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Abstract The feasibility of carbon mineralization relies on the carbonation efficiency of CO2-reactive minerals, which is largely governed by the water content and state within material mesopores. Yet, the pivotal role of confined water in regulating carbonation efficiency at the nanoscale is not well understood. Here, we show that the maximum CO2 intake occurs at an optimal relative humidity (RHopt) when capillary condensation initiates within the hydrophilic mesopores. At this transition state, the pore becomes filled with metastable low-density water, providing an ideal docking site for CO2 adsorption and forming a mixed metastable state of water/CO2. We prove that RHopt depends on the mesopore size through a Kelvin-like relationship, which yields a robust engineering model to predict RHopt for realistic mineral carbonation. Building upon classical theories of phase transition in hydrophilic mesopores, this study unveils the capacity of the metastable water in CO2 intake and enhances the high-efficiency carbon mineralization with natural ore and industrial wastes in real-world applications.

AIM: To evaluate the outcomes of eye-sparing surgery for lacrimal gland adenoid cystic carcinoma and the impact on tumor recurrence and orbital integrity. METHODS: The study enrolled four patients with recurrent lacrimal gland adenoid cystic carcinoma. The outcome focused on the relevance of the integrity of the lateral orbital wall to the occurrence of extraorbital metastasis in the local recurrence of lacrimal gland adenoid cystic carcinoma. RESULTS: Three patients underwent eye-sparing surgery via lateral orbitotomy without postoperative radiotherapy, and one patient who underwent eye-sparing surgery via sub-brow approach. These four patients all demonstrated a recurrence involving the invasion of extraorbital tissues as metastatic form through surgical bone seams. CONCLUSION: Preserving intact orbital bone tissue is crucial for mitigating direct cross-organ metastasis of lacrimal gland adenoid cystic carcinoma. The findings suggest avoiding the lateral orbitotomy approach with no or limited orbital bone wall invasion.

Abstract Objective To investigate the risk factors and prognostic factors that affect the long-term clinical outcomes of acute retinal necrosis (ARN). Methods A retrospective study of patients with ARN who underwent treatment and completed follow-up in our ophthalmology department from 2011 to 2021 was conducted. The incidence and risk factors of retinal detachment (RD) and prognostic factors affecting long-term clinical outcomes, such as late-onset RD and final vision loss (

Introduction Spasticity is a common complication of stroke, which is related to poor motor recovery and limitations in the performance of activities. Both transcranial magnetic stimulation (TMS) and extracorporeal shockwave therapy (ESWT) are effective treatment methods for poststroke spasticity (PSS). However, there is no existing study exploring the safety and effectiveness of TMS combined with ESWT for PSS.Methods and analysis This study will be a prospective, single-centre, randomised, factorial, controlled clinical trial. In this trial, 136 patients with PSS will be randomly divided into 4 groups: experimental group 1 (TMS), experimental group 2 (ESWT), experimental group 3 (ESWT+TMS) and control group, 34 patients in each group; all patients received routine rehabilitation. Outcome measures will be assessed by 4 time points: baseline (T0), 2 weeks after initiation of treatment (T1), 4 weeks after initiation of treatment (T2) and follow-up (4 weeks after the end of treatment, T3). The primary outcome is the modified Ashworth scale at T2. The secondary outcomes include the modified Tardieu scale for the degree of spasticity, the Fugl-Meyer assessment scale and range of motion (ROM) for motor function, the stroke-specific quality of life scale (SS-QOL) and modified Barthel index for activities of life, cortical excitability measured by TMS–surface electromyography (EMG), cerebral cortex oxygen concentrations measured by functional near-infrared spectroscopy (fNIRS) and Hmax/Mmax ratio measured by EMG.Ethics and dissemination This study protocol was approved by the Ethics Committee of the Army Medical Center of PLA (Approval No. 2024-04) on 24 January 2024. The study will be disseminated through peer-reviewed publications and conference presentations.Trial registration number This study was registered in the Chinese Clinical Trial Registry (https://www.chictr.org.cn/; unique identifier: ChiCTR2400080862; data: 9 February 2024; study protocol V. 2.0).

Background: Pyropheophorbide-α methyl ester-mediated photodynamic therapy(MPPa-PDT) is a candidate treatment for solid tumors, including osteosarcoma. Pyroptosis has garnered significant attention in cancer research due to its pro-inflammatory and immunomodulatory nature. This study investigated the mechanism and role of MPPa-PDT-induced pyroptosis in osteosarcoma cells. Methods: We treated human osteosarcoma 143b and HOS cells with MPPa at concentrations of 0.5 μM and 0.25 μM, respectively, then irradiated the cells with LED light at 630 nm wavelength with an energy density of 4.8 J/cm2. Cell viability and apoptosis ratio were detected using CCK-8 and Annexin V–Propidium Iodide staining, respectively. Intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential (MtΔψ) were assessed using 2ʹ,7ʹ-Dichlorofluorescin diacetate, and JC-1 staining kits, respectively. Scanning Electron Microscopy (SEM) was utilized to examine cell ultrastructure. The morphological changes of the cells were observed by an inverted microscope. Western blotting analysis was conducted to measure protein levels. To elucidate the mechanism and role, we re-evaluated relevant parameters after pretreating with NAC,Si caspase-3, and Si GSDME. Results: MPPa-PDT inhibited the activity of osteosarcoma 143b and HOS cells and induced pyroptosis with mitochondrial damage, ROS aggregation, and activation of Caspase-3 and GSDME. The effects of MPPa-PDT on the activity and apoptosis of osteosarcoma cells were partially reversed after pretreating with Si GSDME. After NAC pretreatment, the activation of pyroptosis and Caspase-3 induced by MPPa-PDT was partially reversed. After Si Caspase-3 pretreatment, the pyroptosis induced by MPPa-PDT was partially reversed. Conclusion: MPPa-PDT can induce pyroptosis in osteosarcoma cells, which has the effect of enhancing apoptotic processes. Mitochondrial damage and ROS/caspase-3/GSDME pathway are the possible mechanisms of pyroptosis induced by MPPa-PDT.

Abstract Background Postoperative pulmonary complications (PPCs) after one-lung ventilation (OLV) significantly impact patient prognosis and quality of life. Objective To study the impact of an optimal inspiratory flow rate on PPCs in thoracic surgery patients. Methods One hundred eight elective thoracic surgery patients were randomly assigned to 2 groups in this consort study (control group: n = 53 with a fixed inspiratory expiratory ratio of 1:2; and experimental group [flow rate optimization group]: n = 55). Measurements of Ppeak, Pplat, PETCO2, lung dynamic compliance (Cdyn), respiratory rate, and oxygen concentration were obtained at the following specific time points: immediately after intubation (T0); immediately after starting OLV (T1); 30 min after OLV (T2); and 10 min after 2-lung ventilation (T4). The PaO2:FiO2 ratio was measured using blood gas analysis 30 min after initiating one-lung breathing (T2) and immediately when OLV ended (T3). The lung ultrasound score (LUS) was assessed following anesthesia and resuscitation (T5). The occurrence of atelectasis was documented immediately after the surgery. PPCs occurrences were noted 3 days after surgery. Results The treatment group had a significantly lower total prevalence of PPCs compared to the control group (3.64% vs. 16.98%; P = 0.022). There were no notable variations in peak airway pressure, airway plateau pressure, dynamic lung compliance, PETCO2, respiratory rate, and oxygen concentration between the two groups during intubation (T0). Dynamic lung compliance and the oxygenation index were significantly increased at T1, T2, and T4 (P

