ABSTRACT
Directly capturing water from the air has become a compelling strategy to secure water resources. Yet, challenges persist with sorption-based hygroscopic materials, such as inadequate water adsorption efficiency, material degradation post-adsorption, and the need for energy input during water collection. This study introduces an alternative category of sorbent materials potentially for atmospheric water harvesting-metal chloride perovskites-that exhibit spontaneous water vapor adsorption and liquid water collection. This water uptake capability stems from the uncoordinated polar ions that form hydrogen bonds with water molecules, while the cubic lattice imparts a solid framework ensuring structural stability and inhibiting hydrolysis. The methylammonium lead chloride perovskite pellets exhibit efficient water collection performance, with a record absorption rate of 0.841 L m-2 h-1 and a total water collection of 3.675 L m-2 within a 7-h cycle. This initiative attempts to provide a new material class candidate for the potential application of passive atmospheric water harvesting.
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Glucose and lipid metabolism dysregulation in skeletal muscle contributes to the development of metabolic disorders. The efficacy of fucoxanthin in alleviating lipid metabolic disorders in skeletal muscle remains poorly understood. In this study, we systematically investigated the impact of fucoxanthin on mitigating lipid deposition and insulin resistance in skeletal muscle employing palmitic acid-induced lipid deposition in C2C12 cells and ob/ob mice. Fucoxanthin significantly alleviated PA-induced skeletal muscle lipid deposition and insulin resistance. In addition, fucoxanthin prominently upregulated the expression of lipid metabolism-related genes (Pparα and Cpt-1), promoting fatty acid ß-oxidation metabolism. Additionally, fucoxanthin significantly increased the expression of Pgc-1α and Tfam, elevated the mtDNA/nDNA ratio, and reduced ROS levels. Further, we identified pyruvate kinase muscle isozyme 1 (PKM1) as a high-affinity protein for fucoxanthin by drug affinity-responsive target stability and LC-MS and confirmed their robust interaction by CETSA, microscale thermophoresis, and circular dichroism. Supplementation with pyruvate, the product of PKM1, significantly attenuated the beneficial effects of fucoxanthin on lipid deposition and insulin resistance. Mechanistically, fucoxanthin reduced glucose glycolysis rate and enhanced mitochondrial biosynthesis and fatty acid ß-oxidation through inhibiting PKM1 activity, thereby alleviating lipid metabolic stress. These findings present a novel clinical strategy for treating metabolic diseases using fucoxanthin.
Subject(s)
Insulin Resistance , Lipid Metabolism , Muscle, Skeletal , Pyruvate Kinase , Xanthophylls , Animals , Mice , Muscle, Skeletal/metabolism , Muscle, Skeletal/drug effects , Xanthophylls/pharmacology , Lipid Metabolism/drug effects , Pyruvate Kinase/metabolism , Pyruvate Kinase/genetics , Male , Humans , Mice, Inbred C57BL , Diet, High-Fat/adverse effectsABSTRACT
Photoactive black-phase formamidinium lead triiodide (α-FAPbI3) perovskite has dominated the prevailing high-performance perovskite solar cells (PSCs), normally for those spin-coated, conventional n-i-p structured devices. Unfortunately, α-FAPbI3 has not been made full use of its advantages in inverted p-i-n structured PSCs fabricated via blade-coating techniques owing to uncontrollable crystallization kinetics and complicated phase evolution of FAPbI3 perovskites during film formation. Herein, a customized crystal surface energy regulation strategy has been innovatively developed by incorporating 0.5â mol % of N-aminoethylpiperazine hydroiodide (NAPI) additive into α-FAPbI3 crystal-derived perovskite ink, which enabled the formation of highly-oriented α-FAPbI3 films. We deciphered the phase transformation mechanisms and crystallization kinetics of blade-coated α-FAPbI3 perovskite films via combining a series of in-situ characterizations and theoretical calculations. Interestingly, the strong chemical interactions between the NAPI and inorganic Pb-I framework help to reduce the surface energy of (100) crystal plane by 42 %, retard the crystallization rate and lower the formation energy of α-FAPbI3. Benefited from multifaceted advantages of promoted charge extraction and suppressed non-radiative recombination, the resultant blade-coated inverted PSCs based on (100)-oriented α-FAPbI3 perovskite films realized promising efficiencies up to 24.16 % (~26.5 % higher than that of the randomly-oriented counterparts), accompanied by improved operational stability. This result represented one of the best performances reported to date for FAPbI3-based inverted PSCs fabricated via scalable deposition methods.
