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The development and application of ambient ionization and miniature mass spectrometry have become the current research hotpot, which is capable of rapid, sensitive, on-site and real-time analysis of samples without complex sample pretreatment. In this study, a rapid on-site method using dielectric barrier discharge ionization (DBDI) and a miniature mass spectrometer was developed for the screening of prohibited substances in spray cosmetics. Helium gas was used as the discharge gas and 1 mm thick quartz glass was used as the dielectric barrier in a custom-made DBDI ion source. The two brass electrodes were 10 mm apart, both mounted outside the quartz glass. The inner diameter of the glass tube at the gas inlet and outlet was 1 mm. When the experiment was carried out, the DBDI ion source was placed 3 cm in front of the discontinuous atmospheric pressure interface (DAPI) of the miniature mass spectrometer. The spray cosmetic sample was placed 8 cm directly above the plasma beam generated by the DBDI. Without any sample pretreatment, once the sample spray valve was pressed, the sample microdroplets generated in the vertical direction collided with the plasma beam generated in the horizontal direction. In the region between the DBDI and the miniature mass spectrometer, the target substances were ionized by energy and charge transfer with the plasma beam, and then detected by the miniature mass spectrometer. The helium flow rate was set at an optimum value of 220 mL/min by a gas mass flow controller. Coupled with the miniature mass spectrometer, four prohibited colorants in disposable hair dye spray and four prohibited fragrances in spray lotion were screened. Based on the observed signal-to-noise ratio (S/N) of the most intense MS/MS fragment peaks and using S/N=3 as a criterion, the limits of detection (LODs) were estimated between 10 and 50 μg/kg for the eight prohibited substances. The entire analysis procedure could be completed within 1 min. The simplified analytical protocol can effectively solve the disadvantages of traditional analytical methods that are cumbersome and time-consuming. The proposed method is simple, rapid, sensitive, efficient, and suitable for rapid on-site screening of prohibited substances in spray cosmetics.

Hyperbolic electrode linear ion trap is a good choice as the mass analyzer of miniaturized ion trap mass spectrometer for the reason that it has a compact size and excellent performance. However, ions are ejected from both opposite directions along the x-axis for existing hyperbolic electrode linear ion trap, which means that the ion detection efficiency could not be higher than 50% if only one ion detector is employed in the miniaturized ion trap mass spectrometer. This symmetrical structure significantly influences the analysis performance of hyperbolic electrode linear ion trap and limits the application at miniaturized ion trap mass spectrometer. Therefore, in order to further improve the ion detection efficiency of the ion trap, an asymmetric hyperboloid linear ion trap structure was proposed. By optimizing the unidirectional stretching distance Δra of the x-axis electrode in the direction of ion ejection after the optimization to the stretching distances Δrx of both x axis electrodes, a reasonable asymmetric radio frequency electric field was introduced for improving ion unidirectional ejection efficiency. The samples used in the simulation experiments were ions with m/z 609, 610 and 611. The internal electric field distribution, ion motion trajectory and simulated mass spectra peak of the asymmetric hyperboloid linear ion trap for different electrode structures were analyzed by simulation software SIMION and AXSIM. Then the ion unidirectional ejection efficiency and mass resolution were calculated, and the data were drawn as line charts. The simulation results showed that on the basis of the optimized symmetrical hyperboloid ion trap structure, whose x-axis electrodes were both stretched by Δrx=0.9 mm, an ion unidirectional ejection efficiency of over 90% and a mass resolution over 5 100 for m/z 610 were achieved by optimizing the parameters such as AC frequency and scanning rate, when one of the x-axis electrodes was unidirectionally stretched by Δra=0.8 mm. In addition, under the condition of ions with large m/z 1 890, a mass resolution up to 10 590 and an ion unidirectional ejection efficiency of 93.3% were achieved when Δra=0.7 mm. It proved that the asymmetric hyperboloid linear ion trap with the optimized geometric structure could greatly improve the ion detection efficiency with only one ion detector under the guarantee of high mass resolution, which had a significant advantage for developing miniaturized ion trap mass spectrometer in the future. On the whole, the research could provide a theoretical foundation for further investigations, but there were still some problems to be solved, such as the actual processing, assembly and experiment.