Abstract The main chemical compositions of 201 surface sediments and 53 deep sediment samples from Chaohu Lake, China, were analysed. Since the surface sediments (0–2 cm depth) in Chaohu Lake are modern sediments, this paper mainly focuses on the deep sediments (50–100 cm depth) in Chaohu Lake. Particle size analysis and magnetization determination of the CH3 and CH4 column sediment samples were carried out. The age determination data of the CH-1 column sediment samples are reported. A systematic study of the rocks and their chemical compositional characteristics in the Chaohu Lake Basin was also carried out. The results of this study show that four positive chemical weathering indicators and one negative chemical weathering indicator are applicable to the study of Chaohu Lake. The mean CIA of the Chaohu Lake sediments was less than 65, indicating that the Chaohu Lake Basin experienced weak chemical weathering and that the palaeoclimate was cold and dry. Vertical variations in the mean grain size and magnetization in the CH3 and CH4 columnar sediments reflect changes in the depositional environment and climate during deposition of the Chaohu Lake sediments. The age data from the CH-1 column sediment samples directly indicate deposition of the deep sediments in Chaohu Lake during the Little Ice Age in eastern China (AD 1380–1880). The Th/U, Sc/Th, Rb/Sr, Na2O/K2O, CaO/MgO and OC/N ratios of the Chaohu sediments reflect palaeoclimate characteristics and the chemical compositions of the source rocks in the Chaohu Lake basin. The correlations of the CIA, CIW, PIA, and CIX with the chemical compositional ratios provide information on the palaeoclimate and the distribution of the chemical compositions. The CIA, CIW, PIA, and CIX were not correlated with Cd, Pb, As, Hg, or P. In contrast, the CIA, CIW, PIA, and CIX were significantly positively correlated with Cr and N. The WIP was inconsistently correlated with the selected chemical components. Therefore, the study of the correlations of chemical weathering indicators with four heavy metals and two eutrophication-related elements is of little significance. The study of the chemical weathering characteristics of deep sediments of inland lakes should be combined with assessment of the geological characteristics of the lake basins, particularly the analysis of the chemical composition of the rocks in the lake basins.

Over the past 30 years, the survival rate for osteosarcoma (OS) has remained stagnant, indicating persistent challenges in diagnosis and treatment. Photodynamic therapy (PDT) has emerged as a novel and promising treatment modality for OS. Despite apoptosis being the primary mechanism attributed to PDT, it fails to overcome issues such as low efficacy and resistance. Ferroptosis, a Fe2+-dependent cell death process, has the potential to enhance PDT's efficacy by increasing reactive oxygen species (ROS) through the Fenton reaction. In this study, we investigated the anti-tumor mechanism of PDT and introduced an innovative therapeutic strategy that synergistically induces apoptosis and ferroptosis. Furthermore, we have identified HERC1 as a pivotal protein involved in the ubiquitination and degradation of NCOA4, while also uncovering a potential regulatory factor involving NRF2. Ultimately, by targeting the HERC1-NCOA4 axis during PDT, we successfully achieved full activation of ferroptosis, which significantly enhanced the anti-tumor efficacy of PDT. In conclusion, these findings provide new theoretical evidence for further characterizing mechanism of PDT and offer new molecular targets for the treatment of OS.

BackgroundThe COVID-19 pandemic and its economic impact have heightened the risk of mental health and pain-related issues. The integration of acupuncture with conventional medicine shows promise in improving treatment outcomes for these conditions. The Alberta Complementary Health Integration Project (ABCHIP) aimed to provide acupuncture to youth (aged 24 and under) and seniors (aged 55 and above) experiencing chronic pain, pain management issues, mental health issues, and/or related conditions. The program aimed to promote integrative care, assess the effectiveness and cost-effectiveness of these therapies, and deliver patient-centered care.DesignABCHIP provided acupuncture to address pain, mental health, and addiction issues at no cost to two vulnerable populations in Alberta: youth and the older adult. A total of 606 patients aged 14–65 received 5,424 acupuncture treatments. Outcome measures included pain interference, pain severity, sleep quality, depression, anxiety, fatigue, anger, and quality of life. Short-term outcomes were assessed through questionnaires completed at the beginning and completion of the treatments, while long-term benefits were estimated using these outcome indicators and existing literature on the economic cost of illnesses.ResultThe cost-effectiveness analysis revealed the following ratios per Quality-Adjusted Life Year (QALY): CND12,171 for the overall sample, CND10,766 for patients with pain, CND9,331 for individuals with depression, and CND9,030 for those with anxiety. The cost–benefit analysis demonstrated annual cost savings ranging from CND1,487 to CND5,255, with an average of CND3,371.ConclusionThe study findings indicate that ABCHIP’s treatment for pain, depression, anxiety, and sleep issues is cost-effective, leading to substantial cost savings and improved quality of life for patients. The program’s cost per Quality-Adjusted Life Year (QALY) is significantly lower than benchmarks used in other countries, demonstrating high cost-effectiveness and value. Patients receiving 12 treatments experienced significant improvements across all measures, with estimated economic benefits surpassing treatment costs. In summary, ABCHIP offers a cost-effective and economically efficient therapy choice for individuals dealing with pain and mental health issues.

BackgroundThis study presents real-world evidence on the clinical outcomes of the Alberta Complementary Health Integration Project (ABCHIP), which utilized acupuncture to address pain and mental health issues in two vulnerable populations in Alberta: youth (aged 24 and below) and elderly (aged 55 and above).MethodsOver 282 days, a total of 606 patients received 5,424 acupuncture treatments. Tailored to each patients’ specific pain and mental health concerns, an individualized treatment plan was selected, following a standard treatment protocol lasting 1 to 3 months. Patients were evaluated at least twice: initially and upon completing therapy. Primary treatment outcomes were assessed using various measures, including the Brief Pain Inventory (BPI), Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire 9 (PHQ9), PROMIS Anxiety 8a and its pediatric form PROMIS Anxiety-Pediatric, PROMIS Short Form v1.0 Fatigue 8a and its pediatric counterpart PROMIS Pediatric Short Form v2.0 Fatigue 10a, PROMIS Short Form v1.1 Anger 5a and its version PROMIS SF v2.0 5a, and EQ-5D-5L. These measures gauged pain reduction, improved sleep quality, reduced depression, anxiety, fatigue, anger, and quality of life, respectively.ResultsAnalysis of data from 500 patients who received at least 6 acupuncture sessions through ABCHIP showed statistically significant improvements in clinical outcomes. Among this group, the subgroup of 235 patients who received at least 12 sessions demonstrated the most favorable treatment outcomes, including an 75.5% reduction in pain severity, a 53.1% improvement in sleep quality, a 78.4% drop in depression, a 41.1% decline in anxiety, a 43.7% decrease in fatigue, a 38.2% decrease in anger, and a 42.6% improvement in overall quality of life.ConclusionIntegrating acupuncture with usual care demonstrates promise in enhancing mental health, alleviating chronic and general pain, and improving overall quality of life. The findings suggest that integrative programs, such as ABCHIP, present an effective approach to addressing pain and mental health concerns in vulnerable populations, providing valuable insights for future healthcare interventions.

BackgroundTeprotumumab, an IGF-1R monoclonal antibody, has shown significant efficacy in treating thyroid eye disease (TED). However, since teprotumumab was launched in 2020 and first approved in the United States, there were limited reports of post-marketing adverse events (AEs). In this study, we aimed to mine and analyze the AEs signals with teprotumumab on the basis of the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to provide instructions in clinical practice concerning adverse reactions and assistance in drug development and import/export into other countries.MethodsAll AE reports were obtained from the FAERS database from the first quarter of 2020 to the fourth quarter of 2023. To comprehensively analyze the AEs, we applied four disproportionality analysis algorithms, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms.ResultsA total of 687 reports from 200 patients related to administration of teprotumumab were obtained, and 78% of the cases was female. Signal detection of teprotumumab at the system organ class (SOC) level included gastrointestinal disorders, ear and labyrinth disorders, general disorders and administration site conditions, nervous system disorders, and musculoskeletal and connective tissue disorders. AEs that ranked top five at the preferred terms (PTs) level were muscle spasms, fatigue, tinnitus, headache, and deafness. The median time to those AEs onsets was 48 days (interquartile range 19.0–92.0 days) after administering drugs. Additionally, our results indicated the AEs in reproductive system and breast disorders because the prevalence of TED was more common in women.ConclusionThis study identified many AEs associated with teprotumumab and unveiled potential new AE signals. These results can provide valuable evidence for further clinical application of teprotumumab and are important in enhancing clinical medication safety.