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Common polymeric conductive electrodes, such as polyethylene terephthalate (PET) coated with indium tin oxide, face a major challenge due to their low processing-temperature limits, attributed to PET's low glass transition temperature (Tg) of (70-80 °C). This limitation significantly narrows the scope of material selection, limits the processing techniques applicable to the low Tg, and hinders the ripened technology transfer from glass substrates to them. Addressing the temperature constraints of the flexible substrates is impactful yet underexplored, with broader implications for fields beyond photovoltaics. Here, a new thermal radiation annealing methodology is introduced to address this issue. By applying the above Tg radiation annealing in conjunction with thermoelectric cooling, highly ordered molecular packing on PET substrates is successfully created, which is exclusively unachievable due to PET's low thermal tolerance. As a result, in the context of perovskite solar cells, this approach enables the circumvention of high-temperature annealing limitations of PET substrates, leading to a remarkable flexible device efficiency of 22.61% and a record fill factor of 83.42%. This approach proves especially advantageous for advancing the field of flexible optoelectronic devices.
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Additional organics are generally supplemented in the sulfide-driven autotrophic denitrification system to accelerate the denitrification rate and reduce sulfate production. In this study, different concentrations of sodium acetate (NaAc) were added to the sulfide-driven autotrophic denitrification reactor, and the S0 accumulation increased from 7.8% to 100% over a 120-day operation period. Batch experiments revealed a threefold increase in total nitrogen (TN) removal rate at an Ac--C/N ratio of 2.8 compared to a ratio of 0.5. Addition of organic carbon accelerated denitrification rate and nitrite consumption, which shortened the emission time of N2O, but increased the N2O production rate. The lowest N2O emissions were achieved at the Ac--C/N ratio of 1.3. Stable isotope fractionation is a powerful tool for evaluating different reaction pathways, with the 18ε/15ε values in nitrate reduction ranging from 0.5 to 1.0. This study further confirmed that isotope fractionation can reveal denitrifying nutrient types, with the 18ε (isotopic enrichment factor of oxygen)/15ε (isotopic enrichment factor of nitrogen) value approaching 1.0 for autotrophic denitrification and 0.5 for heterotrophic denitrification. Additionally, the 18ε/15ε values can indicate changes in nitrate reductase. There is a positive correlation between the 18ε/15ε values and the abundance of the functional gene napA, and a negative correlation with the abundance of the gene narG. Moreover, 18ε and 15ε were associated with changes in kinetic parameters during nitrate reduction. In summary, the combination of functional gene analysis and isotope fractionation effectively revealed the complexities of mixotrophic denitrification systems, providing insights for optimizing denitrification processes.
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Plant-derived sugars and lipids are key nutritional sources for plant associated fungi. However, the relationship between utilization of host-derived sugars and lipids during development of the symbiotic association remains unknown. Here we show that the fungus Metarhizium robertsii also needs plant-derived lipids to develop symbiotic relationship with plants. The fatty acid binding proteins FABP1 and FABP2 are important for utilization of plant-derived lipids as the deletion of Fabp1 and Fabp2 significantly reduced the ability of M. robertsii to colonize rhizoplane and rhizosphere of maize and Arabidopsis thaliana. Deleting Fabp1 and Fabp2 increased sugar utilization by upregulating six sugar transporters, and this explains why deleting the monosaccharide transporter gene Mst1, which plays an important role in utilization of plant-derived sugars, had no impact on the ability of the double-gene deletion mutant ΔFabp1::ΔFabp2 to colonize plant roots. FABP1 and FABP2 were also found in other plant-associated Metarhizium species, and they were highly expressed in the medium using the tomato root exudate as the sole carbon and nitrogen source, suggesting that they could be also important for these species to develop symbiotic relationship with plants. In conclusion, we discovered that utilization of plant-derived sugars and lipids are coupled during colonization of rhizoplane and rhizosphere by M. robertsii.
