Cascaded multi-phonon stimulated Raman scattering near second-harmonic generation in a thin-film lithium niobate microdisk.

High-quality microresonators can greatly enhance light-matter interactions and are excellent platforms for studying nonlinear optics. Wavelength conversion through nonlinear processes is the key to many applications of integrated optics. The stimulated Raman scattering (SRS) process can extend the emission wavelength of a laser source to a wider range. Lithium niobate (LN), as a Raman active crystalline material, has remarkable potential for wavelength conversion. Here, we demonstrate the generation of cascaded multi-phonon Raman signals near the second-harmonic generation (SHG) peak in an X-cut thin-film lithium niobate (TFLN) microdisk. Fine tuning of the specific cascaded Raman spectral lines has also been made by changing the pump wavelength. Raman lines can reach a wavelength up to about 80 nm away from the SHG signal. We realize the SFG process associated with Raman signals in the visible range as well. Our work extends the use of WGM microresonators as effective optical upconversion wavelength converters in nonlinear optical applications.

Full-color biomass carbon dots for high-level information encryption and multi-color light emitting diode applications.

Six biomass carbon dots (BCDs) with adjustable emission from 450 to 680 nm under a single wavelength excitation were successfully synthesized from spinach via solvent control strategy. The obtained BCDs show blue, green, yellow, violet, pink, and red emission with high photoluminescence quantum yield (PLQY = 12.68 ~ 30.77%). Detailed characterizations disclose that the tunable-emission mechanism is caused by the synergistic effect of carbon conjugate and surface oxidation degree. Meanwhile, full-color photoluminescence BCDs/PVP powder and BCDs/PVP/PVA films were fabricated by utilizing the prepared BCDs combined with polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA), respectively, which presented excellent high-level information encryption application. Importantly, multi-color and white light-emitting diode (LED) with Commission Internationale de L' Eclairage (CIE) of blue (0.25, 0.29); green (0.25, 0.31); yellow (0.42, 0.45); red (0.52, 0.31); and white (0.32, 0.31) were achieved by only using our prepared BCDs. This work provides a valuable strategy of preparing multi-color BCDs using readily available biomass materials and paves a way for high-level information encryption and LED applications.

Dearomative Intramolecular (4+3) Cycloadditions of Thiophenes.

Unexpectedly facile dearomative intramolecular (4+3) cycloadditions of thiophenes with epoxy enolsilanes, providing sulfur-bridged cycloadducts, are reported. A total of fifteen thiophene substrates have been found to undergo (4+3) cycloaddition smoothly to produce endo and exo (4+3) adducts in yields of up to 83 % with moderate to good diastereoselectivity. Complete conservation of enantiomeric purity was observed when the optically enriched epoxide was used. The desulfurizing transformations of the sulfur-bridged skeleton of the cycloadducts provide functionalized 6,7-fused bicyclic frameworks consisting of 1,3-cycloheptadiene subunits. Density functional theory calculations reveal the origins of the facile dearomatization of thiophenes in these (4+3) cycloadditions.

NIR-II Imaging-Guided Mitochondrial-Targeting Organic Nanoparticles for Multimodal Synergistic Tumor Therapy.