Abstract Background Cat-scratch disease (CSD) is caused by Bartonella henselae infection. In atypical cases of CSD, pathogen determination is challenging. We report a case of Bartonella neuroretinitis with neither a clear history of scratches nor typical general symptoms. The diagnosis was made using metagenomic next-generation sequencing (mNGS), a high-throughput sequencing technology. Case presentation A female patient presented to the ophthalmologist with complaint of blurred vision in her right eye. Although with history of raising a cat, she reported no clear history of scratches or typical general symptoms, except a fever of unknown origin which resolved spontaneously. The best corrected visual acuity (BCVA) of the right eye was count fingers. Fundus examination showed optic disc oedema, macular exudates and inferior exudative retinal detachment. Laboratory examination results showed increased value of serum C-reactive protein and erythrocyte sedimentation rate. Ocular involvement of toxoplasmosis, syphilis and tuberculosis were excluded. To identify the possible causative pathogen of the disease, mNGS of aqueous humour sample was performed and 521 reads of B. henselae were identified. Serological test results further showed a positive immunoglobulin G (IgG) titre of 1:64. Taking the contact history, clinical manifestations, mNGS and serological results into consideration, the diagnosis of Bartonella neuroretinitis (ocular CSD) was made. After appropriate treatment, the BCVA of the right eye improved to 20/25 in the last follow-up. Fundus examination showed a normal optic disc and macula, and the exudates had reduced. Conclusion mNGS, a fast and unbiased method, can be used to detect B. henselae (if present) in intraocular fluid samples.; however, the results should be interpreted together with the clinical symptoms and other auxiliary test results.

Motivated by empirical observations, we proposed a possible extension of Gibrat's law. By applying it into the random growth theory of income distribution, we found that the income distribution is described by a generalized Pareto distribution (GPD) with three parameters. We observed that there is a parameter $ \eta $ in the GPD that plays a key role in determining the shape of income distribution. By using the Kolmogorov-Smirnov test, we empirically showed that, for typical market-economy countries, $ \eta $ is significantly close to 0, indicating that the income distribution is characterized by a two-class pattern: The bottom 90% of the population is approximated by an exponential distribution, while the richest 1%~3% is approximated by an asymptotic power law. However, we empirically found that in China during the period of the planned economy and the early stages of market reform (from 1978 to 1990), $ \eta $ deviated significantly from 0, indicating that the bottom of the population no longer conformed to an exponential distribution.

Abstract Tricarboxylic acid cycle (TCA cycle) plays an important role for aerobic growth of heterotrophic bacteria. Theoretically, eliminating TCA cycle would decrease carbon dissipation and facilitate chemicals biosynthesis. Here, we construct an E. coli strain without a functional TCA cycle that can serve as a versatile chassis for chemicals biosynthesis. We first use adaptive laboratory evolution to recover aerobic growth in minimal medium of TCA cycle-deficient E. coli. Inactivation of succinate dehydrogenase is a key event in the evolutionary trajectory. Supply of succinyl-CoA is identified as the growth limiting factor. By replacing endogenous succinyl-CoA dependent enzymes, we obtain an optimized TCA cycle-deficient E. coli strain. As a proof of concept, the strain is engineered for high-yield production of four separate products. This work enhances our understanding of the role of the TCA cycle in E. coli metabolism and demonstrates the advantages of using TCA cycle-deficient E. coli strain for biotechnological applications.

Abstract Existing mobile robots mostly use graph search algorithms for path planning, which suffer from relatively low planning efficiency owing to high redundancy and large computational complexity. Due to the limitations of the neighborhood search strategy, the robots could hardly obtain the most optimal global path. A global path planning algorithm, denoted as EDG*, is proposed by expanding nodes using a well-designed expanding disconnected graph operator (EDG) in this paper. Firstly, all obstacles are marked and their corners are located through the map pre-processing. Then, the EDG operator is designed to find points in non-obstruction areas to complete the rapid expansion of disconnected nodes. Finally, the EDG* heuristic iterative algorithm is proposed. It selects the candidate node through a specific valuation function and realizes the node expansion while avoiding collision with a minimum offset. Path planning experiments were conducted in a typical indoor environment and on the public dataset CSM. The result shows that the proposed EDG* reduced the planning time by more than 90% and total length of paths reduced by more than 4.6%. Compared to A*, Dijkstra and JPS, EDG* does not show an exponential explosion effect in map size. The EDG* showed better performance in terms of path smoothness, and collision avoidance. This shows that the EDG* algorithm proposed in this paper can improve the efficiency of path planning and enhance path quality.

Abstract Background This study assessed the impact of pressure-controlled ventilation (PCV) focusing on end-inspiratory flow rate on the incidence of postoperative pulmonary complications (PPCs) and inflammation levels in patients undergoing spinal surgery in the prone position. Methods A total of 187 patients who underwent posterior spinal surgery were enrolled and randomly divided into 3 groups: 61 in the volume-controlled ventilation (VCV) group (group V), 62 in the PCV-volume-guaranteed (VG) group (group P1), and 64 in the PCV-VG end-expiratory zero flow rate group (group P2). Indicators including tidal volume (VT), peak airway pressure (Ppeak), and dynamic lung compliance (Cdyn) were recorded. The Ppeak, Cdyn, PETCO2, and oxygenation index (PaO2/FiO2) after intubation (T0), after prone position (T1), 60 min after prone position (T2), and after supine position at the end of surgery (T3) of the three groups were collected. Results In the within-group comparison, compared with T0, Ppeak increased at T1 − 2 in groups V and P1 (P

Abstract Background The biosynthesis of human milk oligosaccharides (HMOs) using several microbial systems has garnered considerable interest for their value in pharmaceutics and food industries. 2′-Fucosyllactose (2′-FL), the most abundant oligosaccharide in HMOs, is usually produced using chemical synthesis with a complex and toxic process. Recombinant E. coli strains have been constructed by metabolic engineering strategies to produce 2′-FL, but the low stoichiometric yields (2′-FL/glucose or glycerol) are still far from meeting the requirements of industrial production. The sufficient carbon flux for 2′-FL biosynthesis is a major challenge. As such, it is of great significance for the construction of recombinant strains with a high stoichiometric yield. Results In the present study, we designed a 2′-FL biosynthesis pathway from fructose with a theoretical stoichiometric yield of 0.5 mol 2′-FL/mol fructose. The biosynthesis of 2′-FL involves five key enzymes: phosphomannomutase (ManB), mannose-1-phosphate guanylytransferase (ManC), GDP-d-mannose 4,6-dehydratase (Gmd), and GDP-l-fucose synthase (WcaG), and α-1,2-fucosyltransferase (FucT). Based on starting strain SG104, we constructed a series of metabolically engineered E. coli strains by deleting the key genes pfkA, pfkB and pgi, and replacing the original promoter of lacY. The co-expression systems for ManB, ManC, Gmd, WcaG, and FucT were optimized, and nine FucT enzymes were screened to improve the stoichiometric yields of 2′-FL. Furthermore, the gene gapA was regulated to further enhance 2′-FL production, and the highest stoichiometric yield (0.498 mol 2′-FL/mol fructose) was achieved by using recombinant strain RFL38 (SG104ΔpfkAΔpfkBΔpgi119-lacYΔwcaF::119-gmd-wcaG-manC-manB, 119-AGGAGGAGG-gapA, harboring plasmid P30). In the scaled-up reaction, 41.6 g/L (85.2 mM) 2′-FL was produced by a fed-batch bioconversion, corresponding to a stoichiometric yield of 0.482 mol 2′-FL/mol fructose and 0.986 mol 2′-FL/mol lactose. Conclusions The biosynthesis of 2′-FL using recombinant E. coli from fructose was optimized by metabolic engineering strategies. This is the first time to realize the biological production of 2′-FL production from fructose with high stoichiometric yields. This study also provides an important reference to obtain a suitable distribution of carbon flux between 2′-FL synthesis and glycolysis.