Subject(s)
Arabidopsis , Metarhizium , Plant Roots , Rhizosphere , Zea mays , Metarhizium/genetics , Metarhizium/metabolism , Arabidopsis/microbiology , Arabidopsis/genetics , Plant Roots/microbiology , Zea mays/microbiology , Symbiosis/genetics , Fatty Acid-Binding Proteins/genetics , Fatty Acid-Binding Proteins/metabolism , Lipid Metabolism/genetics , Fungal Proteins/genetics , Fungal Proteins/metabolism , Sugars/metabolismABSTRACT
Objectives: This study aimed to determine the occurrence rate of malalignment of tibial prosthesis and explore the influencing factors. Methods: 296 patients from Southern China who underwent total knee arthroplasty (TKA) were selected as the research objects. Their general demographic data were recorded. The tibial bowing angle (TBA), tibial length, medial proximal tibial angle (MPTA), tibial plateau shift angle (TPSA), tibial bone loss, lateral distal tibial angle, and overall width of tibial plateau and widths of medial and lateral tibial plateau were measured before TKA. The tibial component coronal alignment angle (TCCA) was measured after the operation. Malalignment of the tibial prosthesis was defined as TCCA <87° or TCCA >93°. Tibial bowing was indicated by TBA >2°, and lateral bowing was recorded as +. The correlations of TCCA with demographic data and pre-operation imaging measurement parameters were statistically analyzed. Results: Bivariate correlation analysis revealed negative correlations between TCCA and TBA (r = -0.602, P < 0.001) and TPSA (r = -0.304, P < 0.001), and a positive correlation with MPTA (r = -0.318, P < 0.001). Multivariate linear regression analysis demonstrated a significant negative correlation between TCCA and TBA (P < 0.001). The occurrence rate of malalignment of tibial prosthesis was 12.37 %. The occurrence rates of malalignment were 22.54 % in the tibial bowing group and 6.87 % in the non-tibial bowing group, showing statistical differences (P < 0.001). Conclusion: The malalignment rate of tibial prosthesis among Southern Chinese patients is relatively high, possibly attributed to the tibial anatomy anomalies, particularly the tibial bowing. The entry point should be determined based on tibial morphology.
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Bacterial infection and delayed osseointegration are two major challenges for titanium-based orthopedic implants. In the present study, we developed a functionalized titanium implant Ti-M@A by immobilizing antimicrobial peptide (AMP) HHC36-loaded diselenide-bridged mesoporous silica nanoparticles (MSNs) on the surface, which showed good long-term and mechanical stability. The functionalized implants can realize the sustained release of AMP over 30 days and exhibit over 95.71 % antimicrobial activity against four types of clinical bacteria (S. aureus, E. coli, P. aeruginosa and MRSA), which arose from the capability to destroy the bacterial membranes. Moreover, Ti-M@A can efficiently inhibit the biofilm formation of the bacteria. The functionalized implants can also significantly promote the osteogenic differentiation of mouse bone marrow-derived mesenchymal stem cells (mBMSCs) because of the Se in MSNs. Notably, it can trigger macrophages toward M2 polarization in vitro by scavenging ROS in LPS-activated macrophages. Consequently, in vivo assays with infection and non-infection bone defect models demonstrated that such bioactive implants can not only kill over 98.82 % of S. aureus, but also promote osseointegration. Hence, this study provides a combined strategy to resolve bacterial infection and delayed osseointegration for titanium implants.