Abstract Background While great attention has been paid to motor and cognitive impairments in children with neonatal Hypoxic-Ischemic Encephalopathy (HIE), sleep related circadian rhythm problems, although commonly present, are often neglected. Subsequently, no early clinical indicators have been reported to correlate with sleep-related circadian dysfunction during development. Methods In this study, we first analyzed patterns of the amplitude integrated electroencephalogram (aEEG) in a cohort of newborns with various degrees of HIE. Next, during follow-ups, we collected information of sleep and circadian related problems in these patients and performed correlation analysis between aEEG parameters and different sleep/circadian disorders. Results A total of 101 neonates were included. Our results demonstrated that abnormal aEEG background pattern is significantly correlated with circadian rhythmic (r = 0.289, P = 0.01) and breathing issues during sleep (r = 0.237, P = 0.037). In contrast, the establishment of sleep–wake cycle (SWC) showed no correlation with sleep/circadian problems. Detailed analysis showed that summation of aEEG score, along with low base voltage (r = 0.272, P = 0.017 and r = -0.228, P = 0.048, respectively), correlates with sleep circadian problems. In contrast, background pattern (BP) score highly correlates with sleep breathing problem (r = 0.319, P = 0.004). Conclusion Abnormal neonatal aEEG pattern is correlated with circadian related sleep problems. Our study thus provides novel insights into predictive values of aEEG in sleep-related circadian problems in children with HIE.

Our previous studies have demonstrated that TP53-induced glycolysis and apoptosis regulator (TIGAR) can protect neurons after cerebral ischemia/reperfusion. However, the role of TIGAR in neonatal hypoxic-ischemic brain damage (HIBD) remains unknown. In the present study, 7-day-old Sprague-Dawley rat models of HIBD were established by permanent occlusion of the left common carotid artery followed by 2-hour hypoxia. At 6 days before induction of HIBD, a lentiviral vector containing short hairpin RNA of either TIGAR or gasdermin D (LV-sh_TIGAR or LV-sh_GSDMD) was injected into the left lateral ventricle and striatum. Highly aggressively proliferating immortalized (HAPI) microglial cell models of in vitro HIBD were established by 2-hour oxygen/glucose deprivation followed by 24-hour reoxygenation. Three days before in vitro HIBD induction, HAPI microglial cells were transfected with LV-sh_TIGAR or LV-sh_GSDMD. Our results showed that TIGAR expression was increased in the neonatal rat cortex after HIBD and in HAPI microglial cells after oxygen/glucose deprivation/reoxygenation. Lentivirus-mediated TIGAR knockdown in rats markedly worsened pyroptosis and brain damage after hypoxia/ischemia in vivo and in vitro. Application of exogenous nicotinamide adenine dinucleotide phosphate (NADPH) increased the NADPH level and the glutathione/oxidized glutathione ratio and decreased reactive oxygen species levels in HAPI microglial cells after oxygen/glucose deprivation/reoxygenation. Additionally, exogenous NADPH blocked the effects of TIGAR knockdown in neonatal HIBD in vivo and in vitro. These findings show that TIGAR can inhibit microglial pyroptosis and play a protective role in neonatal HIBD. The study was approved by the Animal Ethics Committee of Soochow University of China (approval No. 2017LW003) in 2017.

Circadian rhythm disorder is a common, but often neglected, consequence of neonatal hypoxic-ischemic brain damage (HIBD). However, the underlying molecular mechanisms remain largely unknown. We previously showed that, in a rat model of HIBD, up-regulation of microRNA-325 (miR-325) in the pineal gland is responsible for the suppression of Aanat, a key enzyme involved in melatonin synthesis and circadian rhythm regulation. To better understand the mechanism by which miR-325 affects circadian rhythms in neonates with HIBD, we compared clinical samples from neonates with HIBD and samples from healthy neonates recruited from the First Affiliated Hospital of Soochow University (Dushuhu Branch) in 2019. We found that circulating miR-325 levels correlated positively with the severity of sleep and circadian rhythm disorders in neonates with HIBD. Furthermore, a luciferase reporter gene assay revealed that LIM homeobox 3 (LHX3) is a novel downstream target of miR-325. In addition, in miR-325 knock-down mice, the transcription factor LHX3 exhibited an miR-325-dependent circadian pattern of expression in the pineal gland. We established a neonatal mouse model of HIBD by performing double-layer ligation of the left common carotid artery and exposing the pups to a low-oxygen environment for 2 hours. Lhx3 mRNA expression was significantly down-regulated in these mice and partially rescued in miR-325 knockout mice subjected to the same conditions. Finally, we showed that improvement in circadian rhythm-related behaviors in animals with HIBD was dependent on both miR-325 and LHX3. Taken together, our findings suggest that the miR-325-LHX3 axis is responsible for regulating circadian rhythms and provide novel insights into the identification of potential therapeutic targets for circadian rhythm disorders in patients with neonatal HIBD. The clinical trial was approved by Institutional Review Board of Children’s Hospital of Soochow University (approval No. 2015028) on July 20, 2015. Animal experiments were approved by Animal Care and Use Committee, School of Medicine, Soochow University, China (approval No. XD-2016-1) on January 15, 2016.

