Retinoic acid receptor-related orphan receptor alpha and synthetic RORα agonist against invasion and metastasis in tongue squamous cell carcinoma.

Retinoic acid receptor-related orphan receptor alpha (RORα), an essential tumor suppressor in a range of human malignancies, is classified as a member of the orphan nuclear receptor family. The most prevalent form of oral cancer, tongue squamous cell carcinoma (TSCC) is characterized by its severe malignancy and unfavorable prognosis. However, the extent to which its tumorigenesis mechanisms are associated with RORα expression levels is still not fully understood. The objective of this study was to examine the molecular mechanisms by which RORα is involved in TSCC. Through the use of immunohistochemistry (IHC), it was discovered that the expression level of RORα was significantly downregulated in TSCC tissues when compared to adjacent normal tissues in this study. To further investigate the role of RORα in TSCC, we activated the expression of RORα in human TSCC cell line (SCC9 cells) by transfecting RORα cDNA and using the selective RORα agonist SR1078. The results show that RORα can significantly inhibit the invasion, migration, proliferation, and adhesion of TSCC cells and induce cell apoptosis. In addition, xenograft models confirmed the conclusion that stable activation or treatment with SR1078 to increase RORα content significantly inhibited tumor growth and development. Taken together, this study provides solid evidence for the inhibitory role of RORα in the progression of TSCC. In addition, the preliminary application results of SR1078 in TSCC show that SR1078 is expected to be a potential therapeutic medication for TSCC. These findings provide innovative perspectives on the development of potential biomarkers and agents for TSCC therapy. The objective is to introduce novel strategy and alternatives for the prevention and treatment of TSCC.

OsHRZ1 negatively regulates rice resistant to Magnaporthe oryzae infection by targeting OsVOZ2.

Rice blast disease caused by Magnaporthe oryzae significantly reduces yield production. Blast resistance is closely associated with iron (Fe) status, but the mechanistic basis linking iron status to immune function in rice remains largely unknown. Here, iron-binding haemerythrin RING ubiquitin ligases OsHRZ1 was confirmed to play key roles in iron-mediated rice blast resistance. The expression of OsHRZ1 was suppressed by M. oryzae inoculation and high iron treatment. Both mutants of OsHRZ1 enhanced rice resistance to M. oryzae. OsPR1a was up-regulated in OsHRZ1 mutants. Yeast two-hybrid, bimolecular fluorescence complementation, and Co-IP assay results indicated that OsHRZ1 interacts with Vascular Plant One Zinc Finger 2 (OsVOZ2) in the nucleus. Additionally, the vitro ubiquitination assay indicated that OsHRZ1 can ubiquitinate OsVOZ2 and mediate the degradation of OsVOZ2. The mutants of OsVOZ2 showed reduced resistance to M. oryzae and down-regulated the expression of OsPR1a. Yeast one-hybrid, EMSA, and dual-luciferase reporter assay results indicated that OsVOZ2 directly binds to the promoter of OsPR1a, activating its expression. In summary, OsHRZ1 plays an important role in rice disease resistance by mediated degradation of OsVOZ2 thus shaping PR gene expression dynamics in rice cells. This highlights an important link between iron signaling and rice pathogen defenses.

Research progress of the effects of bisphenol analogues on the intestine and its underlying mechanisms: A review.

Bisphenol A (BPA) and its analogues have prompted rising concerns, especially in terms of human safety, due to its broad use and ubiquity throughout the ecosystem. Numerous studies reported various adverse effects of bisphenols, including developmental disorders, reproductive toxicity, cardiovascular toxicity, and so on. There is increasing evidence that bisphenols can enter the gastrointestinal tract. Consequently, it is important to investigate their effects on the intestine. Several in vivo and in vitro studies have examined the impacts of bisphenols on the intestine. Here, we summarized the literature concerning intestinal toxicity of bisphenols over the past decade and presented compelling evidence of the link between bisphenol exposure and intestinal disorders. Experiment studies revealed that even at low levels, bisphenols could promote intestinal barrier dysregulation, disrupt the composition and diversity of intestinal microbiota as well as induce an immunological response. Moreover, possible underlying mechanisms of these effects were discussed. Because of a lack of empirical data, the potential risk of bisphenol exposure in humans is still unidentified, particularly regarding intestinal disorders. Thus, we propose to conduct additional epidemiological investigations and animal experiments to elucidate the associations between bisphenol exposure and human intestinal health and reveal underlying mechanisms to develop preventative and therapeutic techniques.