Subject(s)
Bacterial Infections , Nanoparticles , Mice , Animals , Osseointegration , Titanium/pharmacology , Staphylococcus aureus , Osteogenesis , Silicon Dioxide , Escherichia coli , Bacteria , Inflammation , Antimicrobial Peptides , Surface PropertiesABSTRACT
A feature of the Chinese soft-shelled turtle (Pelodiscus sinensis) is seasonal spermatogenesis; however, the underlying molecular mechanism is not well clarified. Here, we firstly cloned and characterized P. sinensis DKKL1, and then performed comparative genomic studies, expression analysis, and functional validation. P. sinensis DKKL1 had 2 putative N-glycosylation sites and 16 phosphorylation sites. DKKL1 also had classic transmembrane structures that were extracellularly localized. DKKL1's genetic distance was close to turtles, followed by amphibians and mammals, but its genetic distance was far from fishes. DKKL1 genes from different species shared distinct genomic characteristics. Meanwhile, they were also relatively conserved among themselves, at least from the perspective of classes. Notably, the transcription factors associated with spermatogenesis were also identified, containing CTCF, EWSR1, and FOXL2. DKKL1 exhibited sexually dimorphic expression only in adult gonads, which was significantly higher than that in other somatic tissues (P < 0.001), and was barely expressed in embryonic gonads. DKKL1 transcripts showed a strong signal in sperm, while faint signals were detected in other male germ cells. DKKL1 in adult testes progressively increased per month (P < 0.05), displaying a seasonal expression trait. DKKL1 was significantly downregulated in testes cells after the sex hormones (17ß-estradiol and 17α-methyltestosterone) and Wnt/ß-catenin inhibitor treatment (P < 0.05). Likewise, the Wnt/ß-catenin inhibitor treatment dramatically repressed CTCF, EWSR1, and FOXL2 expression. Conversely, they were markedly upregulated after the 17ß-estradiol and 17α-methyltestosterone treatment, suggesting that the three transcription factors might bind to different promoter regions, thereby negatively regulating DKKL1 transcription in response to the changes in the estrogen and androgen pathways, and positively controlling DKKL1 transcription in answer to the alterations in the Wnt/ß-catenin pathway. Knockdown of DKKL1 significantly reduced the relative expression of HMGB2 and SPATS1 (P < 0.01), suggesting that it may be involved in seasonal spermatogenesis of P. sinensis through a positive regulatory interaction with these two genes. Overall, our findings provide novel insights into the genome evolution and potential functions of seasonal spermatogenesis of P. sinensis DKKL1.
Subject(s)
Turtles , Animals , Male , Turtles/genetics , Turtles/metabolism , beta Catenin/metabolism , Methyltestosterone/metabolism , Semen , Spermatogenesis/genetics , Estradiol/metabolism , Genomics , MammalsABSTRACT
Ultrafiltration (UF) is widely used in wastewater reclamation treatments. Conventional backwashing is usually performed at regular time intervals (10-120 min) with permeate and without the addition of chemicals. Chemical enhanced backwashing (CEB) is usually applied after 70-90 filtration cycles with added chemicals. These cleaning methods cause membrane fouling and require costly chemicals. Instead of conventional backwashing, we propose herein a new backwashing method involving backwashing the effluent with low doses of sodium hypochlorite (NaClO) named as BELN. The performance and cost of UF backwashing were investigated with Beijing wastewater reclamation treatment. The results showed that the transmembrane pressure (TMP) increased from 33.2 to 48.2 kPa during hydraulic backwashing after 80 filtration cycles but increased from 33.3 to 39.3 kPa during backwashing with a low NaClO content of 20 mg/L. It was also noticed that the hydraulic-irreversible fouling index decreased from 5.58 × 10-3 m2/L to 3.58 × 10-3 m2/L with the new method. According to the three-dimensional fluorescence excitation-emission (3D-EEM), the response increased from 11.9 to 15.2% with BELN. Protein-like material was identified as the main component causing membrane fouling by blocking the membrane pores. The results indicated that the low dosage of NaClO effectively stripped the fouling layer. Finally, based on an economic evaluation, the capacity of the UF process was increased from 76,959 to 109,133 m3/d with the new method. The amount of NaClO consumed for Beijing wastewater reclamation treatment was similarly compared with the conventional backwashing in per year under BELN. The new method has good potential for application.