Objective To explore the characteristics, risk factors of postoperative infections for patients with growth hormone (GH)⁃secreting pituitary adenoma after endoscopic transsphenoidal surgery, and to share the experience of diagnosis and treatment of these patients. Methods A total of 122 patients with GH⁃secreting pituitary adenoma who underwent endoscopic transsphenoidal surgery were included from January 2016 to October 2019, and the data of postoperative body temperature, postoperative infection and related possible risk factors were analyzed. Results The incidence of postoperative infections in patients with acromegaly was significantly higher than that with other types of pituitary adenomas [9.84% (12/122) vs. 3.77% (8/212), P=0.025]. Central nervous system infection (7 cases) and bacteremia (4 cases) were the most common types of infections. Gram ⁃ negative bacilli were predominant (10 cases). The postoperative peak body temperature of patients with infections (12 cases) was significantly higher (P = 0.000) and appeared later than non ⁃infectious group (110 cases, P= 0.000). Multivariate Logistic analysis showed that intraoperative cerebrospinal fluid leakage (OR = 5.520, 95% CI:1.193-25.551; P = 0.029) and female (OR = 7.804, 95% CI: 1.088 - 55.948;P = 0.041) patients were major risk factors for postoperative infections. Conclusions For patients with GH ⁃ secreting pituitary adenoma who underwent endoscopic surgery, postoperative infections were uncommon but serious complication, especially for females, for those who experienced intraoperative cerebrospinal fluid leakage and postoperative peak body temperature delayed. Early identification and timely treatment are very important. Empirical anti ⁃ infective treatment should cover Gram ⁃ negative bacteria. Repair using autologous fat fascia and nasoseptal flap may reduce the incidence of postoperative infections in patients who suffered severe cerebrospinal fluid leakage. DOI：10.3969/j.issn.1672⁃6731.2020.03.013

Neonatal hypoxic-ischemic brain damage (HIBD) often results in various neurological deficits. Among them, a common, yet often neglected, symptom is circadian rhythm disorders. Previous studies revealed that the occurrence of cysts in the pineal gland, an organ known to regulate circadian rhythm, is associated with circadian problems in children with HIBD. However, the underlying mechanisms of pineal dependent dysfunctions post HIBD remain largely elusive. Here, by performing 10x single cell RNA sequencing, we firstly molecularly identified distinct pineal cell types and explored their transcriptome changes at single cell level at 24 and 72 h post neonatal HIBD. Bioinformatic analysis of cell prioritization showed that both subtypes of pinealocytes, the predominant component of the pineal gland, were mostly affected. We then went further to investigate how distinct pineal cell types responded to neonatal HIBD. Within pinealocytes, we revealed a molecularly defined β to α subtype conversion induced by neonatal HIBD. Within astrocytes, we discovered that all three subtypes responded to neonatal HIBD, with differential expression of reactive astrocytes markers. Two subtypes of microglia cells were both activated by HIBD, marked by up-regulation of Ccl3. Notably, microglia cells showed substantial reduction at 72 h post HIBD. Further investigation revealed that pyroptosis preferentially occurred in pineal microglia through NLRP3-Caspase-1-GSDMD signaling pathway. Taken together, our results delineated temporal changes of molecular and cellular events occurring in the pineal gland following neonatal HIBD. By revealing pyroptosis in the pineal gland, our study also provided potential therapeutic targets for preventing extravasation of pineal pathology and thus improving circadian rhythm dysfunction in neonates with HIBD.

