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Bacterial infections present a major global health threat, often displaying resistance to various antibiotics. Lipoteichoic acid (LTA) is a vital component of bacterial cell envelopes of Gram-positive bacteria, crucial for cell integrity, cell division, and host inflammation. Due to its essential role for bacteria, LTA and its biosynthesis are also attractive drug targets, however, there is only scant molecular knowledge on LTA and its precursor molecules in membranes. Here, we report the isolation and molecular characterization of diglucosyldiacylglycerol (Glc2-DAG), the glycolipid precursor molecule that anchors LTA in the bacterial plasma-membrane. Using a tailored growth medium and purification protocols, we isolated 13C-isotope labelled Glc2-DAG from bacteria, which can then be used for high-resolution NMR studies. Using solution-state and solid-state NMR, we show an in-depth molecular characterization of Glc2-DAG, including in native-like membranes. Our approach may help to identify antibiotics that directly target LTA precursor molecules, and it offers a tool for future investigations into the role of Glc2-DAG in bacterial physiology.
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OBJECTIVE: To create a census-based composite neighborhood socioeconomic deprivation index (NSDI) from geocoded residential addresses and to quantify how NSDI aligns with individual-level socioeconomic factors among people with traumatic brain injury (TBI). SETTING: Community. PARTICIPANTS: People enrolled in the TBI Model Systems National Database (TBIMS NDB). DESIGN: Secondary analysis of a longitudinal cohort study. MAIN MEASURES: The TBIMS-NSDI was calculated at the census tract level for the United States population based on a principal components analysis of eight census tract-level variables from the American Community Survey. Individual socioeconomic characteristics from the TBIMS NDB were personal household income, education (years), and unemployment status. Neighborhood:Individual NSDI residuals represent the difference between predicted neighborhood disadvantage based on individual socioeconomic characteristics versus observed neighborhood disadvantage based on the TBIMS-NSDI. RESULTS: A single principal component was found to encompass the eight socioeconomic neighborhood-level variables. It was normally distributed across follow-up years 2, 5, and 10 post-injury in the TBIMS NDB. In all years, the TBIMS-NDSI was significantly associated with individual-level measures of household income and education but not unemployment status. Males, persons of Black and Hispanic background, Medicaid recipients, persons with TBI caused by violence, and those living in urban areas, as well as in the Northeast or Southern regions of the United States, were more likely to have greater neighborhood disadvantage than predicted based on their individual socioeconomic characteristics. CONCLUSIONS: The TBIMS-NSDI provides a neighborhood-level indicator of socioeconomic disadvantage, an important social determinant of outcomes from TBI. The Neighborhood:Individual NSDI residual adds another dimension to the TBIMS-NSDI by summarizing how a person's socioeconomic status aligns with their neighborhood socioeconomics. Future studies should evaluate how both measures affect TBI recovery and life quality. Research studying neighborhood socioeconomic disadvantage may improve our understanding of how systemic adversity influences outcomes after TBI.
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Epigenetic modifications influence gene expression and effects cancer initiation and progression. Therefore, they serve as diagnostic and prognostic biomarkers and potential therapeutic targets. Natural Killer (NK) cells, integral to the innate immune system, exhibit anti-tumor effect by recognizing and eliminating cancerous cells through the balance of activating and inhibitory ligands. Understanding the epigenetic regulation of NK cell ligands offers insights into enhancing NK cell-mediated tumor eradication. This review explores the epigenetic modifications governing the expression of activating NKG2D ligands and discusses clinical trials investigating NK cell-based immunotherapies, highlighting their potential as effective cancer treatment strategies. Case studies examining the safety and effectiveness of NK cell therapies in different cancer types, such as acute myeloid leukemia (AML) and non-small cell lung cancer (NSCLC), demonstrate promising outcomes with minimal toxicity. These findings underscore the therapeutic prospects of epigenetic modulation of NKG2D ligands and NK cell-based immunotherapies as effective cancer treatment strategies. Future research in the advancement of personalized medicine approaches and novel combination therapies with NK cell will further improve treatment outcomes and provide new therapeutic options for treating patients with various types of cancer.
