazing, porosity, spheroidization, and inclusions. In response, this study proposed a sophisticated multi-sensing inspection system specifically tailored for the inspection of thermally induced micro-instabilities at the micro-nano scale. Simulation results substantiate that the modulation transfer function (MTF) values for each field of view in both visible and infrared optical channels surpass the benchmark of 0.3, ensuring imaging fidelity conducive to meticulous examination. Furthermore, the innovative system can discern and accurately capture data pertaining to thermally induced micro-instabilities across visible and infrared spectra, seamlessly integrating this information into a backend image processing system within operational parameters of a 380-450 mm distance and a 20-70 °C temperature range. Notably, the system's design is harmoniously aligned with the requisites of processing and assembly, heralding a significant advancement in bolstering the inspection effect of thermally induced micro-instabilities for the AM component.

Comparative analysis of noise and music exposure on inflammatory responses on lipopolysaccharide-induced septic rats.

OBJECTIVE: Environmental factors such as noise and music can significantly impact physiological responses, including inflammation. This study explored how environmental factors like noise and music affect lipopolysaccharide (LPS)-induced inflammation, with a focus on systemic and organ-specific responses. MATERIALS AND METHODS: 24 Wistar rats were divided into four groups (n = 6 per group): Control group, LPS group, noise-exposed group, and music-exposed group. All rats, except for the Control group, received 10 mg/kg LPS intraperitoneally. The rats in the noise-exposed group were exposed to 95 dB noise, and the music-exposed group listened to Mozart's K. 448 music (65-75 dB) for 1 h daily over 7 days. An enzyme-linked immunosorbent assay was utilized to detect the levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), in serum and tissues (lung, liver, and kidney). Western blot examined the phosphorylation levels of nuclear factor-κB (NF-κB) p65 in organ tissues. RESULTS: Compared with the Control group, LPS-induced sepsis rats displayed a significant increase in the levels of TNF-α and IL-1ß in serum, lung, liver, and kidney tissues, as well as a remarkable elevation in the p-NF-κB p65 protein expression in lung, liver, and kidney tissues. Noise exposure further amplified these inflammatory markers, while music exposure reduced them in LPS-induced sepsis rats. CONCLUSION: Noise exposure exacerbates inflammation by activating the NF-κB pathway, leading to the up-regulation of inflammatory markers during sepsis. On the contrary, music exposure inhibits NF-κB signaling, indicating a potential therapeutic effect in reducing inflammation.

Discovery of Novel Neo-Clerodane Derivatives as Potent Dual-Functional Antiosteoporosis Agents through Targeting Peroxisome Proliferator-Activated Receptor-γ.

A library of 31 natural neo-clerodanes isolated from Ajuga decumbens was assayed for antiosteoporosis. This results in 18 neo-clerodane osteoclastogenesis inhibitors, and compound 3 prevents bone loss in vivo. Further mechanistic studies demonstrated that these compounds inhibit osteoporosis by antagonizing peroxisome proliferator-activated receptor-γ (PPARγ). We designed and synthesized 17 compounds by chemically modifying the natural neo-clerodane 19 (highly potent and the major composition of A. decumbens extract) by means of structure-based drug design techniques. Among these neo-clerodane derivatives, compound 34 is the most potent osteoporosis inhibitor with a 46-fold improvement in inhibiting osteoclastogenesis (IC50 = 0.042 vs 1.92 µM), 11-fold increased activity in PPARγ antagonism (EC50 = 0.75 vs 8.35 µM), 66-fold enhancement in receptor affinity (KD = 0.27 vs 17.7 µM), and enhanced osteogenic promotion compared to 19. This underscores the potential of neo-clerodane diterpenoids as promising leads for osteoporosis treatment by targeting PPARγ.

Identification of differentially expressed genes, pathways, and immune infiltration in diabetes.