Transient receptor potential melastatin 2 (TRPM2) is an important ion channel that represents a potential target for treating injury caused by cerebral ischemia. However, it is unclear whether reducing TRPM2 expression can help repair cerebral injury, and if so what the mechanism underlying this process involves. This study investigated the protective effect of reducing TRPM2 expression on pheochromocytoma (PC12) cells injured by oxygen-glucose deprivation (OGD). PC12 cells were transfected with plasmid encoding TRPM2 shRNAS, then subjected to OGD by incubation in glucose-free medium under hypoxic conditions for 8 hours, after which the cells were allowed to reoxygenate for 24 hours. Apoptotic cells, mitochondrial membrane potentials, reactive oxygen species levels, and cellular calcium levels were detected using flow cytometry. The relative expression of C-X-C motif chemokine ligand 2 (CXCL2), NACHT, LRR, and PYD domain–containing protein 3 (NALP3), and caspase-1 were detected using fluorescence-based quantitative reverse transcription-polymerase chain reaction and western blotting. The rates of apoptosis, mitochondrial membrane potentials, reactive oxygen species levels, and cellular calcium levels in the TRPM2-shRNA + OGD group were lower than those observed in the OGD group. Taken together, these results suggest that TRPM2 knockdown reduces OGD-induced neuronal injury, potentially by inhibiting apoptosis and reducing oxidative stress levels, mitochondrial membrane potentials, intracellular calcium concentrations, and NLRP3 inflammasome activation.

Abstract Background Previous studies have indicated edema may be involved in the pathophysiology following hypoxic-ischemic encephalopathy (HIE), and melatonin may exhibit neuro-protection against brain insults. However, little is known regarding the mechanisms that involve the protective effects of melatonin in the brain and peripheral tissues after HIE. The present study aimed to examine the effects of melatonin on multiple organs, and the expression of edema related proteins in a neonatal rat model of hypoxic-ischemic brain damage (HIBD). Methods One hundred ninety-two neonatal rats were randomly divided into three subgroups that underwent a sham surgery or HIBD. After the HIBD or sham-injury, the rats received an intraperitoneal injection of melatonin or an equal volume vehicle, respectively. We investigated the effects of melatonin on brain, kidney, and colon edema via histological examination and the expression of edema related proteins, including AQP-4, ZO-1 and occludin, via qPCR and western blot. Results Our data indicated (1) Melatonin reduced the histological injury in the brain and peripheral organs induced by HIBD as assessed via H-E staining and transmission electron microscopy. (2) Melatonin alleviated the HIBD-induced cerebral edema characterized by increased brain water content. (3) HIBD induced significant changes of edema related proteins, such as AQP-4, ZO-1 and occludin, and these changes were partially reversed by melatonin treatment. Conclusions These findings provide substantial evidence that melatonin treatment has protective effects on the brain and peripheral organs after HIBD, and the edema related proteins, AQP4, ZO-1, and occludin, may indirectly contribute tothe mechanism of the edema protection by melatonin.

Autophagy has been suggested to participate in the pathology of hypoxic-ischemic brain damage (HIBD). However, its regulatory role in HIBD remains unclear and was thus examined here using a rat model. To induce HIBD, the left common carotid artery was ligated in neonatal rats, and the rats were subjected to hypoxia for 2 hours. Some of these rats were intraperitoneally pretreated with the autophagy inhibitor 3-methyladenine (10 mM in 10 μL) or the autophagy stimulator rapamycin (1 g/kg) 1 hour before artery ligation. Our findings demonstrated that hypoxia-ischemia-induced hippocampal injury in neonatal rats was accompanied by increased expression levels of the autophagy-related proteins light chain 3 and Beclin-1 as well as of the AMPA receptor subunit GluR1, but by reduced expression of GluR2. Pretreatment with the autophagy inhibitor 3-methyladenine blocked hypoxia-ischemia-induced hippocampal injury, whereas pretreatment with the autophagy stimulator rapamycin significantly augmented hippocampal injury. Additionally, 3-methyladenine pretreatment blocked the hypoxia-ischemia-induced upregulation of GluR1 and downregulation of GluR2 in the hippocampus. By contrast, rapamycin further elevated hippocampal GluR1 levels and exacerbated decreased GluR2 expression levels in neonates with HIBD. Our results indicate that autophagy inhibition favors the prevention of HIBD in neonatal rats, at least in part, through normalizing GluR1 and GluR2 expression.