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In our quest to find improved anticancer therapeutics, we expedite the lead optimization of (E)-1-((3,4,5-trimethoxybenzylidene)amino)-4-(3,4,5-trimethoxyphenyl)imidazo[1,2-a]quinoxaline-2-carbonitrile (6b), an EGFR inhibitor previously discovered in our laboratory through an in-house screening program. The lead optimization was rationally initiated considering the catalytic site of EGFR. We synthesized twenty-nine new analogues of 6b and assessed their anticancer activities. SAR studies highlighted the role of important groups in controlling anticancer activities. Among all, 5a and 5l were found to exhibit improved EGFR inhibition with anticancer asset potential. In silico studies corroborated with in vitro EGFR inhibitory results. The deeper analysis of 5a and 5l revealed that these synthetics could alter the MMP (ΔΨ m) and significantly reduce the ROS levels in lung cancer cells. This is a vital prerequisite for better plausible EGFR inhibitors devoid of cardiotoxicity. qPCR analysis further revealed that the investigational compounds 5a and 5l were able to downregulate the expression of key oncogenes, viz., KRAS, MAP2K, and EGFR. The downregulation of these genes suggests that the investigational compounds could interact and inhibit key players in the signalling cascade along with the EGFR, which may lead to the inhibition of the growth and prognosis of cancer cells via a holistic approach.
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Malignant phyllodes, along with ductal carcinoma, is known as metaplastic cancer of the breast. This tumor is additionally known as breast carcinosarcoma. Malignant phyllodes in conjunction with ductal carcinoma is a rare finding in routine clinical practice. We describe the case report of a 47-year-old female patient who arrived with a large right breast mass. A core biopsy was performed, and histopathological examination indicated that the tumor was a malignant phyllodes tumor. A positron emission tomography (PET) scan revealed hyper-metabolic and hypo-metabolic tumors with perilesional stranding and satellite nodularity. There were a few metastatic right axillary nodes visible. There was no indication of distant metastases. Due to the presence of both components, a modified radical mastectomy surgery with axillary dissection was undertaken for this patient. Histopathological analysis of paraffin sections revealed ductal carcinoma in situ (DCIS) comedo-epithelial component and spindle-shaped cells with hyper-chromatic oval nuclei and scanty cytoplasm.
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[This corrects the article DOI: 10.1016/j.dialog.2023.100129.].
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High-altitude (HA) environment presents immense physiological adversities for humans that have been overcome by supplementing bio-active phytochemicals from functional foods that support and accelerate acclimatization under these extreme environmental conditions. Several agricultural interventions have been investigated to enhance the phytochemical content in vegetables however; these studies have been limited to low-altitude (LA) regions only. In view of an existing knowledge gap, current work is designed to compare the phytochemical compositions of HA and LA-grown Brassicaceae vegetables (cabbage, cauliflower, knol-khol, and radish) using organic treatments via farm yard manure (FYM) and Azotobacter. The open field study was conducted as a two-factorial randomized block design. The first factor was treatment (T1-FYM, T2-Azotobacter, T3-FYM + Azotobacter, and T4-control) while the second was locations (HA and LA). Among all these treatments, the application of treatment T3 in HA-grown cabbage showed the highest total phenolic content (TPC; 9.56 µg/mg), total flavonoids content (TFC; 14.48 µg/mg), and antioxidant potential using 2,2-diphenyl-1-picrylhydrazyl (DPPH; 85.97%) and ferric reducing antioxidant power (FRAP; 30.77 µg/mg) compared to LA grown samples. Reverse Phase high performance liquid chromatography (RP-HPLC) analysis showed that treatment T3 at HA led to significantly high kaempferol (0.92 µg/mg) and sulforaphane (8.94 µg/mg) contents in cabbage whereas, indole-3-carbinol (1.31 µg/mg) was higher in HA grown cauliflower. The present study provides scientific evidence for the enrichment of health-promoting phytochemical compounds in Brassicaceae vegetables grown with T3 treatment specifically at HA.