This study aimed to perform exhaustive bioinformatic analysis by using GSE29221 micro-array maps obtained from healthy controls and Type 2 Diabetes (T2DM) patients. Raw data are downloaded from the Gene Expression Omnibus database and processed by the limma package in R software to identify Differentially Expressed Genes (DEGs). Gene ontology functional analysis and Kyoto Gene Encyclopedia and Genome Pathway analysis are performed to determine the biological functions and pathways of DEGs. A protein interaction network is constructed using the STRING database and Cytoscape software to identify key genes. Finally, immune infiltration analysis is performed using the Cibersort method. This study has implications for understanding the underlying molecular mechanism of T2DM and provides potential targets for further research.

Four new phenolic constituents from root barks of Paeonia ostii.

The Paeonia ostii, also known as "Feng Dan" have a crucial role in folk medicine to treat lumbar muscles strain, knee osteoarthritis and cervical spondylosis. In this study, four new phenolic compounds, specifically Paeoniaostiph A-E (1-4) phenolic compounds were characterised through spectroscopic techniques, including 1D and 2D NMR, HRESIMS, UV, IR, and electronic circular dichroism computations to explore their structures. Cytotoxicity and NO production inhibition of the new phenolic compounds were also studied. The results of the cytotoxicity experiment showed that compound 1 is cytotoxic to two human cancer cell lines with IC50 values ranging from 13.3 to 13.5 µM. Compounds 1 and 2 showed certain inhibitory activity on NO production. This is the first report on isolating the components from natural sources.

Design of novel triply periodic minimal surface (TPMS) bone scaffold with multi-functional pores: lower stress shielding and higher mass transport capacity.

Background: The bone repair requires the bone scaffolds to meet various mechanical and biological requirements, which makes the design of bone scaffolds a challenging problem. Novel triply periodic minimal surface (TPMS)-based bone scaffolds were designed in this study to improve the mechanical and biological performances simultaneously. Methods: The novel bone scaffolds were designed by adding optimization-guided multi-functional pores to the original scaffolds, and finite element (FE) method was used to evaluate the performances of the novel scaffolds. In addition, the novel scaffolds were fabricated by additive manufacturing (AM) and mechanical experiments were performed to evaluate the performances. Results: The FE results demonstrated the improvement in performance: the elastic modulus reduced from 5.01 GPa (original scaffold) to 2.30 GPa (novel designed scaffold), resulting in lower stress shielding; the permeability increased from 8.58 × 10-9 m2 (original scaffold) to 5.14 × 10-8 m2 (novel designed scaffold), resulting in higher mass transport capacity. Conclusion: In summary, the novel TPMS scaffolds with multi-functional pores simultaneously improve the mechanical and biological performances, making them ideal candidates for bone repair. Furthermore, the novel scaffolds expanded the design domain of TPMS-based bone scaffolds, providing a promising new method for the design of high-performance bone scaffolds.

In Situ Growth Method for Large-Area Flexible Perovskite Nanocrystal Films.

Metal halide perovskites have shown unique advantages compared with traditional optoelectronic materials. Currently, perovskite films are commonly produced by either multi-step spin coating or vapor deposition techniques. However, both methods face challenges regarding large-scale production. Herein, we propose a straightforward in situ growth method for the fabrication of CsPbBr3 nanocrystal films. The films cover an area over 5.5 cm × 5.5 cm, with precise thickness control of a few microns and decent uniformity. Moreover, we demonstrate that the incorporation of magnesium ions into the perovskite enhances crystallization and effectively passivates surface defects, thereby further enhancing luminous efficiency. By integrating this approach with a silicon photodiode detector, we observe an increase in responsivity from 1.68 × 10-2 A/W to 3.72 × 10-2 A/W at a 365 nm ultraviolet wavelength.

Atomic Depth Image Transfer of Large-Area Optical Quartz Materials Based on Pulsed Ion Beam.