Ultrasound-guided percutaneous micro-drainage tube irrigation combined with high negative pressure tube drainage versus debridement with closed suction irrigation for treating deep surgical site infection after spinal surgery.

It is difficult to avoid deep surgical site infection after spinal surgery. Debridement combined with closed suction irrigation (CSI) and other treatment methods lead to greater trauma and lower satisfaction. We developed a new method for the treatment of SSI, which has the advantages of less invasiveness and lower cost. The cohort of this retrospective study comprised 26 patients with SSI after undergoing spinal surgery in our hospital from August 2017 to March 2022. The patients were divided into CSI and microtube drainage group according to treatment methods. The durations of antibiotic use and hospital stay, hospitalization costs, and functional scores during follow-up were compared between the two groups. The only baseline characteristic that differed between the two groups was sex. Infection was controlled in both groups and there were no recurrences during follow-up. However, the length of hospital stay after the first operation and the total length of stay were significantly greater in the CSI group. Hospitalization costs and antibiotic costs were significantly higher in the CSI group. Additionally, the duration of intravenous antibiotic use was significantly longer in the CSI group. Both the CSI and microtube drainage groups had significantly improved of Short Form Health Survey (SF-36) scores 6 months postoperatively. However, 3 months postoperatively, SF-36 scores were significantly lower in the CSI group. Compared with debridement followed by CSI, percutaneous micro-drainage tube irrigation combined with high negative pressure tube drainage is a more efficient and economical means of treating SSI after spinal surgery.

Risk factors for incisional complications after lumbar internal fixation via posterior midline approach: A case-control study of 455 consecutive cases.

To analyse the clinical data of patients who developed incisional complications and those who did not develop incisional complications after lumbar internal fixation, and investigate the risk factors for incisional complications in patients after lumbar internal fixation with posterior midline incision. A standardised data collection form was used to collect the clinical data of patients who were admitted and underwent lumbar internal fixation in our hospital from July 2018 to July 2021. Patients who experienced any one of the incisional complications, such as incision exudates, swelling, blisters, bruising, superficial/deep incisional infections, poor healing and scarring, after surgery were included in the incisional complication group, and patients who did not develop the above-mentioned incisional complications were included in the control group. Univariate logistic regression analysis was first performed to identify potential risk factors, significant factors from univariate analysis were then included in multivariable logistic regression analysis to identify independent risk factors for incisional complications after lumbar spine surgery. Among 455 patients included in the study, postoperative incision complications occurred in 82 patients, with an incidence rate of 18.02%. Multivariate regression analysis identified seven independent risk factors for incisional complications: age, body mass index, preoperative albumin level, hypertension, diabetes mellitus, operation time and local anaesthetic infiltration at the incision site after surgery. Our findings documented that age, body mass index, preoperative albumin level, hypertension, diabetes mellitus, operation time, and postoperative local anaesthetic infiltration at the incision site were risk factors for incisional complications after lumbar internal fixation with posterior median incision. Awareness of these risk factors can enable surgeons to develop a more appropriate perioperative management plan for patients undergoing lumbar internal fixation, thus helping them recover faster.

Down-regulation of MAPK pathway alleviates TRPV4-mediated trigeminal neuralgia by inhibiting the activation of histone acetylation.