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Altitud , Brassicaceae , Fitoquímicos , Verduras , Brassicaceae/química , Verduras/química , Fitoquímicos/análisis , Antioxidantes/análisis , Fenoles/análisis , Frío , HumanosRESUMEN
OBJECTIVES: To identify personal, clinical, and environmental factors associated with 4 previously identified distinct multidimensional participation profiles of individuals following traumatic brain injury (TBI). SETTING: Community. PARTICIPANTS: Participants (n = 408) enrolled in the TBI Model Systems (TBIMS) Participation Module, all 1 year or more postinjury. DESIGN: Secondary data analysis of cross-sectional data from participants in a multicenter TBIMS module study on participation conducted between May 2006 and September 2007. Participants provided responses to questionnaires via a telephone interview at their study follow-up (1, 2, 5, 10, or 15 years postinjury). MAIN MEASURES: Participants provided responses to personal (eg, demographic), clinical (eg, function), environmental (eg, neighborhood type), and participation measures to create multidimensional participation profiles. Data from measures collected at the time of injury (preinjury questionnaire, injury characteristics) were also included. The primary outcome was assignment to one of 4 multidimensional participation profile groups based on participation frequency, importance, satisfaction, and enfranchisement. The measures used to develop the profiles were: Participation Assessment with Recombined Tools-Objective, Importance, and Satisfaction scores, each across 3 domains (Productivity, Social Relationships, Out and About in the Community) and the Enfranchisement Scale (contributing to one's community, feeling valued by the community, choice and control). RESULTS: Results of the multinomial regression analysis, with 4 distinct participation profile groups as the outcome, indicated that education, current employment, current illicit drug use, current driving status, community type, and Functional Independence Measure Cognitive at follow-up significantly distinguished participation profile groups. Findings suggest a trend toward differences in participation profile groups by race/Hispanic ethnicity. CONCLUSIONS: Understanding personal, clinical, and environmental factors associated with distinct participation outcome profiles following TBI may provide more personalized and nuanced guidance to inform rehabilitation intervention planning and/or ongoing clinical monitoring.
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Measurement of anisotropy factor (g) in the presence of nanoparticles (NPs) is important for understanding light distribution for plasmonic photothermal cancer therapeutics. Here, anisotropy factor is investigated through bilayer phantoms (epidermal and dermal) of various thicknesses incorporated with gold nanorods (GNRs) concentrations of 10-40 µg/mL by using in-house developed goniometric setup. Results show that 10 µg/mL GNRs in the phantom increase g by ~50% (g = 0.9471) w.r.t. phantom without NPs. Higher concentrations (40 µg/mL) of GNRs decrease g by ~43% (g = 0.5341) w.r.t. phantom with 10 µg/mL GNRs. For 40 µg/mL GNRs phantom, the anisotropy factor reduces by 47% for phantom thickness from 600 to 1800 µm. Anisotropy factor of GNR embedded phantom increased by 44% by using glycerol (10%-40%). Incorporation of NPs in a tumor significantly affects g, a major parameter for light distribution. These measurements provide insights for light scattering based on nanoparticle doses for plasmonic photothermal therapeutics.
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Oro , Neoplasias , Fantasmas de Imagen , Anisotropía , Oro/química , Neoplasias/terapia , Neoplasias/diagnóstico por imagen , Terapia Fototérmica , Nanotubos/química , Nanopartículas del Metal/química , HumanosRESUMEN
The increasing prevalence of bone replacements and complications associated with bone replacement procedures underscores the need for innovative tissue restoration approaches. Existing synthetic grafts cannot fully replicate bone vascularization and mechanical characteristics. This study introduces a novel strategy utilizing pectin, chitosan, and polyvinyl alcohol to create interpenetrating polymeric network (IPN) scaffolds incorporated with extracellular vesicles (EVs) isolated from human mesenchymal stem cells (hMSCs). We assess the osteointegration and osteoconduction abilities of these modelsin vitrousing hMSCs and MG-63 osteosarcoma cells. Additionally, we confirm exosome properties through Transmission Electron Microscopy (TEM), immunoblotting, and Dynamic Light Scattering (DLS).In vivo, chick allantoic membrane assay investigates vascularization characteristics. The study did not includein vivoanimal experiments. Our results demonstrate that the IPN scaffold is highly porous and interconnected, potentially suitable for bone implants. EVs, approximately 100 nm in size, enhance cell survival, proliferation, alkaline phosphatase activity, and the expression of osteogenic genes. EVs-mediated IPN scaffolds demonstrate promise as precise drug carriers, enabling customized treatments for bone-related conditions and regeneration efforts. Therefore, the EVs-mediated IPN scaffolds demonstrate promise as precise carriers for the transport of drugs, allowing for customized treatments for conditions connected to bone and efforts in regeneration.