The high-efficiency preparation of large-area microstructures of optical materials and precision graphic etching technology is one of the most important application directions in the atomic and near-atomic-scale manufacturing industry. Traditional focused ion beam (FIB) and reactive ion etching (RIE) methods have limitations in precision and efficiency, hindering their application in automated mass production. The pulsed ion beam (PIB) method addresses these issues by enhancing ion beam deflection to achieve high-resolution material removal on a macro scale, which can reach the equivalent removal resolution of 6.4 × 10-4 nm. Experiments were conducted on a quartz sample (10 × 10 × 1 mm) with a specific pattern mask using the custom PIB processing device. The surface morphology, etching depth, and roughness were measured post-process. The results demonstrated that precise control over cumulative sputtering time yielded well-defined patterns with expected average etching depths and surface roughness. This confirms the PIB technique's potential for precise atomic depth image transfer and its suitability for industrial automation, offering a significant advancement in microfabrication technology.

New alkylamides from the pericarps of Zanthoxylum schinifolium.

The pericarps of Zanthoxylum schinifolium Sieb. et Zucc were called "green huajiao", which were used as traditional folk medicine and popular seasoning in China. In this study, twenty-seven alkylamides, including a rare alkylamide containing two amide groups (1), an alkylamide with a furan ring (5), six new alkylamide analogues (2-4, 6-8), together with nineteen known alkylamides (9-27) were isolated from green huajiao. Their structures were elucidated by extensive spectroscopic analysis, including 1D, 2D NMR, HRESIMS, and UV spectra. Furthermore, compounds 5, 18, 21, and 22 exhibited weak protective activity for corticosterone-induced PC12 cells damage.

Inhibition of HDAC activity directly reprograms murine embryonic stem cells to trophoblast stem cells.

Embryonic stem cells (ESCs) can differentiate into all cell types of the embryonic germ layers. ESCs can also generate totipotent 2C-like cells and trophectodermal cells. However, these latter transitions occur at low frequency due to epigenetic barriers, the nature of which is not fully understood. Here, we show that treating mouse ESCs with sodium butyrate (NaB) increases the population of 2C-like cells and enables direct reprogramming of ESCs into trophoblast stem cells (TSCs) without a transition through a 2C-like state. Mechanistically, NaB inhibits histone deacetylase activities in the LSD1-HDAC1/2 corepressor complex. This increases acetylation levels in the regulatory regions of both 2C- and TSC-specific genes, promoting their expression. In addition, NaB-treated cells acquire the capacity to generate blastocyst-like structures that can develop beyond the implantation stage in vitro and form deciduae in vivo. These results identify how epigenetics restrict the totipotent and trophectoderm fate in mouse ESCs.

Research progress on GPX4 targeted compounds.

Blocking the System Xc-_ GSH_GPX4 pathway to induce ferroptosis in tumor cells is a novel strategy for cancer treatment. GPX4 serves as the core of the System Xc-/GSH/GPX4 pathway and is a predominant target for inducing ferroptosis in tumor cells. This article summarizes compounds identified in current research that directly target the GPX4 protein, including inhibitors, activators, small molecule degraders, chimeric degraders, and the application of combination therapies with other drugs, aiming to promote further research on the target and related diseases.

Dihydroartemisinin-driven TOM70 inhibition leads to mitochondrial destabilization to induce pyroptosis against lung cancer.

Enhancement of malignant cell immunogenicity to relieve immunosuppression of lung cancer microenvironment is essential in lung cancer treatment. In previous study, we have demonstrated that dihydroartemisinin (DHA), a kind of phytopharmaceutical, is effective in inhibiting lung cancer cells and boosting their immunogenicity, while the initial target of DHA's intracellular action is poorly understood. The present in-depth analysis aims to reveal the influence of DHA on the highly expressed TOM70 in the mitochondrial membrane of lung cancer. The affinity of DHA and TOM70 was analyzed by microscale thermophoresis (MST), pronase stability, and thermal stability. The functions and underlying mechanism were investigated using western blots, qRT-PCR, flow cytometry, and rescue experiments. TOM70 inhibition resulted in mtDNA damage and translocation to the cytoplasm from mitochondria due to the disruption of mitochondrial homeostasis. Further ex and in vivo findings also showed that the cGAS/STING/NLRP3 signaling pathway was activated by mtDNA and thereby malignant cells underwent pyroptosis, leading to enhanced immunogenicity of lung cancer cells in the presence of DHA. Nevertheless, DHA-induced mtDNA translocation and cGAS/STING/NLRP3 mobilization were synchronously attenuated when TOM70 was replenished. Finally, DHA was demonstrated to possess potent anti-lung cancer efficacy in vitro and in vivo. Taken together, these data confirm that TOM70 is an important target for DHA to disturb mitochondria homeostasis, which further activates STING and arouses pyroptosis to strengthen immunogenicity against lung cancer thereupon. The present study provides vital clues for phytomedicine-mediated anti-tumor therapy.