Our objective of this study is to determine the molecular mechanism of MAPKs (mitogen activated protein kinase systems) on TRPV4 (transient receptor potential vanilloid 4)-mediated trigeminal neuralgia (TN). Partial chronic constriction injury of the infraorbital nerve (CCI-ION) ligation model was used in this research. When treated with antagonists of p38, JNK or ERK, the mechanical hyperalgesia threshold, nerve fiber disorder, myelinoclasis, and Schwann cells proliferation could be reversed. RT-PCR (real-time quantitative polymerase chain reaction), Western blot and IHC (immunohistochemistry) showed that TRPV4 mRNA and protein levels, TRPV4-positive cells and small positive neurons decreased remarkably in TN group treated with antagonists of p38, JNK or ERK. ELISA (enzyme-linked immunosorbent assay) was performed to discover inhibition of MAPK pathway can down-regulate the expression of HATs (histone acetyltransferases), and up-regulate the expression of HDACs (histone deacetylases) in TN, thus inhibiting histone acetylation. Finally, Western blot was performed to identify the phosphorylation status of p38, JNK and ERK, finding decreased phosphorylation forms in antagonists treated TN groups compared with TN groups. Based on the above investigation method, on a whole, our study showed that down-regulation of MAPK pathway could alleviate TRPV4-mediated trigeminal neuralgia, via inhibiting the activation of histone acetylation.

Influence of Patellar Morphology Classified by Wiberg Classification on Knee Joint Function and Patellofemoral Tracking After Total Knee Arthroplasty Without Patellar Resurfacing.

BACKGROUND: To evaluate the influence of patellar morphology on knee joint function and patellofemoral tracking in patients with primary osteoarthritis after total knee arthroplasty (TKA) without patellar resurfacing. METHODS: We performed a retrospective study of 156 patients with primary osteoarthritis who underwent TKA without patellar resurfacing from April 2018 to July 2019. As per Wiberg classification, patients were divided into Wiberg type I (group A, n = 38), II (group B, n = 88), and III (group C, n = 30) groups. The clinical data, postoperative follow-up data, and radiological data between three groups were compared. RESULTS: There was no statistically significant difference in the HSS score and Feller score between the three groups before surgery and at each follow-up point after surgery (P > .05). At the last follow-up, there were no significant differences in the height and relative thickness of the patella between the three groups (P > .05). However, the incidence of anterior knee pain was significantly higher in group C than in the group B (P < .05). The patellar tilt angle was significantly larger in group C than in the groups A and B (both P < .05). The patellar facet angle was significantly larger in group A than in group B and C, which was also significantly larger in group B than in group C (both P < .05). CONCLUSION: Patients with three different morphologic types of the patella both exhibited improved knee joint function after TKA, however, patients with Wiberg type Ⅲ patella were more prone to have poor patellofemoral tracking and anterior knee pain after surgery.

Casimir torque and force in anisotropic saturated ferrite three-layer structure.

Based on the scattering formalism and transfer matrix method, we calculate the Casimir energy in multilayer system containing general anisotropic media and apply the result to the anisotropic saturated ferrite three-layer structure. We investigate the stable equilibrium resulting from repulsive Casimir force in the three-layer anisotropic ferrite structure, focusing on the control of the equilibrium position by means of the external magnetic field, which might provide possibility for Casimir actuation under external manipulation. Furthermore, we propose a Casimir torque switch where the torque acting on the intermediate layer can be switched on and off by tuning the relative orientation between the external magnetic fields applied on the outer ferrite layers. The relation between the feature of torque-off/torque-on state and the weak/strong anisotropy of the ferrite is studied. These findings suggest potential application of Casimir torque in, e.g., cooling the rotation of a thin slab in micromachining process via external magnetic field.

Low Concentrations of Tetrabromobisphenol A Disrupt Notch Signaling and Intestinal Development in in Vitro and in Vivo Models.