Subject(s)
Ultrafiltration , Water Purification , Ultrafiltration/methods , Wastewater , Membranes, Artificial , Filtration , Water Purification/methodsABSTRACT
Confined semiconducting CuSe quantum dots with abundant Se vacancies are synthesized by pulsed laser deposition with in situ vacuum annealing. With the presence of Se vacancies, the photogenerated charge recombination is suppressed by the self-introduced in-gap trapping states, thus enhancing the photoelectrocatalytic activity under solar illumination.
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The efficient functioning and stability of a perovskite photoactive layer are paramount to the performance of solar cell devices. Here, we present a protocol for the synthesis of a high-performance exemplified methylammonium lead iodide (CH3NH3PbI3 or MAPbI3) perovskite photoactive layer. We describe steps for preparing the requisite ratios of the precursor powders, synthesizing MAPbI3 single crystals, and selecting a suitable preparation technique. We then detail a flexible doping strategy for the perovskite photoactive layer. For complete details on the use and execution of this protocol, please refer to Wang and Wu (2020, 2022, 2023).1,2,3.
Subject(s)
Calcium Compounds , Oxides , Titanium , Crystallization , SolventsABSTRACT
Interlayer electric fields in two-dimensional (2D) materials create photoelectron protecting barriers useful to mitigate electron-hole recombination. However, tuning the interlayer electric field remains challenging. Here, carbon-doped Bi3O4Cl (C:Bi3O4Cl) nanosheets are synthesized using a gas phase protocol, and n-type carriers are acquired as confirmed by the transconductance polarity of nanosheet field effect transistors. Thin C:Bi3O4Cl nanosheets show excellent 266 nm photodetector figures of merit, and an avalanche-like photocurrent is demonstrated. Decaying behaviors of photoelectrons pumped by a 266 nm laser pulse (266 nm photoelectrons) are observed using transient absorption spectroscopy, and a significant 266 nm photoelectron lifetime quality in C:Bi3O4Cl is presented. Built C:Bi3O4Cl models suggest that the interlayer electric field can be boosted by two different carbon substitutions at the inner and outer bismuth sites. This work reports a facile approach to increase the interlayer electric field in Bi3O4Cl for future UV-C photodetector applications.
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Neurodegenerative diseases (ND) have received increasing attention due to their irreversibility, but there is still no means to completely cure ND in clinical practice. Mindfulness therapy (MT), including Qigong, Tai Chi, meditation, and yoga, etc., has become an effective complementary treatment modality in solving clinical and subclinical problems due to its advantages of low side effects, less pain, and easy acceptance by patients. MT is primarily used to treat mental and emotional disorders. In recent years, evidence has shown that MT has a certain therapeutic effect on ND with a potential molecular basis. In this review, we summarize the pathogenesis and risk factors of Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), relating to telomerase activity, epigenetics, stress, and the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB) mediated inflammatory response, and analyze the molecular mechanism basis of MT to prevent and treat ND, to provide possible explanations for the potential of MT treatments for ND.