Dihydroartemisinin-driven selective anti-lung cancer proliferation by binding to EGFR and inhibition of NRAS signaling pathway-induced DNA damage.

Chemotherapeutic agents can inhibit the proliferation of malignant cells due to their cytotoxicity, which is limited by collateral damage. Dihydroartemisinin (DHA), has a selective anti-cancer effect, whose target and mechanism remain uncovered. The present work aims to examine the selective inhibitory effect of DHA as well as the mechanisms involved. The findings revealed that the Lewis cell line (LLC) and A549 cell line (A549) had an extremely rapid proliferation rate compared with the 16HBE cell line (16HBE). LLC and A549 showed an increased expression of NRAS compared with 16HBE. Interestingly, DHA was found to inhibit the proliferation and facilitate the apoptosis of LLC and A549 with significant anti-cancer efficacy and down-regulation of NRAS. Results from molecular docking and cellular thermal shift assay revealed that DHA could bind to epidermal growth factor receptor (EGFR) molecules, attenuating the EGF binding and thus driving the suppressive effect. LLC and A549 also exhibited obvious DNA damage in response to DHA. Further results demonstrated that over-expression of NRAS abated DHA-induced blockage of NRAS. Moreover, not only the DNA damage was impaired, but the proliferation of lung cancer cells was also revitalized while NRAS was over-expression. Taken together, DHA could induce selective anti-lung cancer efficacy through binding to EGFR and thereby abolishing the NRAS signaling pathway, thus leading to DNA damage, which provides a novel theoretical basis for phytomedicine molecular therapy of malignant tumors.

Evaluation of a new real-time source apportionment system of PM2.5 and its implication on rapid aging of vehicle exhaust.

Accurate identification and rapid analysis of PM2.5 sources and formation mechanisms are essential to mitigate PM2.5 pollution. However, studies were limited in developing a method to apportion sources to the total PM2.5 mass in real-time. In this study, we developed a real-time source apportionment method based on chemical mass balance (CMB) modeling and a mass-closure PM2.5 composition online monitoring system in Shenzhen, China. Results showed that secondary sulfate, secondary organic aerosol (SOA), vehicle emissions and secondary nitrate were the four major PM2.5 sources during autumn 2019 in Shenzhen, together contributed 76 % of PM2.5 mass. The novel method was verified by comparing with other source apportionment methods, including offline filter analysis, aerosol mass spectrometry, and carbon isotopic analysis. The comparison of these methods showed that the new real-time method obtained results generally consistent with the others, and the differences were interpretable and implicative. SOA and vehicle emissions were the major PM2.5 and OA contributors by all methods. Further investigation on the OA sources indicated that vehicle emissions were not only the main source of primary organic aerosol (POA), but also the main contributor to SOA by rapid aging of the exhaust in the atmosphere. Our results demonstrated the great potential of the new real-time source apportionment method for aerosol pollution control and deep understandings on emission sources.

Tea saponin co-ball milled commercial micro zero-valent iron for boosting Cr(VI) removal.