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Regeneración Ósea , Proliferación Celular , Vesículas Extracelulares , Células Madre Mesenquimatosas , Osteogénesis , Andamios del Tejido , Humanos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/química , Andamios del Tejido/química , Células Madre Mesenquimatosas/citología , Animales , Línea Celular Tumoral , Transducción de Señal , Supervivencia Celular , Ingeniería de Tejidos/métodos , Quitosano/química , Fosfatasa Alcalina/metabolismo , Oseointegración , Polímeros/química , PorosidadRESUMEN
PURPOSE/OBJECTIVE: To examine the association of changes in homebound status (i.e., never/rarely leaving the home) with life satisfaction in the first 10 years after traumatic brain injury (TBI). RESEARCH METHOD/DESIGN: We analyzed data from 2,294 individuals with moderate-to-severe TBI from the TBI Model Systems National Database using a longitudinal multilevel model with time-varying predictors to account for within-person changes over time as well as between-person differences. We measured homebound status (defined as leaving the home ≤ 2 days/week) and life satisfaction (defined as the total score on the Satisfaction With Life Scale) at 1, 2, 5, and 10 years post-TBI. We adjusted the models for demographic and injury-related covariates and used inverse probability weighting to account for selection bias. RESULTS: Forty-five (2%) individuals were homebound at all follow-up visits, 523 (22.8%) were homebound at least one follow-up visit, and 1,726 (75.2%) were never homebound. Individuals with TBI who were consistently homebound had > 1 SD lower life satisfaction compared to those who were never homebound, ß = -8.07, 95% confidence interval (CI) = [-9.39, -6.76], p < .001. Individuals who became homebound experienced a significant, but modest, decline in life satisfaction (ß = -2.13, 95% CI = [-2.66, -1.61], p < .001). CONCLUSIONS/IMPLICATIONS: Our results indicate that being homebound and becoming homebound are associated with decreased life satisfaction. Homeboundness is a potentially modifiable target to improve life satisfaction, and elucidation of contributing factors to homebound status will help develop interventions to ameliorate post-TBI homeboundness. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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This review aims to examine the existence of Pseudomonas aeruginosa (P. aeruginosa) and their antibiotic resistance genes (ARGs) in aquatic settings and the alternative treatment ways. P. aeruginosa in a various aquatic environment have been identified as contaminants with impacts on human health and the environment. P. aeruginosa resistance to multiple antibiotics, such as sulfamethoxazole, ciprofloxacin, quinolone, trimethoprim, tetracycline, vancomycin, as well as specific antibiotic resistance genes including sul1, qnrs, blaVIM, blaTEM, blaCTX, blaAIM-1, tetA, ampC, blaVIM. The development of resistance can occur naturally, through mutations, or via horizontal gene transfer facilitated by sterilizing agents. In addition, an overview of the current knowledge on inactivation of Pseudomonas aeruginosa and ARG and the mechanisms of action of various disinfection processes in water and wastewater (UV chlorine processes, catalytic oxidation, Fenton reaction, and ozonation) is given. An overview of the effects of nanotechnology and the resulting wetlands is also given.