Effectively interfering energy metabolism in tumor cells and simultaneously activating the in vivo immune system to perform immune attacks are meaningful for tumor treatment. However, precisely targeted therapy is still a huge challenge. Herein, a mitochondrial-targeting phototheranostic system, FE-T nanoparticles (FE-T NPs) are developed to damage mitochondria in tumor cells and change the tumor immunosuppressive microenvironment. FE-T NPs are engineered by encapsulating the near-infrared (NIR) absorbed photosensitizer IR-FE-TPP within amphiphilic copolymer DSPE-SS-PEG-COOH for high-performing with simultaneous mitochondrial-targeting, near-infrared II (NIR-II) fluorescence imaging, and synchronous photothermal therapy (PTT) /photodynamic therapy (PDT) /immune therapy (IMT). In tumor treatment, the disulfide in the copolymer can be cleaved by excess intracellular glutathione (GSH) to release IR-FE-TPP and accumulate in mitochondria. After 808 nm irradiation, the mitochondrial localization of FE-T NPs generated reactive oxygen species (ROS), and hyperthermia, leading to mitochondrial dysfunction, photoinductive apoptosis, and immunogenic cell death (ICD). Notably, in situ enhanced PDT/PTT in vivo via mitochondrial-targeting with FE-T NPs boosts highly efficient ICD toward excellent antitumor immune response. FE-T NPs provide an effective mitochondrial-targeting phototheranostic nanoplatform for imaging-guided tumor therapy.

Numerical modeling of multi-point side-pumped mid-infrared erbium-doped fluoride fiber lasers.

We investigate the power scaling and thermal management of multi-point side-pumped 2.825 µm heavily-erbium-doped fluoride fiber lasers by numerical simulation. The 4-point (or 6-point) erbium-doped fluoride fiber laser with polished erbium-doped fluoride fiber-based side-pump couplers delivers an output laser power of over 100 W at each launched 981 nm pump power of 100 W (or 75 W). Meanwhile, the core temperature increases of the gain fiber tips are below 1 K, making it possible for a highly reflective fiber Bragg grating to work stably in high-power operation. Once the preparation processes of these erbium-doped fluoride fiber-based side-pump couplers and endcaps with effective coatings are mature, the proposed multi-point side-pumped erbium-doped fluoride fiber lasers with some feasibility may theoretically pave the way for the development of hundred-watt mid-infrared fiber lasers with effective thermal management.

Continuous renal replacement therapy with the adsorptive oXiris filter may be associated with the lower 28-day mortality in sepsis: a systematic review and meta-analysis.

BACKGROUND: The oXiris is a novel filter for continuous renal replacement therapy (CRRT) featuring an adsorption coating to adsorb endotoxins and remove inflammatory mediators. Given that no consensus has been reached on its potential benefits in treating sepsis, a meta-analysis was conducted to assess its impact on the clinical outcomes of this patient population. METHODS: Eleven databases were retrieved to find relevant observational studies and randomized controlled trials. The Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool were used to assess the quality of the included studies. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was employed to assess the certainty of evidence. The 28-day mortality was the primary outcome. Secondary outcomes were 7-, 14-, and 90-day mortality, length of intensive care unit (ICU) and hospital stay, ICU and hospital mortality, norepinephrine (NE) dose, interleukin-6 (IL-6) and lactate levels, and Sequential Organ Failure Assessment (SOFA) score. RESULTS: The meta-analysis, pooling data from 14 studies, involving 695 patients, showed significant reductions in 28-day mortality [odds ratio (OR) 0.53; 95% confidence interval (CI) 0.36-0.77, p = 0.001] and length of ICU stay [weighted mean difference (WMD) - 1.91; 95% CI - 2.56 to - 1.26, p < 0.001)] in patients with sepsis using the oXiris filter compared to other filters. Besides, the SOFA score, NE dose, IL-6 and lactate levels, and 7- and 14-day mortalities were lower in the oXiris group. However, the 90-day mortality, ICU and hospital mortality, and length of hospital stay were comparable. The quality assessment of the ten observational studies indicated intermediate to high quality (average Newcastle-Ottawa score: 7.8). However, all four randomized controlled trials (RCTs) had an unclear risk of bias. The evidence for all outcomes had a low or very low level of certainty because the original study design was mainly observational studies and the RCTs included had an unclear risk of bias and a small sample size. CONCLUSION: The treatment with the oXiris filter during CRRT in sepsis patients may be associated with lower 28-, 7-, and 14-day mortalities, lactate levels, SOFA score, NE dose, and shorter length of ICU stay. However, due to the low or very low quality of evidence, the effectiveness of oXiris filters was still uncertain. Besides, no significant difference was observed for the 90-day mortality, ICU and hospital mortality, and length of hospital stay.