Asymmetric radiation in upward and downward directions supported by leaky modes can be generally exhibited in the reciprocal but geometrical up-down mirror-symmetry-breaking structures, i.e., photonic crystal slabs. Here, we theoretically propose and numerically demonstrate a scheme to break the reciprocity, and to generate and manipulate the unidirectional guided resonances (UGRs) in a one-dimensional magneto-optical (MO) grating, which radiate solely toward one side with no emission in the opposite direction. Under an external magnetic field, it is found that genuine UGRs (or quasi-UGRs) in topological nature, depicted by a phase winding number of far-field radiation, can be created by hybridizing the different orthogonal bands in such a nonreciprocal grating. We further investigate the evolution, annihilation, and band transition for residential position of UGRs in three-dimensional parameter space, and we also notice that the emission direction may be switched from one side to the other due to the tuning of the asymmetric coupling. Finally, the excitation of UGRs is examined in a lossless system related to directional coupling of external waves, and it can also be utilized to realize perfect absorption in a lossy MO grating structure under single-sided illumination. The general principles presented here may lead to an efficient and active approach for the dynamic manipulation of topological radiation asymmetry, and they may serve as new inspiration to control flexibly the resonant and topological properties of light-matter interactions.

Expansive soils are widely distributed around the world. They have significant characteristics of both hygroscopic expansion and water-loss shrinkage, which have caused serious damage to road paving, construction of low-rise houses, and construction of slopes along the banks of rivers. Similarly, the implementation of low impact development measures can cause considerable difficulties in the distribution area of expansive soil. The entire urban area of Hefei is situated on expansive soil. Although Hefei city has developed a sponge city plan, it has not been carried out on a large scale for implementation of low impact development technical measures. Experimental studies have shown that exposed expansive soils produce fissures that run up and down during wet and dry cycles. These fissures are extremely unfavorable to the infiltration of surface runoff formed by short-term heavy rainfall. This is also one of the reasons for short-term rainfall in Hefei city, resulting in serious flooding in low-lying areas with a poor drainage system. At the same time, initial rainfall is ineffective in cleaning up surface source pollution. Therefore, we can enhance the characteristics of expansive soil, keep the expansive soil unexposed, and maintain a certain level of humidity. These approaches can play a better role in the control of rainfall runoff and surface source pollution. The characteristics of expansive soils can be enhanced by mixing them with weathered sand, a physical improvement, to meet the technical requirements for infiltration, interception, and purification. It is recommended to carefully select low impact development measures in the distribution area of expansive soil to avoid the occurrence of wasteful investment and poor results.

Key Clinical Message Traditional treatment options are often insufficient in treating severe dry eyes caused by systemic diseases. This case demonstrates that ocular immersion hydrotherapy significantly alleviated symptoms and ocular surface inflammation in ocular graft‐versus‐host disease. Based on these findings, we propose it as a promising option for managing severe dry eye disease. Abstract This case report investigates the efficacy of ocular immersion hydrotherapy (OIH) in treating severe dry eye secondary to ocular graft‐versus‐host disease (oGVHD). A 35‐year‐old female with a history of acute myeloid leukemia‐M2 and subsequent hematopoietic stem cell transplantation (HSCT) developed high‐intensity oGVHD unresponsive to conventional treatments, including topical corticosteroids and lubricants. We introduced OIH, utilizing sterilized swimming goggles filled with intraocular irrigating solutions, providing a moist microenvironment for the ocular surface. Symptoms were significantly relieved after treatment. Corneal filaments and epithelial defects were significantly reduced, and in vivo confocal microscopy (IVCM) demonstrated resolution of inflammation and reappearance of corneal nerves. This case indicates that OIH could be a promising therapeutic approach for severe dry eye conditions arising from oGVHD, particularly for patients refractory to traditional treatments. Further studies are warranted to elucidate the long‐term benefits and mechanisms of OIH in oGVHD management.

Introduction: Lacrimal gland adenoid cystic carcinoma (LGACC) is characterized by a high rate of recurrence, perineural invasion, and propensity for distant metastasis, resulting in poor prognosis. This case report aimed to highlight the diagnostic and therapeutic challenges of LGACC, underscore the importance of resectioning the tumor as completely as possible for the first time, adhere to postoperative adjuvant therapy, and provide detailed insights into its surgical and diagnostic management that may not be extensively covered in large case series and meta-analyses. Case presentation: A 34-year-old man presented with progressive left eye proptosis for 4 months. Initial evaluation and imaging led to a high suspicion of LGACC, which was confirmed after an eye-sparing excision of the left orbital tumor. The patient declined to undergo postoperative radiotherapy, which was recommended after the surgery. Thus, despite surgical intervention, the patient experienced tumor recurrence 3 months post-surgery, leading to orbital exenteration. Pathological examination confirmed the presence of poorly differentiated LGACC.This time the patient underwent postoperative radiotherapy, as recommended. However, despite local control, the patient developed an intracranial metastasis within a year. Conclusion: LGACC presents significant diagnostic and therapeutic challenges owing to its insidious onset, lack of specific symptoms, and high potential for recurrence and metastasis. Thus, this case emphasizes the need for early diagnosis, aggressive treatment, and adherence to postoperative adjuvant therapy to improve patient outcomes. Future research should focus on understanding the pathogenesis of LGACC and on developing standardized diagnostic and treatment protocols to enhance patient prognosis and survival.

As an important component of lake ecosystems, plankton are often used as indicators to evaluate the health of aquatic ecosystems, such as lakes and reservoirs. The plankton integrity index (P-IBI) is a highly utilized method for evaluating the ecological health of the lakes. This study took Dianchi Lake, located in the Yangtze River Basin, as the research object and analyzed the phytoplankton, zooplankton communities, and environmental factors at 11 sampling points in this lake during the wet season (July) in 2022 and the dry season (February) in 2023. The P-IBI was established to evaluate the health status of this lake ecosystem. The results showed that a total of 83 species of phytoplankton and 31 species of zooplankton were identified in Dianchi Lake, and the number of plankton species in the dry season was significantly higher than that in the wet season. The P-IBI evaluation results for the two hydrological periods were generally “good”. Linear regression analysis showed that there was a certain negative correlation between the P-IBI value and the comprehensive trophic level index (TLI), and the evaluation results were generally in line with the actual situation of the water body. Redundancy analysis (RDA) showed that there was a significant correlation between the P-IBI and its constituent parameters and individual water quality environmental factors, such as total nitrogen (TN) and electrical conductivity (EC). In summary, by reducing errors caused by spatial and temporal changes across various hydrological periods, P-IBI represents a more scientifically rigorous technique for lake water ecological health assessments within a certain time range.

Abstract Background The characteristics of otological symptoms in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are lacking. Almost no research has been conducted to explore the emergence of otological symptoms after coronavirus disease 2019 infection. The aims of this study were to investigate the prevalence and specific clinical characteristics of and risk factors for otological symptoms among patients with SARS-CoV-2 infection. Methods We included two groups to investigate the prevalence and clinical characteristics of otological symptoms among patients with SARS-CoV-2 infection. The first sample (S1) was drawn retrospectively from four communities via questionnaires, and the second sample (S2) from an outpatient clinic. Results A total of 189 participants were included in S1 (124 women [65.6%]; mean [standard deviation (SD)] age, 33.66 [13.56] years), and 47 in S2 (25 women [53.2%]; mean [SD] age, 45.28 [14.64] years). The most prevalent otological symptoms in S1 were dizziness (15.9%), tinnitus (7.9%), aural fullness (6.9%), otalgia (5.3%), hearing loss (1.6%), and otopyorrhoea (1.1%). Moreover, for each additional typical symptom of SARS-CoV-2 infection, the risk (odds ratio) of otological symptoms increased by 1.33 (95% confidence interval: 1.10–1.61, p = 0.003). The prevalence of aural fullness was higher in the unvaccinated group than that in the group receiving two or three vaccinations (p = 0.018). Conclusions Various otological symptoms may occur in patients with SARS-CoV-2 infection. The number of typical symptoms of SARS-CoV-2 infection is positively associated with the probability of otological symptoms. However, vaccination may reduce the probability of certain otological symptoms.