Tetrabromobisphenol A (TBBPA) was recently reported to upregulate Notch target gene expression in embryonic stem cells differentiating to neurons in vitro, implying activation on Notch signaling, a crucial signaling involved in multiple organ development and homeostasis.The present study aimed to determine whether TBBPA at low concentrations can disrupt Notch signaling in the intestine and subsequently its development using in vitro and in vivo models, given TBBPA uptake mainly via the intestine. In rat intestinal epithelium cells (IEC-6), an in vitro model for intestinal development and homeostasis, we found 5-500 nM TBBPA upregulated Notch-related gene expression and stimulated cell proliferation as well as the growth of microvilli in a linear concentration-dependent manner. When Notch inhibitor DAPT had no obvious effects on all end points, DAPT significantly antagonized all changes caused by TBBPA, indicating that TBBPA activated Notch signaling in IEC-6 cells and subsequently stimulated cell proliferation and differentiation. Then we employed Xenopus laevis, an ideal model species for intestinal development with the strong similarities to mammals, to further confirm the action of TBBPA in vivo. Expectedly, we observed the stimulatory effects of TBBPA on Notch signaling and cell proliferation and differentiation in X. laevis intestines, which agrees with the results in vitro. Antagonistic actions of Notch inhibitor DBZ on TBBPA-caused intestinal changes show that TBBPA affected intestinal development via disrupting Notch signaling. Interestingly, TBBPA stimulated cell differentiation into secretory cells, which is generally believed to be regulated by Wnt signaling, suggesting disruption of Wnt signaling besides Notch signaling. All the results for the first time demonstrate that TBBPA at low concentrations, including environmentally relevant concentrations, disrupt Notch signaling and subsequently affect intestinal development by altering cell proliferation and differentiation in vertebrates. Our study highlights the intestine as a new target of TBBPA and broaden our understanding of developmental toxicity of TBBPA.

Photonic quantization and encoding scheme with improved bit resolution based on waveform folding.

Taylor's scheme for photonic quantization and encoding based on Mach-Zehnder modulators (MZMs) requires that the employed MZMs have geometrically scaled half-wave voltages (Vπ), which is impractical even with the state-of-art photonic fabrication techniques when the desired bit resolution is greater than 3 or 4 bits. The approaches based on the phase-shifting of modulation transfer functions eliminate the need of geometrically scaled Vπ, but they realize lower resolution than Taylor's scheme as the realized resolution is log2(2N), but not N as in Taylor's scheme, where N is the number of optical channels (or MZMs). In this paper, we propose a novel photonic quantization and encoding scheme based on waveform folding using rectifier circuits, which aims to realize higher resolution with less MZMs (and less Vπ). In our design, a 4-bit quantization can be achieved using 2 MZMs with identical Vπ with the help of two rectifiers. A proof-of-concept experiment is implemented, which fully verifies the correctness of the approach. The scheme is modular extendable, i. e. an 8-bit quantization can be realized by using 4 MZMs (with 2 different Vπ), and 12-bit can be realized by using 6 MZMs (with 3 different Vπ). The impact of the rectifiers' bandwidth on the system performance is also investigated. As less MZMs are employed and lower requirement on Vπ scaling, the proposed design provides a promising solution for high-performance photonic analog-to-digital conversion.

Numerical investigations of synchronization and communication based on an electro-optic phase chaos system with concealment of time delay.

A modified electro-optic phase chaos system that can conceal time delay (TD) and allows for unidirectional message transmission, is numerically investigated. The configuration includes two cascaded delay loops, and the parallel-coupled microresonators (PCMRs) in one of two loops result in a frequency-dependent group delay. The largest Lyapunov exponent (LLE), Lempel-Ziv complexity (LZC) and permutation entropy (PE) are used to distinguish the chaotic behavior and the degree of complexity in a time series, and the autocorrelation function (ACF) and the delayed mutual information (DMI) are plotted to extract the TD. The corresponding diagrams show that in the electro-optic system phase chaos with high complexity can occur within a certain range of feedback strength. The diagrams also show that, at a fixed feedback strength, the effect of the TD concealment becomes quite good with an increase in the number of PCMRs. The numerical simulation also reveals that the delayed chaotic dynamics can be identically synchronized, and the synchronization solution is robust. Moreover, based on the coherence of Mach-Zehnder interferometers, we convert the phase variations of the transmitter outputs and the receiver into the corresponding intensity variations, so the synchronization error of the two-phase chaotic series can be monitored. At last, we can successfully decipher the message introduced on the transmitting end of a link. In this scheme, the feedback TD has been concealed, which prevents eavesdroppers from listening and makes the proposed chaotic communication system secure.