A mitochondria-targeted molecular phototheranostic platform for NIR-II imaging-guided synergistic photothermal/photodynamic/immune therapy.

Phototherapy is a conducive and non-invasive strategy for cancer therapy under light irradiation. Inspiringly, fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) holds a great promise for imaging-guided phototherapy with deep penetration and high spatiotemporal resolution. However, most phototherapeutics still face great challenges, including complicated synthesis of agents, potential biotoxicity and unsatisfied therapeutic outcomes. Herein, a near-infrared laser triggered molecular photosensitizer FEPT, modified with triphenylphosphine PEGylation (PEG2000-TPP), is developed for NIR-II imaging-guided mitochondria-targeting synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/immune therapy (IMT). The mitochondria-targeting photosensitizer FEPT can produce reactive oxygen species (ROS) and hyperpyrexia upon 808 nm laser irradiation, resulting in mitochondrial dysfunction and photo-induced apoptosis via caspase-3 pathway. Phototherapy-induced hyperthermia or ROS triggers the release of immunogenic intracellular substrates from dying tumor cells, thereby promoting the activation of antitumor immunity. Herein, this work provides a practicable strategy to develop a molecular phototheranostic platform for imaging-guided cancer therapy via mitochondria-targeting.

Ectopic expression of MYB repressor GmMYB3a improves drought tolerance and productivity of transgenic peanuts (Arachis hypogaea L.) under conditions of water deficit.

Peanut is widely grown and provides protein and edible oil for millions of people. Peanut growth and productivity are frequently negatively affected by abiotic and biotic environmental factors. However, the research on improving peanut germplasm resources by genetic transformation is very limited. Here, the novel R2R3-MYB repressor GmMYB3a was introduced into peanut plants by Agrobacterium-mediated transformation for the first time for thorough evaluation of the function of GmMYB3a in drought stress plant responses. We generated GmMYB3a-transgenic peanut plants. The GmMYB3a-overexpressing lines showed significantly improved physiological responses and no yield loss non-transgenic plants, in terms of survival rates. Thus, the GmMYB3a-overexpressing plants showed better photosynthetic performance, higher relative water content, and greater water use efficiency, demonstrating their adaptive capacity to water deficit. We conclude that overexpression of GmMYB3a can improve drought tolerance and productivity in peanut.

Functional activation of a novel R2R3-MYB protein gene, GmMYB68, confers salt-alkali resistance in soybean (Glycine max L.).

Soil salinity significantly reduces soybean (Glycine max L.) production worldwide. Plants resistance to stress conditions is a complex characteristic regulated by multiple signaling pathways. The v-Myb avian myeloblastosis viral oncogene homolog (MYB) transcription factor (TF) plays a crucial role in plant development, secondary metabolism, and abiotic stress responses. GmMYB68-overexpression and RNA interference (RNAi) lines were established for examining the function of G. max GmMYB68 in plant responses to abiotic stresses. The predicted amino acid sequence of GmMYB68 was similar to that of R2R3-MYB proteins. Quantitative real-time PCR analysis revealed that GmMYB68 expression varied in response to abiotic stresses. GmMYB68-overexpression lines showed enhanced resistance to salt and alkali stresses and their osmotic adjustment and photosynthetic rates were also stronger than that of GmMYB68-RNAi and wild type plants. Although wild type and transgenic plants showed no significant differences in agronomic traits under normal conditions, the overexpression of GmMYB68 increased grain number and 100-grain weights under salt stress. Our study identified a valuable TF associated with stress response in soybean, as its overexpression might help improve salt and alkali tolerance in soybean and other crops.

Overexpression of a novel transcriptional repressor GmMYB3a negatively regulates salt-alkali tolerance and stress-related genes in soybean.