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With the development of location-based service (LBS), indoor positioning based on pedestrian dead reckoning (PDR) has become a hot research topic. Smartphones are becoming more popular for indoor positioning. This paper proposes a two-step robust-adaptive-cubature Kalman filter (RACKF) algorithm based on smartphone micro-electro-mechanical-system (MEMS) sensor fusion for indoor positioning. To estimate pedestrian heading, a quaternion-based robust-adaptive-cubature Kalman filter algorithm is proposed. Firstly, the model noise parameters are adaptively corrected based on the fading-memory-weighting method and the limited-memory-weighting method. The memory window of the limited-memory-weighting algorithm is modified based on the characteristics of pedestrian walking. Secondly, an adaptive factor is constructed based on the partial state inconsistency to overcome filtering-model deviation and abnormal disturbances. Finally, to identify and control the measurement outliers, the robust factor based on maximum-likelihood estimation is introduced into the filtering to enhance the robustness of heading estimation and support more robust dynamic-position estimation. In addition, based on the accelerometer information, a nonlinear model is constructed and the empirical model is used to estimate the step length. Combining heading and step length, the two-step robust-adaptive-cubature Kalman filter is proposed to improve the pedestrian-dead-reckoning method, which enhances the adaptability and robustness of the algorithm and further improves the accuracy of the plane-position solution. The adaptive factor based on the prediction residual and the robust factor based on the maximum-likelihood estimation are introduced into the filter to improve the adaptability and robustness of the filter, reduce the positioning error, and improve the accuracy of the pedestrian-dead-reckoning method. Three different smartphones are used to validate the proposed algorithm in an indoor environment. Additionally, the experimental results confirm the algorithm's effectiveness. From the results of the three smartphones, the root mean square error (RMSE) of the indoor-positioning results obtained by the proposed method is about 1.3-1.7 m.
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OBJECTIVE: To investigate the clinical effect of double pulley combined with suture bridge in the treatment of comminuted fracture of the lower pole of the patella. METHODS: From January 2018 to June 2020, 15 patients with comminuted fracture of the lower pole of the patella were treated with double pulley and suture bridge technology, including 9 males and 6 females, aged 28 to 68 years old with an average of (42.4±9.6) years old. All patients had obvious knee joint pain and limited movement after injury. All knee joints were examined by X-ray and CT, which confirmed that they were all comminuted fractures at the lower level of the patella. After operation, X-ray films of the knee joint were taken regularly to understand the fracture healing, the Insall Salvati index was measure, the range of motion of the joint was recorded, and the function of the knee joint was evaluateed by the Bostman scoring system. RESULTS: All the 15 patients were followed up for 7 to 24 months with an average of (11.4±4.2) months, and there was no obvious anterior knee pain. At the last follow-up, the knee joint range of motion of the affected limb was 105° to 140° with an average of (128.5±12.8) °, and the Insall Salvati index was 0.79 to 1.12 with an average of (0.92±0.18). The X-ray film showed that the patella was bone healing, and no anchor fell off, broken, or displaced fracture block was found. Bostman patellar fracture function score was 27.85±2.06, 13 cases were excellent, 2 cases were good. CONCLUSION: Double pulley technique combined with suture bridge technique is reliable for reduction and fixation of comminuted fracture of the lower pole of patella, and patients can start functional exercise early after operation.
Subject(s)
Fractures, Bone , Fractures, Comminuted , Male , Female , Humans , Adult , Middle Aged , Aged , Fractures, Comminuted/surgery , Fracture Fixation, Internal/methods , Patella/surgery , Patella/injuries , Bone Wires , Fractures, Bone/surgery , Sutures , Treatment OutcomeABSTRACT
Introduction: Bone morphogenetic proteins (BMPs) play a crucial role in bone formation and differentiation. Recent RNA-Seq results suggest that BMPs may be involved in the sex differentiation of P. sinensis, yet more relevant studies about BMPs in P. sinensis are lacking. Methods: Herein, we identified BMP gene family members, analyzed the phylogeny, collinear relationship, scaffold localization, gene structures, protein structures, transcription factors and dimorphic expression by using bioinformatic methods based on genomic and transcriptomic data of P. sinensis. Meanwhile, qRT-PCR was used to verify the RNA-Seq results and initially explore the function of the BMPs in the sex differentiation of P. sinensis. Results: A total of 11 BMP genes were identified, 10 of which were localized to their respective genomic scaffolds. Phylogenetic analysis revealed that BMP genes were divided into eight subfamilies and shared similar motifs ("WII", "FPL", "TNHA", "CCVP", and "CGC") and domain (TGF-ß superfamily). The results of the sexually dimorphic expression profile and qRT-PCR showed that Bmp2, Bmp3, Bmp15l, Bmp5, Bmp6 and Bmp8a were significantly upregulated in ovaries, while Bmp2lb, Bmp7, Bmp2bl and Bmp10 were remarkable upregulated in testes, suggesting that these genes may play a role in sex differentiation of P. sinensis. Discussion: Collectively, our comprehensive results enrich the basic date for studying the evolution and functions of BMP genes in P. sinensis.