Point-to-multipoint and ring network communication based on chaotic semiconductor lasers with optical feedback.

In this paper, two configurations of point-to-multipoint (PTM) and ring networks, based on the chaotic semiconductor laser subject to optical feedback, are investigated. A bifurcation diagram and the maximum Lyapunov exponent in the system have been used to distinguish the existence of chaos, and the complex degree of chaotic output is measured through Lempel-Ziv complexity. These results show that feedback strength has a significant effect on the dynamics of the system, namely, an increase in it can induce the system to enter into chaos. In the PTM model, it can be seen that the arbitrary receiver laser (RL) and central transmitter laser (TL) are identically synchronized, and moreover, the synchronization solutions are robust; the message can be encoded by modulating the bias current of the central TL, and at each RL end, the message from TL can be simultaneously recovered by monitoring the power error between RL and TL. As a result, the unidirectional broadcast message transmission, based on PTM, can be well achieved. In the ring network configuration, the coupling between two adjacent lasers through a partially transparent mirror induces the delay and chaotic dynamics. We prove that the dynamics is identically synchronized, and the synchronization against external perturbation also possesses good robustness; the messages introduced on the two arbitrary lasers in this ring network can be simultaneously exchanged.

Repulsive Casimir force between hyperbolic metamaterials.

The Casimir force between electric and magnetic hyperbolic metamaterial slabs is investigated. Due to hyperbolic dispersion, the electromagnetic features of these metamaterials along the optical axis are different from those perpendicular to the optical axis; consequently, these features contribute differently to the Casimir effect. The repulsive Casimir force is formed between electric and magnetic hyperbolic metamaterial slabs; moreover, hyperbolic dispersion can enhance the repulsive effect. However, by utilizing the extremely anisotropic behavior of hyperbolic metamaterials and changing the separation distance between the two slabs, the restoring Casimir force emerges. Additionally, by considering the dispersion of both the permittivity and the permeability of hyperbolic metamaterials, the Casimir force reaches several equilibrium points at different separation distances. Furthermore, the Casimir force at room temperature is discussed. Although the temperature can weaken the effect of the restoring Casimir force, stable equilibria may remain upon choosing suitable filling factors. This work shows that hyperbolic metamaterials have potential applications in micro- and nanoelectromechanical systems, especially for maintaining stability and overcoming adhesion problems.

Simultaneous trilateral communication based on three mutually coupled chaotic semiconductor lasers with optical feedback.

In this paper, we propose a chaos-based scheme allowing for trilateral communication among three mutually coupled chaotic semiconductor lasers. The coupling through a partially transparent optical mirror between two lasers induces the chaotic dynamics. We numerically solve the delay rate equations of three lasers and demonstrate that the dynamics is completely synchronous. Herein, each laser is not only a transmitter but a receiver; three different messages are encoded by simultaneously modulating bias current of the three lasers. By monitoring the synchronization error between transmitter and receiver, and comparing the error with the message of the local laser, we can decipher the message of the sender. The investigation indicates that these messages introduced on the two ends of each link among three lasers can be simultaneously transmitted and restored, so the system can realize simultaneous trilateral communication. In this scheme, an eavesdropper can monitor the synchronization error, but one has no way to obtain the bits that are being sent, so the trilateral communication is secure.

Influence of two-photon absorption on the dynamic behaviors of microring resonators.