Myeloblastosis (MYB) transcription factor (TF) plays a positive role in the growth and stress response of plants; however, information on the functions of MYB repressors in soybean is limited. In the present study, the gene GmMYB3a was identified and characterized as a member of the R2R3 MYB repressor family, which is induced by various abiotic stresses. To understand the functions of GmMYB3a, a transgenic soybean over-expressing GmMYB3a was obtained and the photosynthetic index under salt-alkali treatments was evaluated. The transgenic line exhibited a series of negative regulation relative to the wild-type control. Quantitative real time polymerase chain reaction revealed that the physiological parameters, including soluble sugar, free proline, and chlorophyll contents; and photosynthetic rate decreased in the transgenic plants. Furthermore, GmMYB3a overexpression down-regulated a set of key genes associated with plant defense signal pathways. These finding suggest that GmMYB3a negatively affects the response of plants to salt stress.

Performance improvement of NOMA visible light communication system by adjusting superposition constellation: a convex optimization approach.

Non-orthogonal multiple access (NOMA) can increase the overall spectral efficiency of visible light communication (VLC) system. In this paper, we proposed a novel scheme to improve the bit error rate (BER) performance of a two-user NOMA VLC system by adjusting superposition constellation. The corresponding closed-form BER expressions are derived. Convex optimization is used to find the optimal parameters of the adjusted superposition constellation, where the overall BER is minimized. The BER performances are evaluated by theoretical analysis, Monte-Carlo (MC) simulation and experiment. The results illustrate that 8.9-dB and 8.1-dB signal-to-noise ratios (SNRs) are reduced to achieve BER of 10-3 for the two users, whose power allocation coefficients are 0.6 and 0.4, respectively.

Differential proteome association study of freeze-thaw damage in ram sperm.

In this study proteomics analysis was performed to investigate damage caused to ram sperm by the freeze-thaw process. Sperm motility, viability, reactive oxygen species (ROS) and adenosine triphosphate (ATP) content were measured to evaluate sperm quality. Compared with fresh groups, motility, viability and ATP content were all lower in freeze-thawed sperm (P < 0.001), and ROS content was higher (P < 0.001). Moreover, 25 differential protein spots were detected in two-dimensional gels using PDQuest 8.0 software and the corresponding proteins were identified using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF-TOF MS) coupled with searching of the NCBI protein sequence database. Among these proteins, hexokinase1 (HXK1), the enzyme that catalyzes the first step of glycolysis in the sperm glycolytic pathway, is known to be associated with sperm motility. Casein kinase II subunit alpha (CSNK2A2), a serine/threonine-selective protein kinase, is associated with sperm apoptosis. We used immunoblotting and immunofluorescence to analyze the expression and localization of these two proteins. HXK1 and CSNK2A2 expression levels in fresh sperm were significantly higher than that in freeze-thawed sperm (P < 0.001). HXK1 and CSNK2A2 were detected in the main part of the sperm flagellum, and the immunofluorescence signal from these proteins was weakened in the freeze-thawed group. Decreased expression of HXK1 and CSNK2A2 may be associated with decreased sperm motility and viability following freeze-thawing.

Spontaneous brain activity in patients with central retinal artery occlusion: a resting-state functional MRI study using machine learning.