Tea saponins (TS), a natural biosurfactant extracted from tea trees, were co-ball milled with commercial micro zero-valent iron (mZVI) to produce TS modified mZVI (TS-BZVI) for efficient hexavalent chromium (Cr(VI)) removal. The findings demonstrated that TS-BZVI could nearly remove 100% of Cr(VI) within 2 h, which was 1.43 times higher than that by ball milled mZVI (BZVI) (70%). Kinetics analysis demonstrated a high degree of compatibility with the pseudo-second-order (PSO), revealing that TS-BZVI exhibited a 2.83 times faster Cr(VI) removal rate involved primarily chemisorption. Further, X-ray photoelectron spectroscopy (XPS) and X-ray absorption near edge structure (XANES) measurements indicated that the TS co-ball milling process improved the exposure of Fe(II) and Fe(0) on mZVI, which further promoted the Cr(VI) reduction process. Impressively, the introduction of TS increased the hydrophobicity of ZVI, effectively inhibiting the H2 evolution by 95%, thus improved electron selectivity for efficient Cr(VI) removal. Ultimately, after operating for 10 days, a simulated permeable reactive barrier (PRB) column experiment revealed that TS-BZVI had a higher Cr(VI) elimination efficiency than BZVI, indicating that TS-BZVI was promising for practical environment remediation.

A Mendelian randomization study to examine the causal associations of circulating micronutrient levels with frailty risk.

Background: Observational studies have shown that micronutrients can affect the occurrence of frailty. However, it is not clear whether there is a causal relationship between the two. This study aimed to explore the causal relationship between circulating micronutrient levels and frailty risk using a two-sample Mendelian randomization (TSMR) approach. Methods: We gathered and screened instrumental variables (IVs) for six circulating micronutrients, including vitamin B12, vitamin B6, folate, vitamin C, vitamin D, and vitamin E, from published genome-wide association studies (GWAS) and the IEU OpenGWAS open database. Summary statistics for frailty were obtained from a GWAS meta-analysis, including the UK Biobank and TwinGene (N = 175,226). We performed two independent TSMR analyses and a meta-analysis based on the two independent MR estimates to assess the causal relationship between circulating micronutrientn and frailty. Results: Our study found, no causal relationship between genetically predicted vitamin D (ß = -0.059, p = 0.35), vitamin B6 (ß = 0.006, p = 0.80), vitamin E (ß = -0.011, p = 0.79), vitamin C (ß = -0.044, p = 0.06), vitamin B12 (ß = -0.027, p = 0.37), and folate (ß = 0.029, p = 0.17), with frailty. Conclusion: This study showed that these six micronutrients did not reduce the risk of developing frailty. However, we think it is necessary further to investigate the relationship and mechanisms between micronutrients and frailty using methods such as randomized controlled trials.

B-Myb deficiency boosts bortezomib-induced immunogenic cell death in colorectal cancer.

B-Myb has received considerable attention for its critical tumorigenic function of supporting DNA repair. However, its modulatory effects on chemotherapy and immunotherapy have rarely been reported in colorectal cancer. Bortezomib (BTZ) is a novel compound with chemotherapeutic and immunotherapeutic effects, but it fails to work in colorectal cancer with high B-Myb expression. The present study was designed to investigate whether B-Myb deletion in colorectal cancer could potentiate the immune efficacy of BTZ against colorectal cancer and to clarify the underlying mechanism. Stable B-Myb knockdown was induced in colorectal cancer cells, which increased apoptosis of the cancer cells relative to the control group in vitro and in vivo. We found that BTZ exhibited more favourable efficacy in B-Myb-defective colorectal cancer cells and tumor-bearing mice. BTZ treatment led to differential expression of genes enriched in the p53 signaling pathway promoted more powerful downstream DNA damage, and arrested cell cycle in B-Myb-defective colorectal cancer. In contrast, recovery of B-Myb in B-Myb-defective colorectal cancer cells abated BTZ-related DNA damage, cell cycle arrest, and anticancer efficacy. Moreover, BTZ promoted DNA damage-associated enhancement of immunogenicity, as indicated by potentiated expression of HMGB1 and HSP90 in B-Myb-defective cells, thereby driving M1 polarization of macrophages. Collectively, B-Myb deletion in colorectal cancer facilitates the immunogenic death of cancer cells, thereby further promoting the immune efficacy of BTZ by amplifying DNA damage. The present work provides an effective molecular target for colorectal cancer immunotherapy with BTZ.