In this paper, we have investigated the influence of two-photon absorption (TPA) on the dynamic behaviors of all-pass and add-drop microring resonators by using two iterative methods along with the linear stability analysis method. While the incident field is above a certain value, the TPA coefficient has greater influence on the steady state for all-pass and add-drop microring resonators. We use the linear stability analysis method to analyze the stability of the steady state solutions and obtain stability conditions. Results obtained have shown that the change of TPA coefficient will lead to different dynamic behaviors; in addition, while the TPA coefficient is small and its change is slight, the dynamic behaviors of the microring resonators will not change much for most regions. At last, we observe the period windows and route from chaotic to period-N in some original chaotic regions due to the fluctuation of the TPA coefficient.

Microchip dual-frequency laser with well-balanced intensity utilizing temperature control.

A continuous-wave microchip dual-frequency laser (DFL) with well balanced intensity was presented. In order to obtain such a balanced intensity distribution of the two frequency components, the DFL wavelengths were precisely tuned and spectrally matched with the emission cross section (ECS) spectrum of the gain medium by employing a temperature controller. Finally, when the heat sink temperature was controlled at -5.6°C, a 264 mW DFL signal was achieved with frequency separation at 67.52 GHz and intensity balance ratio (IBR) at 0.991.

Adipocyte enhancer binding protein 1 knockdown alleviates osteoarthritis through inhibiting NF-κB signaling pathway-mediated inflammation and extracellular matrix degradation.

Inflammation promotes the degradation of the extracellular matrix, which contributes to the development of osteoarthritis (OA). Adipocyte enhancer binding protein 1 (AEBP1) participates in multiple pathological processes related to inflammatory diseases. However, the role of AEBP1 in OA development is unknown. We found a higher AEBP1 expression in articular cartilage of OA patients (n = 20) compared to their normal controls (n = 10). Thus, we inferred that AEBP1 might affect OA progression. Then mice with destabilization of the medial meniscus (DMM) surgery and chondrocytes with IL-1ß treatment (10 ng/mL) were used to mimic OA. The increased AEBP1 expression was observed in models of OA. AEBP1 knockdown in chondrocytes reversed IL-1ß-induced inflammation and extracellular matrix degradation, which was mediated by the inactivation of NF-κB signaling pathway and the increased IκBα activity. Co-immunoprecipitation assay indicated the interaction between AEBP1 and IκBα. Importantly, IκBα knockdown depleted the protective role of AEBP1 knockdown in OA. Moreover, AEBP1 knockdown in mice with OA showed similar results to those in chondrocytes. Collectively, our findings suggest that AEBP1 knockdown alleviates the development of OA, providing a novel strategy for OA treatment.

Construction and validation of a nomogram prediction model for the progression to septic shock in elderly patients with urosepsis.

Background: Septic shock is a clinical syndrome characterized by the progression of sepsis to a severe stage. Elderly patients with urosepsis in the intensive care unit (ICU) are more likely to progress to septic shock. This study aimed to establish and validate a nomogram model for predicting the risk of progression to septic shock in elderly patients with urosepsis. Methods: We extracted data from the Medical Information Mart for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). The MIMIC-IV dataset was split into a training set for model development and an internal validation set to assess model performance. Further external validation was performed using a distinct dataset sourced from the eICU-CRD. Predictors were screened using least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression analyses. The evaluation of model performance included discrimination, calibration, and clinical usefulness. Results: The study demonstrated that the Glasgow Coma Scale (GCS), white blood count (WBC), platelet, blood urea nitrogen (BUN), calcium, albumin, congestive heart failure (CHF), and invasive ventilation were closely associated with septic shock in the training cohort. Nomogram prediction, utilizing eight parameters, demonstrated strong predictive accuracy with area under the curve (AUC) values of 0.809 (95 % CI 0.786-0.834), 0.794 (95 % CI 0.756-0.831), and 0.723 (95 % CI 0.647-0.801) in the training, internal validation, and external validation sets, respectively. Additionally, the nomogram demonstrated a promising calibration performance and significant clinical usefulness in both the training and validation sets. Conclusion: The constructed nomogram is a reliable and practical tool for predicting the risk of progression to septic shock in elderly patients with urosepsis. Its implementation in clinical practice may enhance the early identification of high-risk patients, facilitate timely and targeted interventions to mitigate the risk of septic shock, and improve patient outcomes.