Central retinal artery occlusion (CRAO) is a serious eye condition that poses a risk to vision, resulting from the blockage of the central retinal artery. Because of the anatomical connection between the ocular artery, which derives from the internal carotid artery, and the anterior middle cerebral artery, hemodynamic alterations and sudden vision loss associated with CRAO may impact brain functionality. This study aimed to examine alterations in spontaneous neural activity among patients with CRAO by resting-state functional MRI. In addition, we selected the amplitude of low-frequency fluctuation (ALFF) and fractional amplitude of low-frequency fluctuation (fALFF) values as classification features for distinguishing CRAO from healthy controls (HCs) using a support vector machine classifier. A total of 18 patients diagnosed with CRAO and 18 HCs participated in the study. Resting-state brain function images and structural images were acquired from both groups. Aberrant changes in spontaneous brain functional activity among CRAO patients were investigated utilizing ALFF and fALFF analysis methods. Group differences in ALFF/fALFF values were assessed through a two-sample t -test. Subsequently, a machine learning classifier was developed to evaluate the clinical diagnostic potential of ALFF and fALFF values. In comparison to HCs, individuals with CRAO exhibited significantly higher ALFF values in the left cerebellum_6, vermis_7, left superior frontal gyrus, and left inferior frontal gyrus, triangular part. Conversely, the CRAO group displayed notably lower ALFF values in the left precuneus and left median cingulum gyri. Furthermore, higher fALFF values were observed in the left inferior frontal gyrus, triangular part, whereas lower fALFF values were noted in the right cerebellum_Crus2, left precuneus, right angular gyrus, left angular gyrus, right supramarginal gyrus, right superior parietal gyrus, and left precuneus. Utilizing the ALFF/fALFF values, the receiver operating characteristic curves (area under the curve) yielded 0.99 and 0.94 through machine learning analysis techniques. CRAO patients exhibit atypical neural activity in the brain, characterized by ALFF and fALFF values predominantly localized in the frontal, parietal, and cerebellar regions, which are closely linked to visual cognition and motor control impairments. Furthermore, ALFF and fALFF could serve as potential neuroimaging markers beyond the orbit among CRAO.

Effectiveness of Escape Room in Medical Education: A Systematic Review and Meta-Analysis.

The primary goal of this meta-analysis is to explore the five factors of knowledge, teamwork, learning satisfaction, anxiety, and interprofessional ability to determine the value of escape rooms in medical education. Up to January 2023, we searched ScienceDirect, Scopus, PubMed, Embase, Web of Science, CNKI, and the Cochrane Library for pertinent works in either English or Chinese. The Risk of Bias 2 (RoB 2) tool and Newcastle-Ottawa Scale (NOS) were used to assess the quality of studies. Subgroup and sensitivity analyses were used to assess statistical heterogeneity, and I2 was used to measure it. Overall, escape rooms had a more significant positive effect than traditional learning on knowledge (standardized mean difference [SMD]: 0.84; 95% confidence interval [CI]: 0.36-1.33), teamwork (SMD: 4.91; 95% CI: 4.58-5.24), learning satisfaction (MD: 0.36; 95% CI: 0.08-0.64), and interprofessional ability (SMD: 1.04, 95% CI: 0.81-1.27). Moreover, the impact of escape rooms on anxiety also had significant effects (SMD: -8.23, 95% CI: -11.64 to -4.82). Escape rooms affect medical students' knowledge, teamwork, learning satisfaction, interprofessional ability, and anxiety. The findings of this study can be used as evidence that escape rooms is a more effective method than traditional teaching for improving active learning.

Exosomes: The endogenous nanomaterials packed with potential for diagnosis and treatment of neurologic disorders.

Neurologic disorders (NDs) are serious diseases that threaten public health. However, due to the complex pathogenesis and significant individual differences in traditional treatments, specific treatment methods for NDs are still lacking. Exosomes, the smallest extracellular vesicles secreted by eukaryotic cells, are receiving increasing attention in the field of NDs. They contain misfolded proteins related to various NDs, including amyloid-beta, Tau proteins, and α-synuclein, indicating their promising roles in the diagnosis and treatment of NDs. In this review, an overview of the biogenesis, composition, and biological functions of exosomes is provided. Moreover, we summarize their potential roles in the pathogenesis of three prevalent NDs (including Alzheimer's disease, Ischemic stroke, and Parkinson's disease). On this basis, the diagnostic potential and therapeutic value of exosomes carrying various bioactive molecules are discussed in detail. Also, the concerns and perspectives of exosome-based diagnosis and therapy are discussed.