The structures of two polysaccharides from Lepidium meyenii and their immunomodulatory effects via activating NF-κB signaling pathway.

Lepidium meyenii Walp., also known as the "Peruvian national treasure", is a popular functional food in the daily lives of Peruvian people due to its bioactive with main polysaccharides. However, studies on polysaccharides isolated from Lepidium meyenii were few. Two new highly heterogeneous polysaccharides, MCP-1a and MCP-2b, were isolated and purified from the tuber of Lepidium meyenii. The structure characterization revealed that MCP-1a primarily consisted of D-Glc and had a molecular weight of 6.6 kDa. Its backbone was composed of 1,4,6-α-D-Glc, while branches feature T-α-L-Ara, 1,5-α-L-Ara, and T-α-D-Glc attached to the O-6 positions. MCP-2b was a rare arabinogalactan with a molecular weight of 49.4 kDa. Interestingly, the backbone of MCP-2b was composed of 1,6-ß-D-Gal, 1,3,6-ß-D-Gal with a few 1,3-ß-D-GlcpA-4-OMe units inserted. Side chains of MCP-2b were mainly composed of 1,3-ß-D-Gal, T-ß-D-Gal, T-α-L-Ara, 1,5-α-L-Ara, with trace amounts of 1,4-ß-D-Glc and T-ß-D-Glc. The bioactivity assay results revealed that MCP-1a and MCP-2b increased the release of NO, IL-1ß, TNF-α, and IL-6 from RAW 264.7 cells at concentrations ranging from 50 µg/mL to 400 µg/mL. Furthermore, MCP-1a and MCP-2b could promote the expression of key transcription factors (IκB-α, p-IκB-α, p65, and p-p65) in the NF-κB pathway, indicating that MCP-1a and MCP-2b had potential immunomodulatory activities.

Control of chlorination disinfection by-products in drinking water by combined nanofiltration process: A case study with trihalomethanes and haloacetic acids.

Disinfection by-products (DBPs) are prevalent contaminants in drinking water and are primarily linked to issues regarding water quality. These contaminants have been associated with various adverse health effects. Among different treatment processes, nanofiltration (NF) has demonstrated superior performance in effectively reducing the levels of DBPs compared to conventional processes and ozone-biological activated carbon (O3-BAC) processes. In this experiment, we systematically investigated the performance of three advanced membrane filtration treatment schemes, namely "sand filter + nanofiltration" (SF + NF), "sand filter + ozone-biological activated carbon + nanofiltration" (SF + O3-BAC + NF), and "ultrafiltration + nanofiltration" (UF + NF), in terms of their ability to control disinfection by-product (DBP) formation in treated water, analyzed the source and fate of DBP precursors during chlorination, and elucidated the role of precursor molecular weight distribution during membrane filtration in relation to DBP formation potential (DBPFP). The results indicated that each treatment process reduced DBPFP, as measured by trihalomethane formation potential (THMFP) and haloacetic acid formation potential (HAAFP), with the SF + O3-BAC + NF process being the most effective (14.27 µg/L and 14.88 µg/L), followed by the SF + NF process (21.04 µg/L and 16.29 µg/L) and the UF + NF process (26.26 µg/L and 21.75 µg/L). Tyrosine, tryptophan, and soluble microbial products were identified as the major DBP precursors during chlorination, with their fluorescence intensity decreasing gradually as water treatment progressed. Additionally, while large molecular weight organics (60-100,000 KDa) played a minor role in DBPFP, small molecular weight organics (0.2-5 KDa) were highlighted as key contributors to DBPFP, and medium molecular weight organics (5-60 KDa) could adhere to the membrane surface and reduce DBPFP. Based on these findings, the combined NF process can be reasonably selected for controlling DBP formation, with potential long-term benefits for human health.