The predict factors and clinical prognosis value of immune-related pneumonia of receiving PD-1 inhibitor in advanced non-small cell lung cancer: A retrospective study.

INTRODUCTION: Immune checkpoint inhibitor-associated pneumonitis (CIP) is the most common immune-related advanced event (irAE). However, the risk factors of CIP occurrence and its relationship with prognosis remain to be clarified. This study aimed to explore biomarkers, prognosis, and efficacy of CIP occurrence in non-small cell lung cancer (NSCLC) patients who received anti-PD-1 inhibitors. METHODS: We performed a retrospective study in eligible NSCLC patients treated with anti-PD-1 inhibitors in Ruijin hospital. The receiver operating characteristic (ROC) curve and logistic regression were used for the optional cut-off value and the risk of CIP, respectively. The Kaplan-Meier method and Cox hazards regression models were used for survival analyses in CIP and non-CIP groups. RESULTS: Our study enrolled 229 patients, of which 35 (15.3 %) experienced CIP. CIP patients had higher proportions of male, current and former smoking, and history of pre-existing lung diseases. CIP patients also had a higher level of WBC (p = 0.025), ANC (p = 0.020), AEC (p = 0.025), and proportion of CD4+ T lymphocytes (p = 0.033) than those in non-CIP patients. Then patients were divided into two groups according to the cutoff value. It showed high baseline proportion of CD4+ T lymphocytes (OR = 4.027 (1.279-12.677), P = 0.017) and AEC (OR = 2.697 (1.047-6.945, P = 0.040) were independent predictors of CIP occurrence. CIP occurrence was an independent predictor of progression-free survival (PFS) in the enrolled patients. Regarding patient efficacy, severe-CIP patients had the highest ORR, followed by grade 1-2 CIP patients, and non-CIP patients (44.44 %, 35.3 %, and 28.35 %, respectively). CONCLUSION: The onset time of CIP occurrence was early in severe CIP patients, suggesting the importance of early identification and timely intervention of CIP. Baseline proportion of CD4+ T lymphocytes and AEC were independent predictors of CIP occurrence. In addition, CIP occurrence predicted higher ORR, longer PFS, and more opportunities for long-term survival benefits.

Improved efficiency and stability using a novel elemental sulfur-based moving-bed denitrification process.

Elemental sulfur-based denitrification (ESDeN) technology is known as a cost-saving alternative to its heterotrophic counterpart for nutrient removal from organic-deficient water. However, the traditional fixed-bed reactor (FixBR), as an extensively used process, suffers from a low denitrification rate and even performance deterioration during long-term operation. Herein, we proposed a novel elemental sulfur-based denitrifying moving-bed reactor (ESDeN-MovBR), in which a screw rotator was employed to drive the filled sulfur particles to be microfluidized vertically (a state of vertical-loop movement). Our results showed that the ESDeN-MovBR realized much superior and more stable denitrification performance compared to the ESDeN-FixBR, as indicated by 3.09-fold higher denitrification rate and over one order of magnitude lower intermediates (NO2- and N2O) yield, which could last for over 100 days. Further research revealed that the microfluidization of sulfur particles facilitated the expelling of nitrogen bubbles and excessive biomass, resulting in the prolongation of actual hydraulic retention time by over 80 % and could partially explain the higher denitrification rate in ESDeN-MovBR. The remaining contribution to the improvement of denitrification rate was suggested to be result from changes in biofilm properties, in which the biofilm thickness of ESDeN-MovBR was found to be 3.29 times thinner yet enriched with 2.52 times more autotrophic denitrifiers. This study offered a completely new solution to boost up the denitrification performance of ESDeN technology and provided in-depth evidence for the necessity of biofilm thickness control in such technology.