Adsorption and uptake of functionalized nanoplastics (NPs) by wetland plant (Sphagnum): A unique pathway for polystyrene-NPs reduction in non-vascular plants.

Wetlands are sources and sinks for nanoplastics (NPs), where adsorption and uptake by plants constitute a crucial pathway for NPs accumulation. This study found that Sphagnum exhibited a high potential (~89.75 %) to intercept NPs despite the lack of root systems and stomata. Two pathways for 100nm polystyrene NPs accumulation in Sphagnum were located: (i) Spiral interception and foliar adsorption. Efficient adsorption is credited to the micro/nano-interlocked leaf structure, which is porous, hydrophilic and rough. (ii) Intracellular enrichment through pores. Fluorescence tracking indicates pseudo-leaves (lateral > cephalic branches) as primary organs for internalization. Accumulation of differently functionalized NPs was characterized: PS-Naked-NPs (PS), PS-COOH-NPs (PC) and PS-NH2-NPs (PN) were all largely retained by pathway (i), while pathway (ii) mainly uptake PN and PC. Unlike PS aggregation in transparent cells, PC enrichment in chloroplast cells and PN in intercellular spaces reduced pigment content and fluorescence intensity. Further, the effects of the accumulated NPs on the ecological functions of Sphagnum were evaluated. NPs reduce carbon flux (assimilation rate by 57.78 %, and respiration rate by 33.50%), significantly decreasing biomass (PS = 13.12 %, PC = 26.48 %, PN = 35.23 %). However, toxicity threshold was around 10 µg/mL, environmental levels (≤1 µg/mL) barely affected Sphagnum. This study advances understanding of the behavior and fate of NPs in non-vascular plants, and provides new perspectives for developing Sphagnum substrates for NPs interception.

Fabrication and properties of temperature-responsive imprinted sensors based on fluorescently labeled yeast cells via MVL ATRP.

Temperature-responsive yeast cell-imprinted sensors (CIPs/AuNPs/Ti3C2Tx/AuNPs/Au) were prepared based on fluorescein isothiocyanate labeled yeast cells (FITC-yeast) via metal-free visible-light-induced atom transfer radical polymerization (MVL ATRP). Here, N-isopropyl acrylamide (NIPAM) was used as a temperature-responsive functional monomer, α-methacrylic acid (MAA) was chosen as an auxiliary functional monomer, N,N'-methylene bisacrylamide (MBA) was used as a cross-linker, and FITC-yeast was selected as both a template and photocatalyst. Under the optimal conditions, the detection range of the yeast cell-imprinted sensor toward yeast cells was 1.0 × 102 to 1.0 × 109 cells per mL, and the detection limit was 11 cells per mL (S/N = 3), with a linear equation of ΔI (µA) = 8.44 log[C (cells per mL)] + 7.62 (R2 = 0.993). The sensor showed good selective recognition in the presence of interfering substances such as autolyzed yeast cells (AY), dead yeast cells (DY), human mammary epithelial cells (MCF-10A), human breast cancer cells (MCF-7) and Escherichia coli (EC). The sensor also had good consistency and reproducibility. Finally, spiked recovery experiments were performed to investigate the recognition of yeast cells in the actual sample using the yeast cell-imprinted sensor. The spiked recoveries were all in the range of 98.5-108.0%, and the RSD values were all less than 4%, indicating that the sensor had good application prospects.

Enhancing treatment performance of Chlorella pyrenoidosa on levofloxacin wastewater through microalgae-bacteria consortia: Mechanistic insights using the transcriptome.