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To find out the possibilities of growing white sandalwood in sub-tropical regions of India where farmers facing the problem of water deficit and salinity stress, a RBD experiment was conducted. Sandalwood grown alone and with five selected hosts (Alternanthera sp., Neem, Shisham, Dek and Agarwood) on the basis of prior study under water deficit, salinity stress and combined water deficit and salinity stress. Sandalwood plants were harvested after 180 days of imposing stress treatments. Morphological traits (plant height, collar diameter, shoot fresh and dry biomass) showed significant reduction under water deficit and salinity stress, which were further aggravated under combined water deficit and salinity stress. Studied plant water traits, ionic balance and gas exchange attributes were also reduced by these stresses. While among studied host, Shisham and Dek identified as the best host species under water deficit, salinity and interactive stress by maintaining ion homeostasis, osmotic adjustments and plant water regulation. Results depicted that sandalwood plants cultivated alone were not able to survive under salinity and combined stress conditions and showed poor growth under water deficit and control conditions. Different indices were also calculated based on morpho-physiological and ionic traits and also indicated that sandalwood grown with Dalbergia sissoo and Melia dubia showed higher drought, salt and stress tolerance potential, which made sandalwood adaptable under these stresses. Therefore, the present study signifies the importance of host especially D. sissoo and M. dubia which might be excellent long-term host species for sandalwood cultivation under sub-tropical conditions to thrive under changing environments.
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Objectives: The determinants of progression-free survival (PFS) and overall survival (OS) for higher-grade meningiomas have not been clearly established and to summarize the long-term clinical outcome for patients with grade 2 or 3 meningioma and assess the PFS and OS factors. Materials and Methods: The study included all individuals, who had undergone surgical removal of cerebral meningiomas between 2005 and 2020 and whose histological results suggested a World Health Organization (WHO) grade 2 or grade 3 diseases. Kaplan-Meier curves are plotted to examine tumor control and OS after the follow-up. The reverse Wald logistic regression and Mantel-Cox test were used in multivariate analysis for tumor recurrence and mortality. Results: There were 94 individuals enrolled with 82 having WHO grade 2 tumors and 12 having WHO grade 3 lesions. Gross total resection of the tumor was present in 73 patients (78%), and adjuvant radiotherapy (RT) was administered to 43 (45.7%) individuals. During the course of the study, 17 patients died. The WHO grade of the tumor, the extent of resection, and the absence of bone involvement were all independent predictors of better survival in a multivariate analysis. Furthermore, whereas adjuvant RT after surgery enhanced survival, it was not statistically significant (hazard ratios [95% confidence interval CI] = 1.91 [0.15-23.52] [P = 0.61]). Conclusion: The degree of tumor excision is the strongest predictor of PFS and OS. In the event of a recurrence, rather than opting for upfront radiation, a second surgery with the goal of maximum safe resection should be performed.
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Carbon nanotube-FETs (CNTFETs) have become a potential challenger because of their exceptional electrical properties and compatibility with conventional CMOS technology. The design and study of digitally tunable transconductance amplifiers (DTTAs) using CNTFETs are the main topics of this work. By utilizing the special characteristics of CNTFETs, the suggested DTTA design makes transconductance tunable, providing a versatile method of adjusting amplifier settings without requiring modifications to the hardware architecture. This study provides a complete description of the CNTFET modeling techniques utilized for realistic circuit simulations, along with a detailed analysis of the DTTA based on CNTFETs. The circuit is implemented using a 32 nm CNTFET model and verified results with HSPICE.