Abstract To investigate the occurrence and 90-day mortality of cancer patients following unplanned admission to the intensive care unit (ICU), as well as to develop a risk prediction model for their 90-day prognosis. We prospectively analyzed data from cancer patients who were admitted to the ICU without prior planning within the past 7 days, specifically between May 12, 2021, and July 12, 2021. The patients were grouped based on their 90-day survival status, and the aim was to identify the risk factors influencing their survival status. A total of 1488 cases were included in the study, with an average age of 63.2 ± 12.4 years. The most common reason for ICU admission was sepsis (n = 940, 63.2%). During their ICU stay, 29.7% of patients required vasoactive drug support (n = 442), 39.8% needed invasive mechanical ventilation support (n = 592), and 82 patients (5.5%) received renal replacement therapy. We conducted a multivariate COX proportional hazards model analysis, which revealed that BMI and a history of hypertension were protective factors. On the other hand, antitumor treatment within the 3 months prior to admission, transfer from the emergency department, general ward, or external hospital, high APACHE score, diagnosis of shock and respiratory failure, receiving invasive ventilation, and experiencing acute kidney injury (AKI) were identified as risk factors for poor prognosis within 90 days after ICU admission. The average length of stay in the ICU was 4 days, while the hospital stay duration was 18 days. A total of 415 patients died within 90 days after ICU admission, resulting in a mortality rate of 27.9%. We selected 8 indicators to construct the predictive model, which demonstrated good discrimination and calibration. The prognosis of cancer patients who are unplanned transferred to the ICU is generally poor. Assessing the risk factors and developing a risk prediction model for these patients can play a significant role in evaluating their prognosis.

Abstract Background Viral nucleic acid testing of intraocular fluid using polymerase chain reaction (PCR) is a major laboratory examination in the diagnosis of acute retinal necrosis (ARN). Importantly, false negative PCR results may occur in several special situations. We reported a case of ARN with a negative PCR result in the aqueous humour in the very early stages of disease. Case presentation A female patient presented to the ophthalmologist with complaints of blurred vision and redness in her left eye. Her medical history included ARN in her right eye 10 years prior. Although the result of the aqueous viral analysis by PCR in her left eye was negative the first time (one day after the appearance of ocular symptoms), ARN in her left eye was presumed based on the clinical signs. With timely antiviral and anti-inflammatory treatments, the retinal lesions diminished. The viral load of herpes simplex virus (HSV) turned positive (7.25 × 103 copies/mL) one week later, increased to 2.49 × 105 copies/mL after three weeks, and finally turned negative about five weeks after the onset of disease. The initial HSV-IgG level in the aqueous humour was 0.01 U/mL and increased to 222.64 U/mL in the final sampling. Conclusions The results of PCR analysis can be negative in the very early stages of ARN. Diagnosis of ARN should be made based on the clinical features, and antiviral treatments should not be delayed. Repeated PCR analysis of the aqueous humour is necessary to confirm the diagnosis and monitor the disease process.

Abstract Mutations in Atp2b2, an outer hair cell gene, cause dominant hearing loss in humans. Using a mouse model Atp2b2 Obl/+, with a dominant hearing loss mutation (Oblivion), we show that liposome-mediated in vivo delivery of CRISPR-Cas9 ribonucleoprotein complexes leads to specific editing of the Obl allele. Large deletions encompassing the Obl locus and indels were identified as the result of editing. In vivo genome editing promotes outer hair cell survival and restores their function, leading to hearing recovery. We further show that in a double-dominant mutant mouse model, in which the Tmc1 Beethoven mutation and the Atp2b2 Oblivion mutation cause digenic genetic hearing loss, Cas9/sgRNA delivery targeting both mutations leads to partial hearing recovery. These findings suggest that liposome-RNP delivery can be used as a strategy to recover hearing with dominant mutations in OHC genes and with digenic mutations in the auditory hair cells, potentially expanding therapeutics of gene editing to treat hearing loss.

Abstract There are no Food and Drug Administration‐approved drugs for treating noise‐induced hearing loss (NIHL), reflecting the absence of clear specific therapeutic targets and effective delivery strategies. Noise trauma is demonstrated results in nicotinamide adenine dinucleotide (NAD+) downregulation and mitochondrial dysfunction in cochlear hair cells (HCs) and spiral ganglion neurons (SGNs) in mice, and NAD+ boosted by nicotinamide (NAM) supplementation maintains cochlear mitochondrial homeostasis and prevents neuroexcitatory toxic injury in vitro and ex vivo, also significantly ameliorated NIHL in vivo. To tackle the limited drug delivery efficiency due to sophisticated anatomical barriers and unique clearance pathway in ear, personalized NAM‐encapsulated porous gelatin methacryloyl (PGMA@NAM) are developed based on anatomy topography of murine temporal bone by micro‐computed tomography and reconstruction of round window (RW) niche, realizing hydrogel in situ implantation completely, NAM sustained‐release and long‐term auditory preservation in mice. This study strongly supports personalized PGMA@NAM as NIHL protection drug with effective inner ear delivery, providing new inspiration for drug‐based treatment of NIHL.

Background: This study aimed to report the clinical manifestations of presumed ocular tuberculosis (OTB) and the treatment response after anti-tuberculosis therapy (ATT) in a Chinese population. Methods: Clinical data, including general characteristics, ocular lesions, visual acuity at baseline, and final follow-up of patients with presumed OTB from 2006 to 2022 in two eye clinics in China, were retrospectively analyzed. Results: The study included 84 eyes of 52 patients. The following ocular manifestations were observed: anterior uveitis (4.8%), posterior uveitis (34.5%), panuveitis (11.9%), retinal vasculitis (40.5%) and optic neuropathy (8.3%). After ATT, the vision improved by varying degrees in 48 eyes (57.1%), remained stable in 34 eyes (40.5%) and decreased in 2 eyes (2.4%). Conclusions: OTB is likely to be misdiagnosed as other infectious uveitis and optic neuropathy. Clinical features must be interpreted in conjunction with topical and general laboratory findings and in collaboration with other subspecialties to make a final diagnosis.

Abstract R‐1,3‐butanediol (R‐1,3‐BDO) is an important chiral intermediate of penem and carbapenem synthesis. Among the different synthesis methods to obtain pure enantiomer R‐1,3‐BDO, oxidation–reduction cascades catalysed by enzymes are promising strategies for its production. Dehydrogenases have been used for the reduction step, but the enantio‐selectivity is not high enough for further organic synthesis efforts. Here, a short‐chain carbonyl reductase (LnRCR) was evaluated for the reduction step and developed via protein engineering. After docking result analysis with the substrate 4‐hydroxy‐2‐butanone (4H2B), residues were selected for virtual mutagenesis, their substrate‐binding energies were compared, and four sites were selected for saturation mutagenesis. High‐throughput screening helped identify a Ser154Lys mutant which increased the catalytic efficiency by 115% compared to the parent enzyme. Computer‐aided simulations indicated that after single residue replacement, movements in two flexible areas (VTDPAF and SVGFANK) facilitated the volumetric compression of the 4H2B‐binding pocket. The number of hydrogen bonds between the stabilized 4H2B‐binding pocket of the mutant enzyme and substrate was higher (from four to six) than the wild‐type enzyme, while the substrate‐binding energy was decreased (from −17.0 kJ/mol to −29.1 kJ/mol). Consequently, the catalytic efficiency increased by approximately 115% and enantio‐selectivity increased from 95% to 99%. Our findings indicate that compact and stable substrate‐binding pockets are critical for enzyme catalysis. Lastly, the utilization of a microbe expressing the Ser154Lys mutant enzyme was proven to be a robust process to conduct the oxidation–reduction cascade at larger scales.