Microalgae-bacteria consortia (MBC) system has been shown to enhance the efficiency of microalgae in wastewater treatment, yet its effectiveness in treating levofloxacin (LEV) wastewater remains unexplored. This study compared the treatment of LEV wastewater using pure Chlorella pyrenoidosa (PA) and its MBC constructed with activated sludge bacteria. The results showed that MBC improved the removal efficiency of LEV from 3.50-5.41 % to 33.62-57.20 % by enhancing the growth metabolism of microalgae. The MBC increased microalgae biomass and extracellular polymeric substance (EPS) secretion, yet reduced photosynthetic pigment content compared to the PA. At the phylum level, Proteobacteria and Actinobacteriota are the major bacteria in MBC. Furthermore, the transcriptome reveals that the growth-promoting effects of MBC are associated with the up-regulation of genes encoding the glycolysis, the citrate cycle (TCA cycle), and the pentose phosphate pathway. Enhanced carbon fixation, coupled with down-regulation of photosynthetic electron transfer processes, suggests an energy allocation mechanism within MBC. The up-regulation of porphyrin and arachidonic acid metabolism, along with the expression of genes encoding LEV-degrading enzymes, provides evidence of MBC's superior tolerance to and degradation of LEV. Overall, these findings lead to a better understanding of the underlying mechanisms through which MBC outperforms PA in treating LEV wastewater.

The relationship between the frequency of headaches associated with the personal protective equipment and its influencing factors is mediated by depression: A cross-sectional study.

Background: To evaluate the factors affecting personal protective equipment (PPE) associated with headaches in healthcare workers during the first hit of coronavirus disease 2019 (COVID-19) outbreak in China in order to provide evidence for improving the prevention and treatment of PPE-associated headaches in frontline medical personnel. Methods: In this cross-sectional study, the baseline characteristics and the prevalence of the PPE-associated headaches among frontline healthcare workers at Wuhan Taikang Hospital were objectively evaluated by means of a questionnaire survey. We obtained predictors of PPE-associated headaches frequency by multiple regression analyses. The path analysis model was applied to determine the interrelationships between the variables related to PPE-associated headaches frequency. Results: Among the 520 participants, 436 (83.85 %) reported PPE-associated headaches during the anti-epidemic period. Compare with non-PPE-associated headache, age, PHQ-9 score >10, nurses, and PSQI>5were statistically significant found in participants with PPE-associated headaches. Multivariable linear regression showed that the occupation(nurse), pre-existing primary headache diagnosis, headache intensity and depression were risk factors for the frequency of PPE-associated headaches. The path analysis model observed that direct effects from occupation (nurse), pre-existing primary headache diagnosis, headache intensity and depression on the frequency of PPE-associated headaches. Depression indirectly mediated the effects of headache intensity and sleep quality on headache frequency. (All P < 0.05). Conclusion: This study provided a path analysis model that illustrates the relationships between PPE-associated headaches frequency and its related factors among healthcare workers during the COVID-19 pandemic. It is crucial to the management of PPE-associated headaches to reduce its consequences for frontline healthcare workers.

Human patient derived organoids: an emerging precision medicine model for gastrointestinal cancer research.

Gastrointestinal cancers account for approximately one-third of the total global cancer incidence and mortality with a poor prognosis. It is one of the leading causes of cancer-related deaths worldwide. Most of these diseases lack effective treatment, occurring as a result of inappropriate models to develop safe and potent therapies. As a novel preclinical model, tumor patient-derived organoids (PDOs), can be established from patients' tumor tissue and cultured in the laboratory in 3D architectures. This 3D model can not only highly simulate and preserve key biological characteristics of the source tumor tissue in vitro but also reproduce the in vivo tumor microenvironment through co-culture. Our review provided an overview of the different in vitro models in current tumor research, the derivation of cells in PDO models, and the application of PDO model technology in gastrointestinal cancers, particularly the applications in combination with CRISPR/Cas9 gene editing technology, tumor microenvironment simulation, drug screening, drug development, and personalized medicine. It also elucidates the ethical status quo of organoid research and the current challenges encountered in clinical research, and offers a forward-looking assessment of the potential paths for clinical organoid research advancement.