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OBJECTIVES: To compare the dose volume of the target area and the toxicity of pelvic bone marrow-sparing intensity-modulated radiotherapy (PBMS-IMRT) with routine IMRT in patients undergoing radiochemotherapy for cervical cancer. MATERIAL AND METHODS: Forty patients with indications for adjuvant radiochemotherapy after cervical cancer surgery were selected and randomly divided into IMRT (n = 20) and PBMS-IMRT (n = 20) groups to observe and record the toxicity and its severity in the blood, gastrointestinal tract, and genitourinary system. RESULTS: There was no significant difference in the target area conformity index (CI) or homogeneity index (HI) between the two groups (p > 0.05). The pelvic bone V10-V50 in the PBMS-IMRT group were lower than those in the IMRT group (p < 0.05), and there was lower hematological toxicity (p < 0.05) and fewer delays or interruptions in chemotherapy and/or radiotherapy (p < 0.05) in the PBMS-IMRT group. The toxicity to the gastrointestinal and genitourinary systems in the two groups was not significantly different (p > 0.05). CONCLUSIONS: PBMS-IMRT significantly reduced the dose volume of the pelvic bone marrow, thereby reducing the incidence of bone marrow suppression. However, it had no significant impact on the gastrointestinal or genitourinary systems.
Subject(s)
Pelvic Bones , Radiotherapy, Intensity-Modulated , Uterine Cervical Neoplasms , Female , Humans , Bone Marrow , Chemoradiotherapy, Adjuvant , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/adverse effects , Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms/drug therapyABSTRACT
OBJECTIVE: Adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC) are the two most frequent malignancies of salivary glands. This study aims to explore the expression and migration of LAG3, TIM3, and A2aR in AdCC and MEC, and the potential relationship with oncogenic signaling molecules and immunosuppressive cytokines. MATERIALS AND METHODS: Custom made human salivary gland tissue microarrays included 81 AdCCs, 52 MECs, 76 normal salivary glands (NSG), and 14 pleomorphic adenoma (PMA) samples. Immunohistochemical analysis of lymphocyte activation gene 3 (LAG3), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), adenosine 2a receptor (A2aR), oncogenic phosphorylated S6 kinase (p-S6) and ERK1/2 (p-ERK1/2 ), and TGF-ß1 was performed with salivary gland tissue microarrays of human samples. The correlation of the immunostaining was analyzed based on a digital pathological system, and data were evaluated by hierarchical cluster. Further in vitro studies of knockdown immune checkpoints LAG3, TIM3, and A2aR were carried out by siRNA transfection. RESULTS: The expression levels of LAG3, TIM3, and A2aR were remarkably increased in AdCC and MEC, compared with NSG and PMA samples, but were independent of pathology grade. They were closely correlated with TGF-ß1, slightly related to p-ERK1/2 and p-S6. After the knockdown of immune checkpoints LAG3, TIM3, and A2aR, the migration of SACC-LM cell line was significantly reduced. CONCLUSIONS: These results suggested that LAG3, TIM3, and A2aR are overexpressed in AdCC and MEC, may promote migration of SACC-LM cell and correlated with TGF-ß1 and oncogenic signaling pathways.