Abstract Current research on autonomous mobile robots focuses primarily on perceptual accuracy and autonomous performance. In commercial and domestic constructions, concrete, wood, and glass are typically used. Laser and visual mapping or planning algorithms are highly accurate in mapping wood panels and concrete walls. However, indoor and outdoor glass curtain walls may fail to perceive these transparent materials. In this study, a novel indoor glass recognition and map optimization method based on boundary guidance is proposed. First, the status of glass recognition techniques is analyzed comprehensively. Next, a glass image segmentation network based on boundary data guidance and the optimization of a planning map based on depth repair are proposed. Finally, map optimization and path-planning tests are conducted and compared using different algorithms. The results confirm the favorable adaptability of the proposed method to indoor transparent plates and glass curtain walls. Using the proposed method, the recognition accuracy of a public test set increases to 94.1%. After adding the planning map, incorrect coverage redundancies for two test scenes reduce by 59.84% and 55.7%. Herein, a glass recognition and map optimization method is proposed that offers sufficient capacity in perceiving indoor glass materials and recognizing indoor no-entry regions.

Abstract Hearing loss (HL) can be caused by a number of different genetic factors. Non-syndromic HL refers that HL occurs as an isolated symptom in an individual, whereas syndromic HL refers that HL is associated with other symptoms or abnormalities. To date, more than 140 genes have been identified as being associated with non-syndromic HL, and approximately 400 genetic syndromes can include HL as one of the clinical symptoms. However, no gene therapeutic approaches are currently available to restore or improve hearing. Therefore, there is an urgent necessity to elucidate the possible pathogenesis of specific mutations in HL-associated genes and to investigate the promising therapeutic strategies for genetic HL. The development of the CRISPR/Cas system has revolutionized the field of genome engineering, which has become an efficacious and cost-effective tool to foster genetic HL research. Moreover, several in vivo studies have demonstrated the therapeutic efficacy of the CRISPR/Cas-mediated treatments for specific genetic HL. In this review, we briefly introduce the progress in CRISPR/Cas technique as well as the understanding of genetic HL, and then we detail the recent achievements of CRISPR/Cas technique in disease modeling and therapeutic strategies for genetic HL. Furthermore, we discuss the challenges for the application of CRISPR/Cas technique in future clinical treatments.

Photovoltaic (PV) power generation has attracted widespread interest as a clean and sustainable energy source, with increasing global attention given to renewable energy. However, the operation and monitoring of PV power generation systems often result in large amounts of data containing missing values, outliers, and noise, posing challenges for data analysis and application. Therefore, PV data cleaning plays a crucial role in ensuring data quality, enhancing data availability and reliability. This study proposes a PV data cleaning method based on Rasterized Data Image Processing (RDIP) technology, which integrates rasterization and image processing techniques to select optimal contours and extract essential data. To validate the effectiveness of our method, we conducted comparative experiments using three data cleaning methods, including our RDIP algorithm, the Pearson correlation coefficient interpolation method, and cubic spline interpolation method. Subsequently, the cleaned datasets from these methods were utilized for power prediction using two linear regression models and two neural network models. The experimental results demonstrated that data cleaned using the RDIP algorithm improved the short-term forecast accuracy by approximately 1.0% and 3.7%, respectively, compared to the other two methods, indicating the feasibility and effectiveness of the RDIP approach. However, it is worth noting that the RDIP technique has limitations due to its reliance on integer parameters for grid division, potentially leading to coarse grid divisions. Future research efforts could focus on optimizing the selection of binarization thresholds to achieve better cleaning results and exploring other potential applications of RDIP in PV data analysis.

This study retrospectively analyzes the immune and inflammatory indices of patients with lacrimal-gland benign lymphoepithelial lesion (LGBLEL) in order to screen out reference indices with higher diagnostic efficacy. The medical histories of patients whose diagnoses of LGBLEL and primary lacrimal prolapse were confirmed by pathology between August 2010 and August 2019 were collected. In the LGBLEL group, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, rheumatoid factor (RF), and immunoglobulins G, G1, G2, and G4 (IgG, IgG1, IgG2, IgG4) were higher (p < 0.05) and the expression level of C3 was lower (p < 0.05) compared to the lacrimal-gland prolapse group. Multivariate logistic regression analysis showed that IgG4, IgG, and C3 were independent risk factors for predicting LGBLEL occurrence (p < 0.05). The area under the receiver operating characteristic (ROC) curve of the prediction model (IgG4+IgG+C3) was 0.926, which was significantly better than that of any single factor. Therefore, serum levels of IgG4, IgG, and C3 were independent risk factors for predicting the occurrence of LGBLEL, and the combined diagnostic efficacy of IgG4+IgG+C3 was the highest.

Gravid female fruit flies show a strong preference to 1-octen-3-ol, a volatile compound from mango. Two odorant receptors are shown to regulate 1- octen-3-ol induced oviposition behaviour.

Abstract Background Pyrroloquinoline quinone (PQQ), a cofactor for bacterial dehydrogenases, is associated with biological processes such as mitochondriogenesis, reproduction, growth, and aging. Due to the extremely high cost of chemical synthesis and low yield of microbial synthesis, the election of effective strains and the development of dynamic fermentation strategies for enhancing PQQ production are meaningful movements to meet the large-scale industrial requirements. Results A high-titer PQQ-producing mutant strain, Hyphomicrobium denitrificans FJNU-A26, was obtained by integrating ARTP (atmospheric and room‑temperature plasma) mutagenesis, adaptive laboratory evolution and high-throughput screening strategies. Afterward, the systematic optimization of the fermentation medium was conducted using a one-factor-at-a-time strategy and response surface methodology to increase the PQQ concentration from 1.02 to 1.37 g/L. The transcriptional analysis using qRT-PCR revealed that the expression of genes involved in PQQ biosynthesis were significantly upregulated when the ARTP-ALE-derived mutant was applied. Furthermore, a novel two-stage pH control strategy was introduced to address the inconsistent effects of the pH value on cell growth and PQQ production. These combined strategies led to a 148% increase in the PQQ concentration compared with that of the initial strain FJNU-6, reaching 1.52 g/L with a yield of 40.3 mg/g DCW after 144 h of fed-batch fermentation in a 5-L fermenter. Conclusion The characteristics above suggest that FJNU-A26 represents an effective candidate as an industrial PQQ producer, and the integrated strategies can be readily extended to other microorganisms for the large-scale production of PQQ.

AIM: To investigate the value of cytokine analysis in aqueous humor (AH) for discriminating vitreoretinal lymphoma (VRL) from uveitis and for evaluating the efficacy of intravitreal methotrexate (MTX) injections. METHODS: This retrospective study was done on 28 VRL patients between 2013 and 2019. AH interleukin (IL)-10, IL-6, IL-8, vascular endothelial growth factor (VEGF), and vascular cell adhesion molecules (VCAM) were measured in 28 VRL patients and 38 uveitis patients. As to the respective examinations for distinguishing VRL from uveitis, the diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curve analysis. The response to treatment was monitored by observing changes in best-corrected visual acuity (BCVA), ocular manifestation, and AH cytokine levels in 21 patients with VRL who had undergo multiple intravitreal injections of MTX. RESULTS: Compared with uveitis patients, VRL patients had higher IL-10 level (P1.55 and 88.2% and 81.1%, respectively, for IL-10>76.7 pg/mL. In 21 patients who had undergo repeated injections, improvements in BCVA, clinical remission of VRL and continuous decrease in cytokine levels over time were observed. In those patients, the BCVA correlated with the aqueous levels of IL-10 and IL-6 during the course of disease treatment. CONCLUSION: The combination of the aqueous cytokine profiles can be instrumental for conventional diagnostic methods and for progression monitoring and treatment response.

Intermittent theta burst stimulation (iTBS), an emerging and highly efficient paradigm of repetitive transcranial magnetic stimulation (rTMS), has been demonstrated to mitigate cognitive impairment in Alzheimer's disease. Previous clinical studies have shown that the cognitive improvement of iTBS could last several weeks after treatment. Nonetheless, it is largely uncertain how the long-term effects of iTBS treatment are sustained. To investigate whether iTBS has a long-term effect on AD-type pathologies, 6-month-old APP/PS1 mice are administrated with 30 consecutive days of iTBS treatment. After a 2-month interval, morphological alterations in the brain are examined by immunohistochemistry and immunofluorescence staining, while levels of associated proteins are assessed by Western blot at the age of 9 months. We find that iTBS treatment significantly diminishes Aβ burden in the cerebral cortex and hippocampus of APP/PS1 mice. Moreover, we observe that iTBS treatment inhibits the expression of BACE1 and elevates the level of IDE, suggesting that the reduction of Aβ load could be attributed to the inhibition of Aβ production and facilitation of Aβ degradation. Furthermore, iTBS treatment attenuates neuroinflammation, neuronal apoptosis, and synaptic loss in APP/PS1 mice. Collectively, these data indicate that 1 month of iTBS treatment ameliorates pathologies in the brain of AD mice for at least 2 months. We provide the novel evidence that iTBS may exert after-effects on AD-type pathologies via inhibition of Aβ production and facilitation of Aβ degradation.