The plant embryo specific protein ATS3 is closely related to osmotic stress response in plants. Here, the stress resistance related gene OsATS was preliminarily studied in rice. Fluorescence quantitative PCR showed that the relative expression level of OsATS increased significantly after salt stress in rice. The overexpression vector of OsATS was constructed and transformed into Arabidopsis thaliana. The stress resistance test revealed that the overexpression of OsATS gene could significantly improve the salt tolerance of Arabidopsis thaliana at germination and adult stages. After that, the overexpression vector p1300-35s:OSATS and RNA interference vector pTCK303-OsATS-RNAi were transferred into rice. The stress tolerance analysis indicated that the salt tolerance of OsATS overexpression rice lines significantly increased at germination stage and seedling stage, while the salt tolerance of OsATS RNAi rice lines significantly decreased. Results of qRT-PCR and physiological index detection demonstrated that the relative expression levels of OSATS gene might regulate the protein content of proline and LEA cells by regulating the expression of OsP5CS1, OsLEA3-1 and OsPDH, thus affecting the salt tolerance in rice. This study preliminarily revealed the stress resistance function of OSATS gene, which laid a foundation for improving rice stress resistance by adjusting the relative expression level of OSATS gene. [ABSTRACT FROM AUTHOR]

Objective To summarize the clinical characteristics of Langerhans cell histiocytosis (LCH) in sellar region, to explore the indication and safety of pathological biopsy in sellar region. Methods and Results Eight patients with LCH who underwent biopsy by endoscopic transsphenoidal approach from November 2011 to November 2019 were retrospectively analyzed. The ratio of male to female was 1 : 1. The median age of 8 patients was 15.50 years old. All patients had central diabetes insipidus as the inaugural manifestation, and 7 patients had hypothalamus-related symptoms. Lesions in 7 patients involved the pituitary stalk, and in 5 patients involved the intrasellar region. The most common site of involvement was both intrasellar region and pituitary stalk (3 patients), followed by both pituitary stalk and hypothalamus (2 patients). MRI showed isointensity (8 cases) on T1WI, isointensity (6 cases), hypointensity (one case) and heterogeneous intensity (one case) on T2WI, while 6 with homogeneous enhancement and 2 with heterogeneous enhancement. The hyperintensity on T1WI of posterior pituitary was absent in all patients. The posterior pituitary bright spot was absent in all patients. Only one patient had a transient hypothalamic dysfunction after operation. None patient had cerebrospinal fluid leakage, central nervous system infection, unplanned secondary operation, death and other adverse events within one month after operation. Conclusions There were no specific clinical manifestations for LCH in sellar region, and this disease should be considered to differentiate from pituitary adenomas, germ cell tumor and lymphocytic hypophysitis. Biopsy was considered as "gold standard" for diagnosis. And biopsy by endoscopic transsphenoidal approach was a safe and reliable way for confirmation. [ABSTRACT FROM AUTHOR]

Drugs produce their therapeutic effects by modulating specific targets, and there are 89 innovative targets of first-in-class drugs approved in 2004–17, each with information about drug clinical trial dated back to 1984. Analysis of the clinical trial timelines of these targets may reveal the trial-speed differentiating features for facilitating target assessment. Here we present a comprehensive analysis of all these 89 targets, following the earlier studies for prospective prediction of clinical success of the targets of clinical trial drugs. Our analysis confirmed the literature-reported common druggability characteristics for clinical success of these innovative targets, exposed trial-speed differentiating features associated to the on-target and off-target collateral effects in humans and further revealed a simple rule for identifying the speedy human targets through clinical trials (from the earliest phase I to the 1st drug approval within 8 years). This simple rule correctly identified 75.0% of the 28 speedy human targets and only unexpectedly misclassified 13.2% of 53 non-speedy human targets. Certain extraordinary circumstances were also discovered to likely contribute to the misclassification of some human targets by this simple rule. Investigation and knowledge of trial-speed differentiating features enable prioritized drug discovery and development. [ABSTRACT FROM AUTHOR]