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BACKGROUND: The reproductive organ, housing spermatogonial stem cells (SSCs), undergoes ongoing division impacted by the irradiation dosage and exposure duration. Within the male reproductive organ, germ stem cells (spermatogonia) and somatic cells (Sertoli and Leydig cells) are present. Lower doses of ionizing (>4-6 Gy) and non-ionizing radiation (radiofrequency and microwave range 900 MHz - 2.45 GHz) may cause sperm-related issues, while higher doses (15 Gy) may affect Leydig cells and testosterone production. Response to radiation varies with age and pubescence. Spermatogonial stem cells, crucial for regenerating the spermatogenic lineage, express molecular markers like Estrogen receptor, FSH (Follicular Stimulating Hormone) receptor, TLR-4 (Toll-like Receptor-4), TLR-5 (Toll-like Receptor-5), FGF2 (Fibroblast Growth Factor-2), KIT (Receptor Tyrosine Kinase), AT-1 (Angiotensin II Type-1 Receptor), LXRs-γ (Liver X Receptor-γ), TNF-ß (Tumor Necrosis Factor-ß), and PCNA (Proliferating Cell Nuclear Antigen), influencing stem cell activity in testes. OBJECTIVE: This study aimed to review the various available radioprotective agents and their efficacy in targeting the male reproductive system from the available literature. RESULT: Various radioprotective herbal/synthetic/microbial/metallic extracts/formulations/ drugs [Septilin, Silymarin, Organic Turmeric, Oestrogen, Melatonin, Febuxostat, SQGD (Semiquinone glucoside derivative), Rapamycin, Entolimod, Zinc, Selenium, etc.] have been investigated up to exposure, but owing to effectiveness issues, they are unable to fulfil the aim to the fullest of restoring male fertility and normal testosterone levels during such eventuality. CONCLUSION: Further study is needed to optimize these tactics and fill knowledge gaps. Also, the effective components of herbal, synthetic drugs, etc., should be isolated and tested up to clinical levels, paving the way for successful radioprotection and radiomitigation strategies in the male reproductive system.
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The primary issues in the Himalayan Rivers are sediment and cavitation degradation of the hydroelectric power turbine components. During the monsoon season, heavy material is transported by streams in hilly areas like the Himalayas through regular rainfalls, glacial and sub-glacial hydrological activity, and other factors. The severe erosion of hydraulic turbines caused by silt abrasion in these areas requires hydropower facilities to be regularly shut down for maintenance, affecting the plant's overall efficiency. This article provides an in-depth examination of the challenges that can lead to cavitation, silt erosion, and a decrease in the efficiency of various hydroelectric turbines, and it demands attention on the design, manufacture, operation, and maintenance of the turbines. This study's main objective is to critically evaluate earlier theoretical, experimental, and numerical evaluation-based studies (on cavitation and silt erosion) that are provided and addressed throughout the study. As a part of this study, various strategies for mitigating the effects of these problems and elongating the time that turbine may be utilized before they must be replaced have been provided.
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Purpose: To assess the accuracy of freehand cervical C1 C2 screws placement by knock and drill (K and D) technique in craniovertebral anomalous bony anatomy. Materials and Methods: From January 2017 to December 2022, 682 consecutive C1 C2 screws in 215 patients with craniovertebral junction (CVJ) anomalies were enrolled. All patients underwent posterior fixation with K and D technique without any fluoroscopic guidance. The patient's demographic details, clinical details, radiological details, major intraoperative events, and postoperative complications were noted. The screws malposition grades and direction on CT images in the axial and sagittal plane were defined as new per proposed "SGPGI accuracy criteria." All patients had a clinical evaluation at 3-month follow-up. Results: Total 682 C1, C2 screws were placed in 215 patients for CVJ anomalies using K and D technique. The accuracy of screws placement by freehand technique was 84.46% (576/682). So with technique explained the rate of malplacement in simple (16.35%) and complex (15.19%) groups were almost comparable and comparison difference was not significant (P = 0.7005). Conclusion: The freehand technique, as described, is effective in cases of anomalous bony anatomy, and it is mandatory in complex CVJ anomalies. The accuracy of screw placement and VA injury is comparable with major studies. This technique is supposedly cost-effective and less hazardous to both health-care workers and patients.
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This presentation showcases an endoscopic minimally invasive spine surgery (MISS) technique for lumbar interbody fusion. Significantly expanding the scope of Destandau's system within MISS, it serves as a pivotal link to unilateral biportal endoscopy (UBE) for endofusion. The method involves minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) using a 4-mm rigid endoscope through Destandau's system. With the widespread familiarity with Destandau's system and the absence of specialized instrument requirements, this approach is easily adoptable, particularly in resource-limited centers. The favorable clinical and radiological outcomes underscore the effectiveness of this technique, propelling the role of endoscopy in MISS, particularly in endofusion. The video can be found here: https://stream.cadmore.media/r10.3171/2024.1.FOCVID23216.