AIM: To demonstrate the clinical features, the risk factors, the visual prognosis and the recurrence of cytomegalovirus (CMV) retinitis (CMVR) in HIV-negative patients. METHODS: HIV-negative patients with CMVR were involved in this study. Best corrected visual acuity (BCVA), intraocular pressure (IOP), CMV-DNA load in aqueous and/or serum samples, treatment, follow-up time, recurrence and complications were recorded. Ocular characteristics were evaluated by fundus photographs. Association between ocular factors and visual prognosis were analyzed by regression analysis. RESULTS: Twenty-five eyes of 16 patients were included. All 25 eyes underwent intravitreal injections of anti-viral agents. The mean logMAR BCVA improved from 0.94±0.98 (0.98-0.78) initially to 0.77±0.73 (0.82-0.68) at last visit, but not significantly. After antiviral treatment, the aqueous CMV DNA load significantly reduced to (3.42±1.47)×102 copies/mL (P=0.001), compared with (2.51±3.11)×105 copies/mL at baseline. Macular involvement (R2=0.475, P=0.049) and initial visual acuity (R2=0.475, P=0.017) were significantly associated with the poor visual prognosis (BCVA

IntroductionThe retina represents a critical ocular structure. Of the various ophthalmic afflictions, retinal pathologies have garnered considerable scientific interest, owing to their elevated prevalence and propensity to induce blindness. Among clinical evaluation techniques employed in ophthalmology, optical coherence tomography (OCT) is the most commonly utilized, as it permits non-invasive, rapid acquisition of high-resolution, cross-sectional images of the retina. Timely detection and intervention can significantly abate the risk of blindness and effectively mitigate the national incidence rate of visual impairments.MethodsThis study introduces a novel, efficient global attention block (GAB) for feed forward convolutional neural networks (CNNs). The GAB generates an attention map along three dimensions (height, width, and channel) for any intermediate feature map, which it then uses to compute adaptive feature weights by multiplying it with the input feature map. This GAB is a versatile module that can seamlessly integrate with any CNN, significantly improving its classification performance. Based on the GAB, we propose a lightweight classification network model, GABNet, which we develop on a UCSD general retinal OCT dataset comprising 108,312 OCT images from 4686 patients, including choroidal neovascularization (CNV), diabetic macular edema (DME), drusen, and normal cases.ResultsNotably, our approach improves the classification accuracy by 3.7% over the EfficientNetV2B3 network model. We further employ gradient-weighted class activation mapping (Grad-CAM) to highlight regions of interest on retinal OCT images for each class, enabling doctors to easily interpret model predictions and improve their efficiency in evaluating relevant models.DiscussionWith the increasing use and application of OCT technology in the clinical diagnosis of retinal images, our approach offers an additional diagnostic tool to enhance the diagnostic efficiency of clinical OCT retinal images.

Abstract Metabolic engineering to produce tricarboxylic acid (TCA) cycle‐derived chemicals is usually associated with problems of low production yield and impaired cellular metabolism. In this work, we found that fatty acid (FA) feedstocks could enable high‐yield production of TCA cycle‐derived chemicals, while maintaining an efficient and balanced metabolic flux of the glyoxylate‐TCA cycle, which is favorable for both product synthesis and cell growth. Here, we designed a novel synthetic pathway for production of β‐alanine, an important TCA cycle‐derived product, from FAs with a high theortecial yield of 1.391 g/g. By introducing panD, improving aspA, and knocking out iclR, glyoxylate shunt was highly activated in FAs and the yield of β‐alanine reached 0.71 g/g from FAs, much higher than from glucose. Blocking the TCA cycle at icd/sucA/fumAC nodes could increase β‐alanine yield in a flask cultivation, but severely reduced cell growth and FA utilization during fed‐batch processes. Replenishing oxaloacetate by knocking out aspC and recovering fumAC could restore the growth and lead to a titer of 35.57 g/l. After relieving the oxidative stress caused by FA metabolism, β‐alanine production could reach 72.05 g/l with a maximum yield of 1.24 g/g, about 86% of the theoretical yield. Our study thus provides a promising strategy for the production of TCA cycle‐derived chemicals.

Abstract The biosynthetic investigations of microbial natural products continuously provide powerful biocatalysts for the preparation of valuable chemicals. Practical methods for preparing (S)‐3‐aminopiperidine‐2,6‐dione (2), the pharmacophore of thalidomide (1) and its analog drugs, are highly desired. To develop a biocatalyst for producing (S)‐2, we dissected the domain functions of IdgS, which is responsible for the biosynthesis of indigoidine (3), a microbial blue pigment that consists of two 2‐like moieties. Our data supported that the L‐glutamine tethered to the indigoidine assembly line is first offloaded and cyclized by the thioesterase domain to form (S)‐2, which is then dehydrogenated by the oxidation (Ox) domain and finally dimerized to yield 3. Based on this, we developed an IdgS‐derived enzyme biocatalyst, IdgS‐Ox* R539A, for preparing enantiomerically pure (S)‐2. As a proof of concept, one‐pot chemoenzymatic synthesis of 1 was achieved by combining the biocatalytic and chemical approaches.

The correlation between decentralized decision-making and swarm intelligence has emerged as a significant subject within self-organization phenomena. Here, we demonstrate that, if an exponential probability distribution of income emerges in a decentralized economic system, then the total income of all agents can be represented by an aggregate production function, in which the technology factor precisely aligns with the information content inherent in the event of decentralized decision-making by all agents. In particular, for sufficiently large population sizes, the emergence of this technology factor enables the income per capita to increase with the population size, akin to a manifestation of swarm intelligence. More importantly, we find that an exponential probability distribution of income can be generated within a peer-to-peer economy governed by specific game rules, characterizing a decentralized-decision economic system. Building upon this discovery, we propose a swarm-intelligence explanation to elucidate the transition from thousands of years of Malthusian stagnation to modern economic growth.

Abstract The cochlea consists of multiple types of cells, including hair cells, supporting cells and spiral ganglion neurons, and is responsible for converting mechanical forces into electric signals that enable hearing. Genetic and environmental factors can result in dysfunctions of cochlear and auditory systems. In recent years, gene therapy has emerged as a promising treatment in animal deafness models. One major challenge of the gene therapy for deafness is to effectively deliver genes to specific cells of cochleae. Here, we screened and identified an AAV-ie mutant, AAV-ie-K558R, that transduces hair cells and supporting cells in the cochleae of neonatal mice with high efficiency. AAV-ie-K558R is a safe vector with no obvious deficits in the hearing system. We found that AAV-ie-K558R can partially restore the hearing loss in Prestin KO mice and, importantly, deliver Atoh1 into cochlear supporting cells to generate hair cell-like cells. Our results demonstrate the clinical potential of AAV-ie-K558R for treating the hearing loss caused by hair cell death.