Objective To explore the characteristics, risk factors of postoperative infections for patients with growth hormone (GH)-secreting pituitary adenoma after endoscopic transsphenoidal surgery, and to share the experience of diagnosis and treatment of these patients. Methods A total of 122 patients with GH-secreting pituitary adenoma who underwent endoscopic transsphenoidal surgery were included from January 2016 to October 2019, and the data of postoperative body temperature, postoperative infection and related possible risk factors were analyzed. Results The incidence of postoperative infections in patients with acromegaly was significantly higher than that with other types of pituitary adenomas [9.84% (12/122) vs. 3.77% (8/212), P = 0.025]. Central nervous system infection (7 cases) and bacteremia (4 cases) were the most common types of infections. Gram-negative bacilli were predominant (10 cases). The postoperative peak body temperature of patients with infections (12 cases) was significantly higher (P = 0.000) and appeared later than non-infectious group (110 cases, P = 0.000). Multivariate Logistic analysis showed that intraoperative cerebrospinal fluid leakage (OR = 5.520, 95%CI: 1.193-25.551; P = 0.029) and female (OR = 7.804, 95% CI: 1.088-55.948; P = 0.041) patients were major risk factors for postoperative infections. Conclusions For patients with GH-secreting pituitary adenoma who underwent endoscopic surgery, postoperative infections were uncommon but serious complication, especially for females, for those who experienced intraoperative cerebrospinal fluid leakage and postoperative peak body temperature delayed. Early identification and timely treatment are very important. Empirical anti-infective treatment should cover Gram-negative bacteria. Repair using autologous fat fascia and nasoseptal flap may reduce the incidence of postoperative infections in patients who suffered severe cerebrospinal fluid leakage. [ABSTRACT FROM AUTHOR]

Objective Metastatic carcinoma in sellar region is a rare disease. This article is to discuss the metastatic origin, clinical manifestations, diagnosis and differential diagnosis of metastatic carcinoma in sellar region, and to summarize the experience in diagnosis and treatment of disease. Methods and Results From January 2014 to October 2019, six patients with metastatic carcinoma in sellar region were confirmed by pathological examinations after endoscopic or microscopic transsphenoidal surgery. Four patients presented with mass effect in sellar region as the first manifestation, and 2 patients were associated with a history of malignant neoplasm. The common clinical manifestations were headache and visual disturbance. The lesions mainly involved cavernous sinus and pituitary gland. Three patients whose lesions involved adenohypophysis presented with pituitary hypofunction, of which 2 patients were diagnosed as non-functional pituitary adenoma on admission. Conclusions Presentations associated with metastatic carcinoma in sellar region can be the first manifestation of malignant neoplasm. Compared with pituitary adenomas, metastatic carcinoma in sellar region is more prone to present with diabetes insipidus and pituitary hypofunction. Relying solely on imaging diagnosis is relatively limited, and differential diagnosis should be considered in multiple aspects to reduce the misdiagnosis rate. [ABSTRACT FROM AUTHOR]

Aim: Rapid anthropogenic warming coupled with changes in land use is altering the distributions of species, with consequences for ecosystem functioning and services. It is crucial to evaluate species range shifts based on understanding of the interaction of temperature with non‐climatic factors such as habitat availability and dispersal potential. Here, we aim to investigate roles of environmental temperature, habitat availability and population connectivity on the distributions of hard‐shore intertidal animals. We further examine potential roles of extensive artificial seawall construction in enabling poleward expansion of species in China, thus reshaping coastal biogeography. Location: Chinese coast. Time period: 2013–2017. Major taxa studied: Intertidal invertebrates. Methods: We took an integrative approach encompassing distributional ecology, thermal physiology, molecular genetics, heat budget modelling and larval dispersal to elucidate how interacting multiple drivers, including temperature, habitat availability and larval dispersal, determine distributions of hard‐shore invertebrates, focusing on what sets their range edges at a boundary between biogeographic provinces. Results: Our results untangle the complex interactions of global climate change with the impacts of regional scale coastal development. Temperature, larval transport and habitat availability are the major proximate factors controlling the range limits of coastal marine species. The artificial shorelines provide suitable habitats for hard‐shore species on the Yangtze River Delta, and minimum temperature in winter is an important factor setting the new northern range limit of these hard‐shore species along the Chinese coast. Main conclusions: In the face of global warming and global sprawl of marine hard infrastructure, species distributions, community structures and biogeographic patterns are experiencing dramatic changes. The combined influence of multiple human stressors including climate change and artificial shorelines can be evaluated by using a multidisciplinary framework, including ecological distribution, physiological sensitivity of species to these stressors, and the role of dispersal in maintaining population connectivity. [ABSTRACT FROM AUTHOR]