AIM: To investigate the clinical features of adult patients with ocular toxocariasis (OT) in north China and to diagnose adults OT patients in early stage. METHODS: Clinical data of 24 adults with OT were retrospectively analyzed. Slit lamp photographs and fundus photographs and other imaging examinations of all the patients were reviewed. A questionnaire concerning the pet ownership and place of residence was completed to investigate the possible infection origin. Descriptive statistical analyses were performed on the demographic data, clinical features, funduscopic findings and ELISA results. RESULTS: Among the 24 patients diagnosed with OT by Toxocara IgG antibody in intraocular fluid, 16 (66.7%) eyes were right eye. The onset age of 12 eyes (50.0%) was between 30 and 40 years old, and 21 (87.5%) eyes were of peripheral granuloma type. The most common sign was vitreous opacity. Granulomas were detected in all the eyes, and 20 (83.3%) patients resided in rural area. In 4 patients, the concentration of anti-Toxocara antibody both in anterior humor and in vitreous humor were detected, and the results showed the concentration in vitreous humor was much higher than aqueous humor. CONCLUSION: Our study analyzes the clinical manifestation of OT in adults, which may have been under-recognized before. Eye side, residence, and detection of granuloma may help us in diagnosis of OT in patients with monocular vitreous opacity. For adult patients with presumed OT, negative results of anti-Toxocara antibody in anterior humor cannot rule out the possibility of OT, further detection of vitreous humor is suggested for final diagnosis.

Abstract Background Transolecranon fracture-dislocation of the elbow is rarely seen in children. The purpose of this retrospective study was to discuss the pathological characteristics and treatment strategy for this injury in children. Methods From October 2016 to March 2019, 15 patients seen and treated at our institutions for transolecranon fracture-dislocation of the elbow were identified, and their medical records and radiographs were reviewed retrospectively. There were 11 boys and 4 girls, with an average age of 8.3 years (from 5 to 14 years). The left arm was involved in 10 cases, and the right arm was involved in 5 cases. Type I (simple fracture) was found in 11 cases, and type II (comminuted fracture) was found in 4 cases, 3 of which with coronoid process involved. Closed reduction was successful under local anaesthesia in 14 cases but failed in 1 case. In 11 patients with type I fractures, 10 received fixation of Kirschner wire and tension band, and one patient underwent bone plate fixation. In 4 patients with comminuted fractures (type II), internal fixation was performed with Kirschner wires combined with reconstruction plates. Results The 15 patients were followed up for 24 to 48 months (average, 30.2 months). The final evaluation showed fine anatomical relationship of the elbow in all with no complications observed. Failure of internal fixation did not occur in any patient. The fractures acquired bony union in all patients after 8 to 12 weeks (average, 9.6 weeks). The therapeutic efficacy was evaluated at the final follow-up by the Mayo elbow performance score (MEPS) as excellent in 11 cases, good in 3 cases and fair in one case. Conclusions As a type of complicated fracture-dislocation of the elbow, the transolecranon fracture-dislocation is rare in children. The fracture is mainly simple type. Treatment options depend on the type of fracture-dislocation. Only anatomical reduction of the olecranon fracture and restoration of a normal trochlear notch can lead to a stable humeroradial joint and good clinical efficacy.

Abstract The high incidence of traffic accidents brings immeasurable losses to life. In order to avoid such crises, researchers and automakers have used many methods to solve this problem. Among them, technology based on visual features is widely used in driver fatigue detection. As fatigue detection plays a vital role in the driving process, the high accuracy of fatigue monitoring is very important. This paper focuses on the method based on convolutional neural network to detect driver fatigue. First, in the face detection part, the Single‐Shot Multi‐Box Detector algorithm is used to improve the speed and accuracy of face detection to extract the eye and mouth regions; second, the VGG16 network is used to learn fatigue features, which is performed on the NTHU‐Drowsy Driver Detection (NTHU‐DDD) data set and the other two modified data sets Training test. The main result of this work is that the accuracy of fatigue monitoring is higher than other methods including the original method, with an accuracy rate of over 90%. And it has better generalization ability than the multi‐physical feature fusion detection method. At the same time, we propose the fatigue detection method based on convolutional neural network to improve the advanced driver assistance system (ADAS) to make it more robust and reliable decision making.

Abstract Background Spasticity is a common complication of intracerebral hemorrhage (ICH). However, no consensus exists on the relation between spasticity and initial clinical findings after ICH. Methods This retrospective study enrolled adult patients with a history of ICH between January 2012 and October 2020. The modified Ashworth scale was used to assess spasticity. A trained image analyst traced all ICH lesions. Multivariable logistic regression was used to examine the association between ICH lesion sites and spasticity. Results We finally analyzed 304 patients (mean age 54.86 ± 12.93 years; 72.04% men). The incidence of spasticity in patients with ICH was 30.92%. Higher National Institutes of Health stroke scale (NIHSS) scores were associated with an increased predicted probability for spasticity (odds ratio, OR = 1.153 [95% confidence interval, CI 1.093–1.216], p < .001). Logistic regression analysis revealed that lower age, higher NIHSS scores, and drinking were associated with an increased risk of moderate‐to‐severe spasticity (OR = 0.965 [95% CI 0.939–0.992], p = .013; OR = 1.068 [95% CI 1.008–1.130], p = .025; OR = 4.809 [95% CI 1.671–13.840], p = .004, respectively). However, smoking and ICH in the thalamus were associated with a reduced risk of moderate‐to‐severe spasticity (OR = 0.200 [95% CI 0.071–0.563], p = .002; OR = 0.405 [95% CI 0.140–1.174], p = .046, respectively) compared with ICH in the basal ganglia. Conclusions Our results suggest that ICH lesion locations are at least partly associated with post‐stroke spasticity rather than the latter simply being a physiological reaction to ICH itself. The predictors for spasticity after ICH were age, NIHSS scores, past medical history, and ICH lesion sites.

Nonobstructive azoospermia (NOA) refers to the failure of spermatogenesis, which affects approximately 1% of the male population and contributes to 10% of male infertility. NOA has an underlying basis of endocrine imbalances since proper human spermatogenesis relies on complex regulation and cooperation of multiple hormones. A better understanding of subtle hormonal disturbances in NOA would help design and improve hormone therapies with reduced risk in human fertility clinics. The purpose of this review is to summarize the research on the endocrinological aspects of NOA, especially the hormones involved in hypothalamic–pituitary–testis axis (HPTA), including gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, estradiol, sex hormone binding globulin, inhibin B, anti-Müllerian hormone, and leptin. For the NOA men associated with primary testicular failure, the quality of currently available evidence has not been sufficient enough to recommend any general hormone optimization therapy. Some other NOA patients, especially those with hypogonadotropic hypogonadism, could be treated with hormonal replacement. Although these approaches have succeeded in resuming the fertility in many NOA patients, the prudent strategies should be applied in individuals according to specific NOA etiology by balancing fertility benefits and potential risks. This review also discusses how NOA can be induced by immunization against hormones.

Abstract Objectives Non‐infectious uveitis is often secondary to systemic autoimmune diseases, with Behçet's disease (BD) and Vogt‐Koyanagi‐Harada disease (VKHD) as the two most common causes. Uveitis in BD and VKHD can show similar clinical manifestations, but the underlying immunopathogenesis remains unclear. Methods To understand immune landscapes in inflammatory eye tissues, we performed single‐cell RNA paired with T cell receptor (TCR) sequencing of immune cell infiltrates in aqueous humour from six patients with BD (N = 3) and VKHD (N = 3) uveitis patients. Results Although T cells strongly infiltrated in both types of autoimmune uveitis, myeloid cells only significantly presented in BD uveitis but not in VKHD uveitis. Conversely, VKHD uveitis but not BD uveitis showed an overwhelming dominance by CD4+ T cells (> 80%) within the T cell population due to expansion of CD4+ T cell clusters with effector memory (Tem) phenotypes. Correspondingly, VKHD uveitis demonstrated a selective expansion of CD4+ T cell clones which were enriched in pro‐inflammatory Granzyme H+ CD4+ Tem cluster and showed TCR and Th1 pathway activation. In contrast, BD uveitis showed a preferential expansion of CD8+ T cell clones in pro‐inflammatory Granzyme H+ CD8+ Tem cluster, and pathway activation for cytoskeleton remodelling, cellular adhesion and cytotoxicity. Conclusion Single‐cell analyses of ocular tissues reveal distinct landscapes of immune cell infiltration and T‐cell clonal expansions between VKHD and BD uveitis. Preferential involvements of pro‐inflammatory CD4+ Th1 cells in VKHD and cytotoxic CD8+ T cells in BD suggest a difference in disease immunopathogenesis and can guide precision disease management.